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Teichenné J, Tobajas Y, Leonard K, Tchoumtchoua J, Escoté X. Sustainable Polyphenol-Rich Extracts from Agricultural By-Products: Infectivity Inhibition Potential for Human Coronavirus 229E. Molecules 2025; 30:1806. [PMID: 40333750 PMCID: PMC12029669 DOI: 10.3390/molecules30081806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2025] [Revised: 04/08/2025] [Accepted: 04/15/2025] [Indexed: 05/09/2025] Open
Abstract
Polyphenol-rich extracts derived from agricultural by-products exhibit promising antiviral properties. This study evaluated the antiviral potential of extracts from red onion peels, vineyard prunings, olive prunings and chicory leaves against human coronavirus HuCoV-229E. Subcritical water extraction and resin adsorption techniques were applied to produce the extracts. The extracts were further characterised for their bioactive content, and three out of four extracts showed a high polyphenol content (>200 mg/g). The antiviral activity was assessed through viral infectivity and replication inhibition assays in human MRC-5 host cells. The results indicate that chicory leaf and red onion peel extracts demonstrated significant antiviral effects, with effective concentrations (EC50) of 61.43 µg/mL and 10.1 µg/mL, respectively. Olive pruning extract exhibited moderate activity, while vineyard pruning extract showed limited efficacy. These findings suggest that polyphenol-rich agricultural by-products could serve as sustainable sources for antiviral agents, warranting further investigation into their mechanisms of action and potential applications against other coronaviruses, including SARS-CoV-2.
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Affiliation(s)
- Joan Teichenné
- Eurecat-Centre Tecnològic de Catalunya, Unitat de Nutrició i Salut, 43204 Reus, Spain; (Y.T.); (X.E.)
| | - Yaiza Tobajas
- Eurecat-Centre Tecnològic de Catalunya, Unitat de Nutrició i Salut, 43204 Reus, Spain; (Y.T.); (X.E.)
| | - Kevin Leonard
- Biomass Valorisation Platform, Extraction Department, CELABOR Srl, 4650 Herve, Belgium; (K.L.); (J.T.)
| | - Job Tchoumtchoua
- Biomass Valorisation Platform, Extraction Department, CELABOR Srl, 4650 Herve, Belgium; (K.L.); (J.T.)
| | - Xavier Escoté
- Eurecat-Centre Tecnològic de Catalunya, Unitat de Nutrició i Salut, 43204 Reus, Spain; (Y.T.); (X.E.)
- Nutrition and Metabolic Health Research Group, Department of Biochemistry and Biotechnology, Rovira i Virgili University (URV), 43201 Reus, Spain
- Institute of Health Pere Virgili (IISPV), 43204 Reus, Spain
- Center of Environmental, Food and Toxicological Technology—TecnATox, Rovira i Virgili University, 43201 Reus, Spain
- CIBER in Physiopathology of Obesity and Nutrition (CIBEROBN), Carlos III Health Institute, 28029 Madrid, Spain
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Luong QXT, Hoang PT, Ho PT, Ayun RQ, Lee TK, Lee S. Potential Broad-Spectrum Antiviral Agents: A Key Arsenal Against Newly Emerging and Reemerging Respiratory RNA Viruses. Int J Mol Sci 2025; 26:1481. [PMID: 40003946 PMCID: PMC11855616 DOI: 10.3390/ijms26041481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2024] [Revised: 12/05/2024] [Accepted: 12/16/2024] [Indexed: 02/27/2025] Open
Abstract
Respiratory viral infections present significant global health challenges, causing substantial morbidity and mortality, particularly among highly susceptible components of the population. The emergence of pandemics and epidemics, such as those caused by influenza viruses and coronaviruses, emphasizes the urgent need for effective antiviral therapeutics. In this review, we explore the potential of broad-spectrum antiviral agents targeting respiratory RNA viruses, including influenza viruses, coronaviruses, respiratory syncytial virus, human metapneumovirus, human parainfluenza viruses, and rhinoviruses. Various broad-spectrum direct-acting and host-targeting antivirals are discussed, including monoclonal antibodies targeting conserved regions of viral surface proteins, molecules interfering with host cell receptors or viral replication machinery, viral protease inhibitors, siRNA therapies, ribonuclease, and 3D8 scFv. Advancements in host-targeting approaches to reduce resistance and RNA-based therapeutics offer significant potential for combating respiratory viral threats. Despite challenges, broad-spectrum antiviral agents represent a crucial strategy, particularly when specific viral pathogens are unidentified or rapid intervention is essential, such as during pandemics or outbreaks.
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Affiliation(s)
- Quynh Xuan Thi Luong
- Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea; (Q.X.T.L.); (P.T.H.); (P.T.H.); (R.Q.A.)
| | - Phuong Thi Hoang
- Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea; (Q.X.T.L.); (P.T.H.); (P.T.H.); (R.Q.A.)
| | - Phuong Thi Ho
- Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea; (Q.X.T.L.); (P.T.H.); (P.T.H.); (R.Q.A.)
| | - Ramadhani Qurrota Ayun
- Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea; (Q.X.T.L.); (P.T.H.); (P.T.H.); (R.Q.A.)
| | - Taek Kyun Lee
- Risk Assessment Research Center, Korea Institute of Ocean Science & Technology, Geoje 53201, Republic of Korea
| | - Sukchan Lee
- Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea; (Q.X.T.L.); (P.T.H.); (P.T.H.); (R.Q.A.)
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Paróczai D, Bikov A, Blidaru A, Bobu E, Lascu A, Mot CI, Mihaicuta S, Frent S. Comparative efficacy of repurposed drugs lopinavir-ritonavir and darunavir-ritonavir in hospitalised COVID-19 patients: insights from a tertiary centre cohort. Front Cell Infect Microbiol 2025; 14:1496176. [PMID: 39885967 PMCID: PMC11779713 DOI: 10.3389/fcimb.2024.1496176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Accepted: 12/26/2024] [Indexed: 02/01/2025] Open
Abstract
Background Drug repurposing has become a widely adopted strategy to minimise research time, costs, and associated risks. Combinations of protease inhibitors such as lopinavir and darunavir with ritonavir have been repurposed as treatments for COVID-19. Although lopinavir-ritonavir (LPV/r) and darunavir-ritonavir (DRV/r) have shown in vitro efficacy against COVID-19, the results in human studies have been inconsistent. Therefore, our objective was to compare the efficacy of LPV/r and DRV/r in COVID-19 patients admitted to a tertiary centre in Romania. Research design and methods A clinical dataset from 417 hospitalised patients was analysed. Patients were assigned to the LPV/r, DRV/r, or control (standard-of-care) group based on clinical decisions made by the attending infectious disease specialists, aligned with national treatment protocols. Kaplan-Meier and Cox proportional hazards regression analyses were conducted to compare in-hospital mortality and to identify factors associated with clinical improvement or fatal outcomes. Results By day 10, more patients showed improvement with LPV/r and DRV/r (p=0.03 and 0.01, respectively), but only LPV/r was associated with improved survival compared to the control group (p=0.05). Factors associated with mortality included male gender (HR: 3.63, p=0.02), diabetes (HR: 2.49, p=0.03), oxygen saturation below 90% at admission (HR: 5.23, p<0.01), high blood glucose levels (HR: 3.68, p=0.01), age (HR: 1.04, p=0.02), and more than 25% lesion extension on chest CT scan (HR: 2.28, p=0.03). Conclusions LPV/r, but not DRV/r, showed a survival benefit in patients hospitalised with COVID-19, but these findings deserve further investigation in a randomised clinical trial.
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Affiliation(s)
- Dóra Paróczai
- Department of Medical Microbiology, University of Szeged, Szeged, Hungary
- Albert Szent-Györgyi Health Center, Pulmonology Clinic, University of Szeged, Deszk, Hungary
| | - András Bikov
- North West Lung Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom
- Division of Immunology, Immunity to Infection and Respiratory Medicine, University of Manchester, Manchester, United Kingdom
| | - Andreea Blidaru
- Department of Infectious Diseases, Infectious Diseases and Pulmonology Clinical Hospital, Timisoara, Romania
| | - Emanuel Bobu
- Department of Pulmonology, University of Medicine and Pharmacy Timisoara, Timisoara, Romania
| | - Ana Lascu
- Department of Functional Sciences, Discipline of Pathophysiology, Centre for Translational Research and Systems Medicine, University of Medicine and Pharmacy Timisoara, Timisoara, Romania
- Institute for Cardiovascular Diseases of Timisoara, Clinic for Cardiovascular Surgery, Timisoara, Romania
| | - Cristian Ion Mot
- ENT Department, Municipal Emergency Hospital Timisoara, Timisoara, Romania
- Department of Surgery, University of Medicine and Pharmacy Timisoara, Timisoara, Romania
| | - Stefan Mihaicuta
- Department of Infectious Diseases, Infectious Diseases and Pulmonology Clinical Hospital, Timisoara, Romania
- Centre for Research and Innovation in Precision Medicine of Respiratory Diseases, Department of Pulmonology, University of Medicine and Pharmacy Timisoara, Timisoara, Romania
| | - Stefan Frent
- Department of Infectious Diseases, Infectious Diseases and Pulmonology Clinical Hospital, Timisoara, Romania
- Centre for Research and Innovation in Precision Medicine of Respiratory Diseases, Department of Pulmonology, University of Medicine and Pharmacy Timisoara, Timisoara, Romania
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Fargier PB, Damin-Pernik M, Launay M, Gagneux-Brunon A, Bellet F, Beyens MN. COVID-19 infection and risk of adverse drug reactions: Cohort study. Therapie 2025:S0040-5957(25)00002-2. [PMID: 39843284 DOI: 10.1016/j.therap.2024.12.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Revised: 12/18/2024] [Accepted: 12/31/2024] [Indexed: 01/24/2025]
Abstract
AIM During coronavirus disease 2019 (COVID-19), the incidence rate of adverse drug reactions (ADRs) in hospitalized patients seemed higher than before the pandemic. Severe inflammation triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was cited as an explanation. We aimed to determine whether COVID-19 infection was associated with a higher risk of ADRs compared to other infectious diseases. METHODS A monocentric historic cohort, "exposed/unexposed" study, was conducted in the university hospital of Saint-Étienne (inclusion period from March 05, 2020 to April 16, 2020 for "COVID-19" and from January to December 2019 for "non-COVID-19"). All ADRs reported in patients' medical records were retrospectively assessed using Bégaud et al.'s algorithm. A multivariable Cox regression was performed to assess the hazard ratio (HR). RESULTS The incidence rate of 4.64 ADRs per person-month in the "COVID-19" group did not differ from the 3.52 ADRs per person-month in the "non-COVID-19" group (multivariable adjusted HR 1.29, 95% confidence interval [CI], 0.91-1.81, P=0.1436). COVID-19 patients had more hepatobiliary disorders whereas non-COVID-19 patients had more renal and urinary disorders. Classes of drugs mostly involved in ADRs occurrence were antibiotics, followed by antithrombotics in both groups. Compared to patients with no ADR, patients with ADRs had higher C-reactive protein (CRP) levels and a lower estimated glomerular filtration rate (eGFR). CONCLUSION In this study, the incidence rate in hospitalized patients with COVID-19 was not statistically different from that in the group with another infection. High CRP levels, as well as low eGFR, were the main risk factors for the occurrence of ADRs and should be considered in further ADR prevention strategies.
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Affiliation(s)
- Paul-Benoît Fargier
- Centre régional de pharmacovigilance, hôpital Nord, CHU de Saint-Étienne, 42055 Saint-Étienne cedex, France.
| | - Marlène Damin-Pernik
- Centre régional de pharmacovigilance, hôpital Nord, CHU de Saint-Étienne, 42055 Saint-Étienne cedex, France
| | - Manon Launay
- Centre régional de pharmacovigilance, hôpital Nord, CHU de Saint-Étienne, 42055 Saint-Étienne cedex, France
| | - Amandine Gagneux-Brunon
- CIC Inserm 1408 vaccinologie, service d'infectiologie, CHU de Saint-Étienne, 42055 Saint-Étienne, France
| | - Florelle Bellet
- Centre régional de pharmacovigilance, hôpital Nord, CHU de Saint-Étienne, 42055 Saint-Étienne cedex, France
| | - Marie-Noëlle Beyens
- Centre régional de pharmacovigilance, hôpital Nord, CHU de Saint-Étienne, 42055 Saint-Étienne cedex, France
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Rath SK, Dash AK, Sarkar N, Panchpuri M. A Glimpse for the subsistence from pandemic SARS-CoV-2 infection. Bioorg Chem 2025; 154:107977. [PMID: 39603070 DOI: 10.1016/j.bioorg.2024.107977] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2024] [Revised: 11/13/2024] [Accepted: 11/15/2024] [Indexed: 11/29/2024]
Abstract
COVID-19 is an emerging viral pandemic caused by SARS-CoV-2, which is the causative agent of unprecedented disease-causing public health threats globally. Worldwide, this outbreak is wreaking havoc due to failure in risk assessment regarding the urgency of the pandemic. As per the reports, many secondary complications which include neurological, nephrological, gastrointestinal, cardiovascular, immune, and hepatic abnormalities, are linked with COVID -19 infection which is associated with prominent respiratory disorders including pneumonia. Hindering the initial binding of the virus with Angiotensin-converting enzyme 2 (ACE2) through the spike protein is one potential boulevard of monoclonal antibodies. Although some drug regimens and vaccines have shown safety in trials, none have been entirely successful yet. This review highlights, some of the potential antibodies (tocilizumab, Sarilumab, Avdoralimab, Lenzilumab, Interferon (alfa /beta /gamma)) screened against SARS-CoV-2 and the most promising drugs (Favipiravir, Hydroxychloroquine, Niclosamide, Ribavirin, Baricitinib, Remdesivir, Arbidol Losartan, Ritonavir, Lopinavir, Baloxavir, Nitazoxanide, Camostat) in various stages of development with their synthetic protocol and their clinical projects are discussed to counter COVID -19.
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Affiliation(s)
- Santosh K Rath
- School of Pharmaceuticals and Population Health Informatics, Faculty of Pharmacy, DIT University, Dehradun, Uttarakhand, 248009, India.
| | | | - Nandan Sarkar
- Department of Pharmaceutical Technology, School of Health and Medical Sciences, Adamas University, Barasat, Kolkata 700126, India
| | - Mitali Panchpuri
- School of Pharmaceuticals and Population Health Informatics, Faculty of Pharmacy, DIT University, Dehradun, Uttarakhand, 248009, India
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Helgeson SA, Mudgalkar RM, Jacobs KA, Lee AS, Sanghavi D, Moreno Franco P, Brooks IS. Association Between X/Twitter and Prescribing Behavior During the COVID-19 Pandemic: Retrospective Ecological Study. JMIR INFODEMIOLOGY 2024; 4:e56675. [PMID: 39556417 PMCID: PMC11612580 DOI: 10.2196/56675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 09/09/2024] [Accepted: 09/12/2024] [Indexed: 11/19/2024]
Abstract
BACKGROUND Social media has become a vital tool for health care providers to quickly share information. However, its lack of content curation and expertise poses risks of misinformation and premature dissemination of unvalidated data, potentially leading to widespread harmful effects due to the rapid and large-scale spread of incorrect information. OBJECTIVE We aim to determine whether social media had an undue association with the prescribing behavior of hydroxychloroquine, using the COVID-19 pandemic as the setting. METHODS In this retrospective study, we gathered the use of hydroxychloroquine in 48 hospitals in the United States between January and December 2020. Social media data from X/Twitter was collected using Brandwatch, a commercial aggregator with access to X/Twitter's data, and focused on mentions of "hydroxychloroquine" and "Plaquenil." Tweets were categorized by sentiment (positive, negative, or neutral) using Brandwatch's sentiment analysis tool, with results classified by date. Hydroxychloroquine prescription data from the National COVID Cohort Collaborative for 2020 was used. Granger causality and linear regression models were used to examine relationships between X/Twitter mentions and prescription trends, using optimum time lags determined via vector auto-regression. RESULTS A total of 581,748 patients with confirmed COVID-19 were identified. The median daily number of positive COVID-19 cases was 1318.5 (IQR 1005.75-1940.3). Before the first confirmed COVID-19 case, hydroxychloroquine was prescribed at a median rate of 559 (IQR 339.25-728.25) new prescriptions per day. A day-of-the-week effect was noted in both prescriptions and case counts. During the pandemic in 2020, hydroxychloroquine prescriptions increased significantly, with a median of 685.5 (IQR 459.75-897.25) per day, representing a 22.6% rise from baseline. The peak occurred on April 2, 2020, with 3411 prescriptions, a 397.6% increase. Hydroxychloroquine mentions on X/Twitter peaked at 254,770 per day on April 5, 2020, compared to a baseline of 9124 mentions per day before January 21, 2020. During this study's period, 3,823,595 total tweets were recorded, with 10.09% (n=386,115) positive, 37.87% (n=1,448,030) negative, and 52.03% (n=1,989,450) neutral sentiments. A 1-day lag was identified as the optimal time for causal association between tweets and hydroxychloroquine prescriptions. Univariate analysis showed significant associations across all sentiment types, with the largest impact from positive tweets. Multivariate analysis revealed only neutral and negative tweets significantly affected next-day prescription rates. CONCLUSIONS During the first year of the COVID-19 pandemic, there was a significant association between X/Twitter mentions and the number of prescriptions of hydroxychloroquine. This study showed that X/Twitter has an association with the prescribing behavior of hydroxychloroquine. Clinicians need to be vigilant about their potential unconscious exposure to social media as a source of medical knowledge, and health systems and organizations need to be more diligent in identifying expertise, source, and quality of evidence when shared on social media platforms.
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Affiliation(s)
- Scott A Helgeson
- Department of Pulmonary and Critical Care Medicine, Mayo Clinic, Jacksonville, FL, United States
| | - Rohan M Mudgalkar
- School of Information Sciences, Center for Health Informatics, University of Illinois at Urbana-Champaign, Ubana-Champaign, IL, United States
| | - Keith A Jacobs
- School of Information Sciences, Center for Health Informatics, University of Illinois at Urbana-Champaign, Ubana-Champaign, IL, United States
| | - Augustine S Lee
- Department of Pulmonary and Critical Care Medicine, Mayo Clinic, Jacksonville, FL, United States
| | - Devang Sanghavi
- Department of Critical Care Medicine, Mayo Clinic, Jacksonville, FL, United States
| | - Pablo Moreno Franco
- Department of Transplant Medicine, Mayo Clinic, Jacksonville, FL, United States
| | - Ian S Brooks
- School of Information Sciences, Center for Health Informatics, University of Illinois at Urbana-Champaign, Ubana-Champaign, IL, United States
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Wu Y, Wu Z, Jin Q, Liu J, Xu P. Identification and Analysis of Biomarkers Associated with Lipophagy and Therapeutic Agents for COVID-19. Viruses 2024; 16:923. [PMID: 38932215 PMCID: PMC11209609 DOI: 10.3390/v16060923] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 05/28/2024] [Accepted: 06/04/2024] [Indexed: 06/28/2024] Open
Abstract
BACKGROUND Lipids, as a fundamental cell component, play an regulating role in controlling the different cellular biological processes involved in viral infections. A notable feature of coronavirus disease 2019 (COVID-19) is impaired lipid metabolism. The function of lipophagy-related genes in COVID-19 is unknown. The present study aimed to investigate biomarkers and drug targets associated with lipophagy and lipophagy-based therapeutic agents for COVID-19 through bioinformatics analysis. METHODS Lipophagy-related biomarkers for COVID-19 were identified using machine learning algorithms such as random forest, Support Vector Machine-Recursive Feature Elimination, Generalized Linear Model, and Extreme Gradient Boosting in three COVID-19-associated GEO datasets: scRNA-seq (GSE145926) and bulk RNA-seq (GSE183533 and GSE190496). The cMAP database was searched for potential COVID-19 medications. RESULTS The lipophagy pathway was downregulated, and the lipid droplet formation pathway was upregulated, resulting in impaired lipid metabolism. Seven lipophagy-related genes, including ACADVL, HYOU1, DAP, AUP1, PRXAB2, LSS, and PLIN2, were used as biomarkers and drug targets for COVID-19. Moreover, lipophagy may play a role in COVID-19 pathogenesis. As prospective drugs for treating COVID-19, seven potential downregulators (phenoxybenzamine, helveticoside, lanatoside C, geldanamycin, loperamide, pioglitazone, and trichostatin A) were discovered. These medication candidates showed remarkable binding energies against the seven biomarkers. CONCLUSIONS The lipophagy-related genes ACADVL, HYOU1, DAP, AUP1, PRXAB2, LSS, and PLIN2 can be used as biomarkers and drug targets for COVID-19. Seven potential downregulators of these seven biomarkers may have therapeutic effects for treating COVID-19.
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Affiliation(s)
- Yujia Wu
- Institute of Tropical Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, China; (Y.W.); (Z.W.); (Q.J.)
| | - Zhenlin Wu
- Institute of Tropical Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, China; (Y.W.); (Z.W.); (Q.J.)
| | - Qiying Jin
- Institute of Tropical Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, China; (Y.W.); (Z.W.); (Q.J.)
| | - Jinyuan Liu
- Basic Medical College, Guangzhou University of Chinese Medicine, Guangzhou 510405, China;
| | - Peiping Xu
- Institute of Tropical Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, China; (Y.W.); (Z.W.); (Q.J.)
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Lü Z, Dai X, Xu J, Liu Z, Guo Y, Gao Z, Meng F. Medicinal chemistry strategies toward broad-spectrum antiviral agents to prevent next pandemics. Eur J Med Chem 2024; 271:116442. [PMID: 38685143 DOI: 10.1016/j.ejmech.2024.116442] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Revised: 04/02/2024] [Accepted: 04/19/2024] [Indexed: 05/02/2024]
Abstract
The pandemic and tremendous impact of severe acute respiratory syndrome coronavirus 2 alert us, despite great achievements in prevention and control of infectious diseases, we still lack universal and powerful antiviral strategies to rapidly respond to the potential threat of serious infectious disease. Various highly contagious and pathogenic viruses, as well as other unknown viruses may appear or reappear in human society at any time, causing a catastrophic epidemic. Developing broad-spectrum antiviral drugs with high security and efficiency is of great significance for timely meeting public health emergency and protecting the lives and health of the people. Hence, in this review, we summarized diverse broad-spectrum antiviral targets and corresponding agents from a medicinal chemistry prospective, compared the pharmacological advantages and disadvantages of different targets, listed representative agents, showed their structures, pharmacodynamics and pharmacokinetics characteristics, and conducted a critical discussion on their development potential, in the hope of providing up-to-date guidance for the development of broad-spectrum antivirals and perspectives for applications of antiviral therapy.
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Affiliation(s)
- Zirui Lü
- State Key Laboratory of NBC Protection for Civilian, Beijing, 102205, China
| | - Xiandong Dai
- State Key Laboratory of NBC Protection for Civilian, Beijing, 102205, China
| | - Jianjie Xu
- State Key Laboratory of NBC Protection for Civilian, Beijing, 102205, China
| | - Zhenming Liu
- State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, China
| | - Yongbiao Guo
- State Key Laboratory of NBC Protection for Civilian, Beijing, 102205, China
| | - Zhenhua Gao
- State Key Laboratory of NBC Protection for Civilian, Beijing, 102205, China
| | - Fanhua Meng
- State Key Laboratory of NBC Protection for Civilian, Beijing, 102205, China.
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Lei J, Qiu P, Wu Z, Ding A, Hu J, Hou J, Jiang Y, Pu H, Huang Q, Zhang X, Li B, Wang X, Ye K, Xu Z, Lu X. Integrative multi-omics analyses reveal vesicle transport as a potential target for thoracic aortic aneurysm. Comput Biol Med 2024; 170:108071. [PMID: 38325212 DOI: 10.1016/j.compbiomed.2024.108071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 12/21/2023] [Accepted: 01/27/2024] [Indexed: 02/09/2024]
Abstract
BACKGROUND Thoracic aortic aneurysm (TAA) refers to dilation and enlargement of the thoracic aorta caused by various reasons. Most patients have no apparent symptoms in the early stage and are subject to a poor prognosis once the aneurysm ruptures. It is crucial to identify individuals who are predisposed to TAA and to discover effective therapeutic targets for early intervention. METHODS We conducted a label-free quantitative proteomic analysis among aorta tissue samples from TAA patients to screen differentially expressed proteins (DEPs) and key co-expression modules. Two datasets from Gene Expression Omnibus (GEO) database were included for integrative analysis, and the identified genes were subjected to immunohistochemistry (IHC) validation. Detailed vesicle transport related enrichment analysis was conducted and two FDA-approved drugs, chlorpromazine (CPZ) and chloroquine (CQ), were selected for in vivo inhibition of vesicle transport in mice TAA model. The diameter of thoracic aorta, mortality and histological differences after interventions were evaluated. RESULTS We found significant enrichments in functions involved with vesicle transport, extracellular matrix organizing, and infection diseases in TAA. Endocytosis was the most essential vesicle transport process in TAA formation. Interventions with CPZ and CQ significantly reduced the aneurysm diameter and elastin degradation in vivo and enhanced the survival rates of TAA mice. CONCLUSIONS We systematically screened the aberrantly regulated bioprocesses in TAA based on integrative multi-omics analyses, identified and demonstrated the importance of vesicle transport in the TAA formation. Our study provided pilot evidence that vesicular transport was a potential and promising target for the treatment of TAA.
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Affiliation(s)
- Jiahao Lei
- Department of Vascular Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China; Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Peng Qiu
- Department of Vascular Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
| | - Zhaoyu Wu
- Department of Vascular Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
| | - Angang Ding
- Department of Ultrasound, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
| | - Jiateng Hu
- Department of Vascular Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
| | - Jingli Hou
- Instrumental analysis center, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Yihong Jiang
- Department of Vascular Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
| | - Hongji Pu
- Department of Vascular Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
| | - Qun Huang
- Department of Vascular Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
| | - Xing Zhang
- Department of Vascular Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
| | - Bo Li
- Department of Vascular Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
| | - Xin Wang
- Department of Vascular Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
| | - Kaichuang Ye
- Department of Vascular Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
| | - Zhijue Xu
- Department of Vascular Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China; Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China.
| | - Xinwu Lu
- Department of Vascular Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
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10
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Chaudhury S, Kaur P, Gupta D, Anand P, Chaudhary M, Tiwari S, Mittal A, Gupta J, Kaur S, Singh VD, Dhawan D, Singh P, Sahu SK. Therapeutic Management with Repurposing Approaches: A Mystery During COVID-19 Outbreak. Curr Mol Med 2024; 24:712-733. [PMID: 37312440 DOI: 10.2174/1566524023666230613141746] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 02/10/2023] [Accepted: 02/13/2023] [Indexed: 06/15/2023]
Abstract
The ubiquitous pandemic that emerged due to COVID-19 affected the whole planet. People all over the globe became vulnerable to the unpredictable emergence of coronavirus. The sudden emergence of respiratory disease in coronavirus infected several patients. This affected human life drastically, from mild symptoms to severe illness, leading to mortality. COVID-19 is an exceptionally communicable disease caused by SARS-CoV-2. According to a genomic study, the viral spike RBD interactions with the host ACE2 protein from several coronavirus strains and the interaction between RBD and ACE2 highlighted the potential change in affinity from the virus causing the COVID-19 outbreak to a progenitor type of SARS-CoV-2. SARS-CoV-2, which could be the principal reservoir, is phylogenetically related to the SARS-like bat virus. Other research works reported that intermediary hosts for the transmission of viruses to humans could include cats, bats, snakes, pigs, ferrets, orangutans, and monkeys. Even with the arrival of vaccines and individuals getting vaccinated and treated with FDAapproved repurposed drugs like Remdesivir, the first and foremost steps aimed towards the possible control and minimization of community transmission of the virus include social distancing, self-realization, and self-health care. In this review paper, we discussed and summarized various approaches and methodologies adopted and proposed by researchers all over the globe to help with the management of this zoonotic outbreak by following repurposed approaches.
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Affiliation(s)
- Soumik Chaudhury
- School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar-Delhi G.T. Road, Phagwara, 144411, Punjab, India
| | - Paranjeet Kaur
- School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar-Delhi G.T. Road, Phagwara, 144411, Punjab, India
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Deepali Gupta
- School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar-Delhi G.T. Road, Phagwara, 144411, Punjab, India
| | - Palak Anand
- School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar-Delhi G.T. Road, Phagwara, 144411, Punjab, India
| | - Manish Chaudhary
- School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar-Delhi G.T. Road, Phagwara, 144411, Punjab, India
| | - Siddhita Tiwari
- School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar-Delhi G.T. Road, Phagwara, 144411, Punjab, India
| | - Amit Mittal
- Faculty of Pharmaceutical Sciences, Desh Bhagat University, Amloh Road, Mandi Gobindgarh, 147301, Punjab, India
| | - Jeena Gupta
- School of Bioscience, Lovely Professional University, Jalandhar-Delhi G.T. Road, Phagwara, 144411, Punjab, India
| | - Sukhmeen Kaur
- Department of Opthalmology, Punjab Institute of Medical Sciences, Jalandhar, 144001, Punjab, India
| | - Varsh Deep Singh
- American University of Barbados, Wildey, St. Michael, BB11100, Barbados
| | - Dakshita Dhawan
- School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar-Delhi G.T. Road, Phagwara, 144411, Punjab, India
| | - Princejyot Singh
- School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar-Delhi G.T. Road, Phagwara, 144411, Punjab, India
| | - Sanjeev Kumar Sahu
- School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar-Delhi G.T. Road, Phagwara, 144411, Punjab, India
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11
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Ding C, Chen Y, Miao G, Qi Z. Research Advances on the Role of Lipids in the Life Cycle of Human Coronaviruses. Microorganisms 2023; 12:63. [PMID: 38257890 PMCID: PMC10820681 DOI: 10.3390/microorganisms12010063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 12/23/2023] [Accepted: 12/27/2023] [Indexed: 01/24/2024] Open
Abstract
Coronaviruses (CoVs) are emerging pathogens with a significant potential to cause life-threatening harm to human health. Since the beginning of the 21st century, three highly pathogenic and transmissible human CoVs have emerged, triggering epidemics and posing major threats to global public health. CoVs are enveloped viruses encased in a lipid bilayer. As fundamental components of cells, lipids can play an integral role in many physiological processes, which have been reported to play important roles in the life cycle of CoVs, including viral entry, uncoating, replication, assembly, and release. Therefore, research on the role of lipids in the CoV life cycle can provide a basis for a better understanding of the infection mechanism of CoVs and provide lipid targets for the development of new antiviral strategies. In this review, research advances on the role of lipids in different stages of viral infection and the possible targets of lipids that interfere with the viral life cycle are discussed.
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Affiliation(s)
- Cuiling Ding
- Department of Microbiology, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, China; (C.D.); (Y.C.)
| | - Yibo Chen
- Department of Microbiology, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, China; (C.D.); (Y.C.)
| | - Gen Miao
- Department of Nutrition and Food Hygiene, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, China;
| | - Zhongtian Qi
- Department of Microbiology, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, China; (C.D.); (Y.C.)
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12
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Arman BY, Brun J, Hill ML, Zitzmann N, von Delft A. An Update on SARS-CoV-2 Clinical Trial Results-What We Can Learn for the Next Pandemic. Int J Mol Sci 2023; 25:354. [PMID: 38203525 PMCID: PMC10779148 DOI: 10.3390/ijms25010354] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 12/21/2023] [Accepted: 12/24/2023] [Indexed: 01/12/2024] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has claimed over 7 million lives worldwide, providing a stark reminder of the importance of pandemic preparedness. Due to the lack of approved antiviral drugs effective against coronaviruses at the start of the pandemic, the world largely relied on repurposed efforts. Here, we summarise results from randomised controlled trials to date, as well as selected in vitro data of directly acting antivirals, host-targeting antivirals, and immunomodulatory drugs. Overall, repurposing efforts evaluating directly acting antivirals targeting other viral families were largely unsuccessful, whereas several immunomodulatory drugs led to clinical improvement in hospitalised patients with severe disease. In addition, accelerated drug discovery efforts during the pandemic progressed to multiple novel directly acting antivirals with clinical efficacy, including small molecule inhibitors and monoclonal antibodies. We argue that large-scale investment is required to prepare for future pandemics; both to develop an arsenal of broad-spectrum antivirals beyond coronaviruses and build worldwide clinical trial networks that can be rapidly utilised.
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Affiliation(s)
- Benediktus Yohan Arman
- Antiviral Drug Discovery Unit, Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK; (J.B.); (N.Z.)
- Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford OX1 3QU, UK
| | - Juliane Brun
- Antiviral Drug Discovery Unit, Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK; (J.B.); (N.Z.)
- Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford OX1 3QU, UK
| | - Michelle L. Hill
- Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK;
| | - Nicole Zitzmann
- Antiviral Drug Discovery Unit, Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK; (J.B.); (N.Z.)
- Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford OX1 3QU, UK
| | - Annette von Delft
- Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford OX1 3QU, UK
- Centre for Medicine Discovery, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK
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13
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Vieux N, Perrier Q, Bedouch P, Epaulard O. Much ado about nothing? Discrepancy between the available data on the antiviral effect of hydroxychloroquine in March 2020 and its inclusion in COVID-19 clinical trials and outpatient prescriptions. Public Health 2023; 225:35-44. [PMID: 37918175 DOI: 10.1016/j.puhe.2023.09.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Revised: 07/10/2023] [Accepted: 09/24/2023] [Indexed: 11/04/2023]
Abstract
OBJECTIVES Many of the 2020 COVID-19 clinical trials included an (hydroxy)chloroquine ((H)CQ) arm. We aimed to juxtapose the state of science before April 2020 regarding the benefits of (H)CQ for viral infections with the number and size of the clinical trials studying (H)CQ and the volume of (H)CQ dispensed in France. STUDY DESIGN We identified and analysed published scientific material regarding the antiviral activity of (H)CQ and publicly available data regarding clinical trials and drug dispensation in France. METHODS We conducted a review of scientific publications available before April 2020 and a systematic analysis of COVID-19 clinical trials featuring (H)CQ registered on clinicaltrials.gov. RESULTS Before April 2020, 894 scientific publications mentioning (H)CQ for viruses other than coronaviruses were available, including 35 in vitro studies (reporting an inconstant inhibition of viral replication), 11 preclinical studies (reporting no or disputable positive effects), and 32 clinical trials (reporting no or disputable positive effects). Moreover, 67 publications on (H)CQ and coronavirus infections were available, including 12 in vitro studies (reporting an inconstant inhibition of viral replication), two preclinical studies (reporting contradictory results), and no clinical trials. Meanwhile, 253 therapeutic clinical trials featuring an HCQ arm were registered in 2020, intending to enrol 246,623 patients. CONCLUSIONS The number and size of (H)CQ clinical trials for COVID-19 launched in 2020 were not supported by the literature published before April 2020.
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Affiliation(s)
- N Vieux
- Pôle Pharmacie, Université Grenoble Alpes, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France
| | - Q Perrier
- Pôle Pharmacie, Université Grenoble Alpes, Centre Hospitalier Universitaire Grenoble Alpes, Laboratory of Fundamental and Applied Bioenergetic (LBFA), INSERM U1055, Grenoble, France
| | - P Bedouch
- Pôle Pharmacie, Université Grenoble Alpes, Centre Hospitalier Universitaire Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, CHU Grenoble Alpes, TIMC, 38000 Grenoble, France
| | - O Epaulard
- Infectious Disease Department, Université Grenoble Alpes, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France; Groupe de Recherche en Infectiologie Clinique, CIC-1406, INSERM-UGA-CHUGA, France.
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14
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Matusik E, Demanet J, Alves I, Tone A, Ettahar N, Lemtiri J, Potey C, Gautier S, Lambiotte F, Gaboriau L. Fosfomycin-induced agranulocytosis: a case report and review of the literature. BMC Infect Dis 2023; 23:685. [PMID: 37833638 PMCID: PMC10576332 DOI: 10.1186/s12879-023-08652-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Accepted: 09/26/2023] [Indexed: 10/15/2023] Open
Abstract
BACKGROUND The intravenous form of fosfomycin, a bactericide antibiotic used to treat multiresistant bacterial infections is little prescribed. The most common reported adverse effects are hypokaliemia and hypernatremia. We describe a case of agranulocytosis, a rarely described side effect that may be fatal. CASE PRESENTATION A 45 year-old woman was admitted to the intensive care unit for post-surgical meningitis following meningioma resection. Meropenem and vancomycin were first introduced. A DRESS-syndrom with meropenem was suspected. Neutropenia was diagnosed three days after the introduction of parenteral fosfomycin and agranulocytosis four days later. Eosinophilia was also observed. A bone marrow aspiration was performed showing a disappearance of the neutrophil granulocyte line and a significant eosinophilia. Meropenem was discontinued. Fosfomycin was maintained and filgrastim was added. As filgrastim had no effect, the relationship with fosfomycin was suspected, so it was then withheld. An increase of the neutrophil count was observed. Because of the complexity of the case, the unfavorable course of the illness and the urgent need for revision surgery, a rechallenge with fosfomycin was done followed by a decrease of the neutrophil count. CONCLUSION This is the third paper reporting agranulocytosis induced by fosfomycin, and the first detailed description of a case. Based on chronological and semiological criteria and bibliographic data, the event was qualified as probable with the Naranjo adverse drug probability scale. Literature data is scarce. The summary of product characteristics mentions that only a few cases of transient neutropenia and agranulocytosis have been reported. An analysis of the FDA Adverse Event Reporting System Database highlighted a higher than expected frequency of agranulocytosis in patients treated with fosfomycin. Parenteral fosfomycin is often used in patients receiving other medications, so that it is rarely the only suspect. In our case, the results of the bone marrow aspiration, the sudden drop of the neutrophil count with concomitant eosinophilia and the absence of improvement despite the dose decrease, point towards an immuno-allergic mechanism. However, the overlap between the suspected DRESS induced by meropenem and the agranulocytosis do not allow to conclude with certainty on the causality. Awareness should be raised about this side effect.
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Affiliation(s)
- Elodie Matusik
- Centre Hospitalier de Valenciennes, Valenciennes, France.
| | - Julien Demanet
- Centre Hospitalier de Valenciennes, Valenciennes, France
| | - Isabelle Alves
- Centre Hospitalier de Valenciennes, Valenciennes, France
| | - Alina Tone
- Centre Hospitalier de Valenciennes, Valenciennes, France
| | | | | | - Camille Potey
- Centre Hospitalier Régional et Universitaire de Lille, Lille, France
| | - Sophie Gautier
- Centre Hospitalier Régional et Universitaire de Lille, Lille, France
| | | | - Louise Gaboriau
- Centre Hospitalier Régional et Universitaire de Lille, Lille, France
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15
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Niort K, Dancourt J, Boedec E, Al Amir Dache Z, Lavieu G, Tareste D. Cholesterol and Ceramide Facilitate Membrane Fusion Mediated by the Fusion Peptide of the SARS-CoV-2 Spike Protein. ACS OMEGA 2023; 8:32729-32739. [PMID: 37720777 PMCID: PMC10500581 DOI: 10.1021/acsomega.3c03610] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Accepted: 07/17/2023] [Indexed: 09/19/2023]
Abstract
SARS-CoV-2 entry into host cells is mediated by the Spike (S) protein of the viral envelope. The S protein is composed of two subunits: S1 that induces binding to the host cell via its interaction with the ACE2 receptor of the cell surface and S2 that triggers fusion between viral and cellular membranes. Fusion by S2 depends on its heptad repeat domains that bring membranes close together and its fusion peptide (FP) that interacts with and perturbs the membrane structure to trigger fusion. Recent studies have suggested that cholesterol and ceramide lipids from the cell surface may facilitate SARS-CoV-2 entry into host cells, but their exact mode of action remains unknown. We have used a combination of in vitro liposome-liposome and in situ cell-cell fusion assays to study the lipid determinants of S-mediated membrane fusion. Our findings reveal that both cholesterol and ceramide lipids facilitate fusion, suggesting that targeting these lipids could be effective against SARS-CoV-2. As a proof of concept, we examined the effect of chlorpromazine (CPZ), an antipsychotic drug known to perturb membrane structure. Our results show that CPZ effectively inhibits S-mediated membrane fusion, thereby potentially impeding SARS-CoV-2 entry into the host cell.
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Affiliation(s)
- Kristina Niort
- Université
Paris Cité, Inserm UMR-S 1266, Institute of Psychiatry and
Neuroscience of Paris (IPNP), Paris 75014, France
| | - Julia Dancourt
- Université
Paris Cité, Inserm U 1316, CNRS UMR 7057, Laboratoire Matières
et Systèmes Complexes (MSC), Paris 75006, France
| | - Erwan Boedec
- Université
Paris Cité, Inserm UMR-S 1266, Institute of Psychiatry and
Neuroscience of Paris (IPNP), Paris 75014, France
| | - Zahra Al Amir Dache
- Université
Paris Cité, Inserm U 1316, CNRS UMR 7057, Laboratoire Matières
et Systèmes Complexes (MSC), Paris 75006, France
| | - Grégory Lavieu
- Université
Paris Cité, Inserm U 1316, CNRS UMR 7057, Laboratoire Matières
et Systèmes Complexes (MSC), Paris 75006, France
| | - David Tareste
- Université
Paris Cité, Inserm UMR-S 1266, Institute of Psychiatry and
Neuroscience of Paris (IPNP), Paris 75014, France
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16
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Mishra S, Mishra AK, Sharma R. Structural dynamics of chlorpromazine (CPZ) drug with dipalmitoylphosphatidylcholine (DPPC) lipid: a potential drug for SARS-CoV-2. J Biomol Struct Dyn 2023; 41:7595-7602. [PMID: 36124814 DOI: 10.1080/07391102.2022.2123393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Accepted: 09/04/2022] [Indexed: 10/14/2022]
Abstract
There is an urgent requirement for drug discovery and more importantly drug repositioning due to infectious new Severe Acute Respiratory Syndrome coronavirus 2. As per the recent report published in the journal L'Encéphale in May 2020, there is a planned ReCoVery Study examining the repurposing the chlorpromazine for the treatment of COVID-19. Here, we apply a combined Raman microspectroscopy and DFT-MD approach to investigate the structural dynamics of the Chlorpromazine (CPZ) drug with dipalmitoylphosphatidylcholine (DPPC) lipid bilayer, identifying the specific position of the drug in the DPPC lipid bilayer. The intensity ratios of the Raman peaks I2935/I2880, I1097/I1064 and I1097/I1129 are representative of the interaction of drugs with lipid alkyl chains and furnish conformation of lipid alkyl chains. Raman imaging microscopy for the study of the distribution of CPZ inside the lipid vesicles is reported. We also investigated the influence of order and disorder ratio in the CPZ on the DPPC liposomes prepared on phase transition temperature. HIGHLIGHTSDrug-membrane interactions using micromolar concentrations of both lipid and drugs.Neuroleptic drug and DPPC vesicles composed of DPPC/drug mixtures reveal qualitative differences between the Raman spectraThe temperature-controlled Raman microspectroscopic study has demonstrated that below phase-transition temperature, the fatty acid chains of the phospholipids are stiff and packed in a highly ordered array.DFT and MD simulations to understand molecular interactions, structural dynamics, and Raman spectra.Above phase-transition temperature, the chains are disordered and possess more motional freedom. Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Soni Mishra
- Department of Physics, Graphic Era Hill University, Dehradun, India
| | - Abhishek Kumar Mishra
- Department of Physics, School of Engineering, University of Petroleum and Energy Studies, Dehradun, Uttrakhand, India
| | - Ramesh Sharma
- Department of Applied Science, Feroze Gandhi Institute of Engineering and Technology, Raebareli, Uttarpradesh, India
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17
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Abou Baker DH, Hassan EM, El Gengaihi S. An overview on medicinal plants used for combating coronavirus: Current potentials and challenges. JOURNAL OF AGRICULTURE AND FOOD RESEARCH 2023; 13:100632. [PMID: 37251276 PMCID: PMC10198795 DOI: 10.1016/j.jafr.2023.100632] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 05/01/2023] [Accepted: 05/09/2023] [Indexed: 05/31/2023]
Abstract
Worldwide, Severe acute respiratory syndrome Coronavirus (SARS-CoV-2) pandemic crisis, causing many morbidities, mortality, and devastating impact on economies, so the current outbreak of the CoV-2 is a major concern for global health. The infection spread quickly and caused chaos in many countries around the world. The slow discovery of CoV-2 and the limited treatment options are among the main challenges. Therefore, the development of a drug that is safe and effective against CoV-2 is urgently needed. The present overview briefly summarizes CoV-2 drug targets ex: RNA-dependent RNA polymerase (RdRp), papain-like protease (PLpro), 3-chymotrypsin-like protease (3CLpro), transmembrane serine protease enzymes (TMPRSS2), angiotensin-converting enzyme 2 (ACE2), structural protein (N, S, E, and M), and virulence factors (NSP1, ORF7a, and NSP3c) for which drug design perspective can be considered. In addition, summarize all anti-COVID-19 medicinal plants and phytocompounds and their mechanisms of action to be used as a guide for further studies.
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Affiliation(s)
- Doha H Abou Baker
- Medicinal and Aromatic Plants Dept., Pharmaceutical and Drug Industries Institute, National Research Centre, Cairo, Egypt
| | - Emad M Hassan
- Medicinal and Aromatic Plants Dept., Pharmaceutical and Drug Industries Institute, National Research Centre, Cairo, Egypt
| | - Souad El Gengaihi
- Medicinal and Aromatic Plants Dept., Pharmaceutical and Drug Industries Institute, National Research Centre, Cairo, Egypt
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18
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Bostanghadiri N, Ziaeefar P, Mofrad MG, Yousefzadeh P, Hashemi A, Darban-Sarokhalil D. COVID-19: An Overview of SARS-CoV-2 Variants-The Current Vaccines and Drug Development. BIOMED RESEARCH INTERNATIONAL 2023; 2023:1879554. [PMID: 37674935 PMCID: PMC10480030 DOI: 10.1155/2023/1879554] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Revised: 07/07/2023] [Accepted: 08/04/2023] [Indexed: 09/08/2023]
Abstract
The world is presently in crisis facing an outbreak of a health-threatening microorganism known as COVID-19, responsible for causing uncommon viral pneumonia in humans. The virus was first reported in Wuhan, China, in early December 2019, and it quickly became a global concern due to the pandemic. Challenges in this regard have been compounded by the emergence of several variants such as B.1.1.7, B.1.351, P1, and B.1.617, which show an increase in transmission power and resistance to therapies and vaccines. Ongoing researches are focused on developing and manufacturing standard treatment strategies and effective vaccines to control the pandemic. Despite developing several vaccines such as Pfizer/BioNTech and Moderna approved by the U.S. Food and Drug Administration (FDA) and other vaccines in phase 4 clinical trials, preventive measures are mandatory to control the COVID-19 pandemic. In this review, based on the latest findings, we will discuss different types of drugs as therapeutic options and confirmed or developing vaccine candidates against SARS-CoV-2. We also discuss in detail the challenges posed by the variants and their effect on therapeutic and preventive interventions.
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Affiliation(s)
- Narjess Bostanghadiri
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Pardis Ziaeefar
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Morvarid Golrokh Mofrad
- Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran
| | - Parsa Yousefzadeh
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Hashemi
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Davood Darban-Sarokhalil
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
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19
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Anesi GL, Degnan K, Dutcher L, Saw S, Maguire C, Binkley A, Patel S, Athans V, Barton TD, Binkley S, Candeloro CL, Herman DJ, Kasbekar N, Kennedy L, Millstein JH, Meyer NJ, Talati NJ, Patel H, Pegues DA, Sayre PJ, Tebas P, Terico AT, Murphy KM, O’Donnell JA, White M, Hamilton KW. The Penn Medicine COVID-19 Therapeutics Committee-Reflections on a Model for Rapid Evidence Review and Dynamic Practice Recommendations During a Public Health Emergency. Open Forum Infect Dis 2023; 10:ofad428. [PMID: 37663091 PMCID: PMC10468749 DOI: 10.1093/ofid/ofad428] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Accepted: 08/08/2023] [Indexed: 09/05/2023] Open
Abstract
The Penn Medicine COVID-19 Therapeutics Committee-an interspecialty, clinician-pharmacist, and specialist-front line primary care collaboration-has served as a forum for rapid evidence review and the production of dynamic practice recommendations during the 3-year coronavirus disease 2019 public health emergency. We describe the process by which the committee went about its work and how it navigated specific challenging scenarios. Our target audiences are clinicians, hospital leaders, public health officials, and researchers invested in preparedness for inevitable future threats. Our objectives are to discuss the logistics and challenges of forming an effective committee, undertaking a rapid evidence review process, aligning evidence-based guidelines with operational realities, and iteratively revising recommendations in response to changing pandemic data. We specifically discuss the arc of evidence for corticosteroids; the noble beginnings and dangerous misinformation end of hydroxychloroquine and ivermectin; monoclonal antibodies and emerging viral variants; and patient screening and safety processes for tocilizumab, baricitinib, and nirmatrelvir-ritonavir.
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Affiliation(s)
- George L Anesi
- Division of Pulmonary, Allergy, and Critical Care, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Kathleen Degnan
- Division of Infectious Diseases, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Lauren Dutcher
- Division of Infectious Diseases, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Stephen Saw
- Department of Pharmacy, Hospital of the University of Pennsylvania, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA
| | - Christina Maguire
- Department of Pharmacy, Penn Presbyterian Medical Center, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA
| | - Amanda Binkley
- Department of Pharmacy, Penn Presbyterian Medical Center, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA
| | - Sonal Patel
- Department of Pharmacy, Hospital of the University of Pennsylvania, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA
| | - Vasilios Athans
- Department of Pharmacy, Hospital of the University of Pennsylvania, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA
| | - Todd D Barton
- Division of Infectious Diseases, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Shawn Binkley
- Department of Pharmacy, Hospital of the University of Pennsylvania, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA
| | - Christina L Candeloro
- Department of Pharmacy, Hospital of the University of Pennsylvania, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA
| | - David J Herman
- Division of Infectious Diseases, Penn Medicine Princeton Medical Center, University of Pennsylvania Health System, Princeton, New Jersey, USA
| | - Nishaminy Kasbekar
- Department of Pharmacy, Penn Presbyterian Medical Center, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA
| | - Leigh Kennedy
- Division of Infectious Diseases, Pennsylvania Hospital, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA
| | - Jeffrey H Millstein
- Regional Physician Practices of Penn Medicine, Woodbury Heights, New Jersey, USA
| | - Nuala J Meyer
- Division of Pulmonary, Allergy, and Critical Care, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Naasha J Talati
- Division of Infectious Diseases, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Hinal Patel
- Department of Pharmacy, Penn Medicine Princeton Medical Center, University of Pennsylvania Health System, Princeton, New Jersey, USA
| | - David A Pegues
- Division of Infectious Diseases, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Patrick J Sayre
- Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Pablo Tebas
- Division of Infectious Diseases, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Adrienne T Terico
- Department of Pharmacy, Pennsylvania Hospital, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA
| | - Kathleen M Murphy
- Division of Infectious Diseases, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Judith A O’Donnell
- Division of Infectious Diseases, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Melissa White
- Department of Pharmacy, Penn Medicine Lancaster General Health, University of Pennsylvania Health System, Lancaster, Pennsylvania, USA
| | - Keith W Hamilton
- Division of Infectious Diseases, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
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20
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Steinbronn C, Chhonker YS, Stewart J, Leingang H, Heller KB, Krows ML, Paasche‐Orlow M, Bershteyn A, Stankiewicz Karita HC, Agrawal V, Laufer M, Landovitz R, Wener M, Murry DJ, Johnston C, Barnabas RV, Arnold SLM. A linked physiologically based pharmacokinetic model for hydroxychloroquine and metabolite desethylhydroxychloroquine in SARS-CoV-2(-)/(+) populations. Clin Transl Sci 2023; 16:1243-1257. [PMID: 37118968 PMCID: PMC10339702 DOI: 10.1111/cts.13527] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 03/13/2023] [Accepted: 03/29/2023] [Indexed: 04/30/2023] Open
Abstract
Hydroxychloroquine (HCQ) is Food and Drug Administration (FDA)-approved for malaria, systemic and chronic discoid lupus erythematosus, and rheumatoid arthritis. Because HCQ has a proposed multimodal mechanism of action and a well-established safety profile, it is often investigated as a repurposed therapeutic for a range of indications. There is a large degree of uncertainty in HCQ pharmacokinetic (PK) parameters which complicates dose selection when investigating its use in new disease states. Complications with HCQ dose selection emerged as multiple clinical trials investigated HCQ as a potential therapeutic in the early stages of the COVID-19 pandemic. In addition to uncertainty in baseline HCQ PK parameters, it was not clear if disease-related consequences of SARS-CoV-2 infection/COVID-19 would be expected to impact the PK of HCQ and its primary metabolite desethylhydroxychloroquine (DHCQ). To address the question whether SARS-CoV-2 infection/COVID-19 impacted HCQ and DHCQ PK, dried blood spot samples were collected from SARS-CoV-2(-)/(+) participants administered HCQ. When a previously published physiologically based pharmacokinetic (PBPK) model was used to fit the data, the variability in exposure of HCQ and DHCQ was not adequately captured and DHCQ concentrations were overestimated. Improvements to the previous PBPK model were made by incorporating the known range of blood to plasma concentration ratios (B/P) for each compound, adjusting HCQ and DHCQ distribution settings, and optimizing DHCQ clearance. The final PBPK model adequately captured the HCQ and DHCQ concentrations observed in SARS-CoV-2(-)/(+)participants, and incorporating COVID-19-associated changes in cytochrome P450 activity did not further improve model performance for the SARS-CoV-2(+) population.
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Affiliation(s)
- Claire Steinbronn
- Department of PharmaceuticsUniversity of WashingtonSeattleWashingtonUSA
| | - Yashpal S. Chhonker
- Department of Pharmacy Practice and ScienceUniversity of Nebraska Medical CenterOmahaNebraskaUSA
| | - Jenell Stewart
- Division of Infectious DiseasesHennepin Healthcare Research InstituteMinneapolisMinnesotaUSA
- Department of MedicineUniversity of MinnesotaMinneapolisMinnesotaUSA
| | - Hannah Leingang
- Department of MedicineUniversity of WashingtonSeattleWashingtonUSA
| | - Kate B. Heller
- Department of MedicineUniversity of WashingtonSeattleWashingtonUSA
| | - Meighan L. Krows
- Department of Global HealthUniversity of WashingtonSeattleWashingtonUSA
| | - Michael Paasche‐Orlow
- Department of MedicineTufts Medical CenterBostonMassachusettsUSA
- Division of Primary CareTufts Medical CenterBostonMassachusettsUSA
| | - Anna Bershteyn
- Department of Population HealthNew York University Grossman School of MedicineNew YorkNew YorkUSA
| | | | - Vaidehi Agrawal
- Center for Vaccine Development and Global HealthUniversity of Maryland BaltimoreBaltimoreMarylandUSA
| | - Miriam Laufer
- Center for Vaccine Development and Global HealthUniversity of Maryland BaltimoreBaltimoreMarylandUSA
| | - Raphael Landovitz
- UCLA Center for Clinical AIDS Research and EducationDavid Geffen School of Medicine at UCLALos AngelesCaliforniaUSA
| | - Mark Wener
- Department of MedicineUniversity of WashingtonSeattleWashingtonUSA
| | - Daryl J. Murry
- Department of Pharmacy Practice and ScienceUniversity of Nebraska Medical CenterOmahaNebraskaUSA
| | | | - Ruanne V. Barnabas
- Massachusetts General HospitalBostonMassachusettsUSA
- Harvard Medical SchoolBostonMassachusettsUSA
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21
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Smolic M, Dawood R, Salum G, Abd El Meguid M, Omran M, Smolic R. Therapeutic Interventions for COVID-19. POST COVID-19 - EFFECTS ON HUMAN HEALTH 2023. [DOI: 10.5772/intechopen.111543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/01/2023]
Abstract
SARS-CoV-2, a novel coronavirus, is currently represented a major public health concern. The high transmission rate of this virus increases the mortality rate worldwide. To date, significant efforts and restricted regulations were performed around the world to control this crisis effectively, but unfortunately, there is no specific and successful therapy for COVID-19. Many approaches have been repurposed for SARS-CoV-2 treatment such as antivirals and anti-inflammatories. Furthermore, antibody therapies are one of the main and important approaches of SARS-CoV-2 infection treatment. In recent trials, various immunotherapeutic interventions such as convalescent plasma therapy and monoclonal antibodies, as well as immunomodulatory agents are being proposed. However, the development of a vaccine that provides durable protective immunity will be the most effective therapy for controlling possible epidemics of this virus. The current review summarized all the proposed therapeutic approaches together with information on their safety and efficacy in treating COVID-19, as well as the vaccine candidates. The provided comprehensive information regarding the applied therapeutic strategies against COVID-19 might help the scientific community in any progress toward the treatment of COVID-19 infection.
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22
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Saxena D, Batra L, Verma SK. Broad-Spectrum Antivirals against Multiple Human and Animal Coronaviruses Infection. Pathogens 2023; 12:823. [PMID: 37375513 DOI: 10.3390/pathogens12060823] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 06/07/2023] [Indexed: 06/29/2023] Open
Abstract
Among the seven coronaviruses that infect humans, HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1 usually cause mild and common cold symptoms; however, infection with three coronaviruses, namely severe acute respiratory syndrome coronavirus [SARS-CoV], Middle East respiratory syndrome coronavirus [MERS-CoV], and the newly identified severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], often results in respiratory distress, cytokine storm and multiorgan failure [...].
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Affiliation(s)
- Divyasha Saxena
- Center for Predictive Medicine, University of Louisville, Louisville, KY 40202, USA
| | - Lalit Batra
- Center for Predictive Medicine, University of Louisville, Louisville, KY 40202, USA
| | - Shailendra Kumar Verma
- Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, San Diego, CA 92037, USA
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23
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Aranda J, Loureiro-Amigo J, Murgadella A, Vàzquez N, Feria L, Muñoz M, Padulles A, Abelenda G, Garcia-Vidal C, Tuset M, Albanell M, Boix-Palop L, Sanmartí-Martínez N, Gómez-Zorrilla S, Echeverria-Esnal D, Rodriguez-Alarcón A, Borjabad B, Coloma A, Carratalà J, Oriol I. Changing Trends in the Global Consumption of Treatments Used in Hospitalized Patients for COVID-19: A Time Series Multicentre Study. Antibiotics (Basel) 2023; 12:antibiotics12050809. [PMID: 37237712 DOI: 10.3390/antibiotics12050809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2023] [Revised: 04/12/2023] [Accepted: 04/19/2023] [Indexed: 05/28/2023] Open
Abstract
AIM To analyze trends in the prescription of COVID-19 treatments for hospitalized patients during the pandemic. METHODS Multicenter, ecological, time-series study of aggregate data for all adult patients with COVID-19 treated in five acute-care hospitals in Barcelona, Spain, between March 2020 and May 2021. Trends in the monthly prevalence of drugs used against COVID-19 were analyzed by the Mantel-Haenszel test. RESULTS The participating hospitals admitted 22,277 patients with COVID-19 during the study period, reporting an overall mortality of 10.8%. In the first months of the pandemic, lopinavir/ritonavir and hydroxychloroquine were the most frequently used antivirals, but these fell into disuse and were replaced by remdesivir in July 2020. By contrast, the trend in tocilizumab use varied, first peaking in April and May 2020, declining until January 2021, and showing a discrete upward trend thereafter. Regarding corticosteroid use, we observed a notable upward trend in the use of dexamethasone 6 mg per day from July 2020. Finally, there was a high prevalence of antibiotics use, especially azithromycin, in the first three months, but this decreased thereafter. CONCLUSIONS Treatment for patients hospitalized with COVID-19 evolved with the changing scientific evidence during the pandemic. Initially, multiple drugs were empirically used that subsequently could not demonstrate clinical benefit. In future pandemics, stakeholders should strive to promote the early implementation of adaptive randomized clinical trials.
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Affiliation(s)
- Judit Aranda
- Infectious Diseases Department, Complex Hospitalari Moisès Broggi, 08970 Sant Joan Despí, Spain
| | - Jose Loureiro-Amigo
- Infectious Diseases Department, Complex Hospitalari Moisès Broggi, 08970 Sant Joan Despí, Spain
| | - Anna Murgadella
- Pharmacy Department, Complex Hospitalari Moisès Broggi, 08970 Sant Joan Despí, Spain
| | - Núria Vàzquez
- Infectious Diseases Department, Complex Hospitalari Moisès Broggi, 08970 Sant Joan Despí, Spain
| | - Lucía Feria
- Infectious Diseases Department, Complex Hospitalari Moisès Broggi, 08970 Sant Joan Despí, Spain
| | - Miriam Muñoz
- Pharmacy Department, Hospital Universitari de Bellvitge, 08907 L'Hospitalet de Llobregat, Spain
| | - Ariadna Padulles
- Pharmacy Department, Hospital Universitari de Bellvitge, 08907 L'Hospitalet de Llobregat, Spain
- Bellvitge Biomedical Research Institute (IDIBELL), 08907 L'Hospitalet de Llobregat, Spain
- Center for Biomedical Research in Infectious Diseases Network (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Gabriela Abelenda
- Infectious Diseases Department, Hospital Universitari de Bellvitge, 08907 L'Hospitalet de Llobregat, Spain
| | - Carol Garcia-Vidal
- Center for Biomedical Research in Infectious Diseases Network (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Infectious Diseases Department, Hospital Clínic de Barcelona, 08036 Barcelona, Spain
| | - Montse Tuset
- Pharmacy Department, Hospital Clínic de Barcelona, 08036 Barcelona, Spain
| | - Marta Albanell
- Pharmacy Department, Hospital Clínic de Barcelona, 08036 Barcelona, Spain
| | - Lucía Boix-Palop
- Infectious Diseases Department, Hospital Mútua de Terrassa, 08221 Terrassa, Spain
| | | | - Sílvia Gómez-Zorrilla
- Infectious Diseases Department, Hospital del Mar, Infectious Pathology and Antimicrobials Research Group (IPAR), Institut Hospital del Mar d'Investigacions Mèdiques (IMIM) (Center Associated with the Universitat Pompeu Fabra), 08003 Barcelona, Spain
| | - Daniel Echeverria-Esnal
- Pharmacy Department, Hospital del Mar, Parc De Salut Mar, Infectious Pathology and Antimicrobials Research Group (IPAR), Institut Hospital del Mar d'Investigacions Mèdiques (IMIM) (Center Associated with the Universitat Pompeu Fabra), 08003 Barcelona, Spain
| | - Alicia Rodriguez-Alarcón
- Pharmacy Department, Hospital del Mar, Parc De Salut Mar, Infectious Pathology and Antimicrobials Research Group (IPAR), Institut Hospital del Mar d'Investigacions Mèdiques (IMIM) (Center Associated with the Universitat Pompeu Fabra), 08003 Barcelona, Spain
| | - Beatriz Borjabad
- Infectious Diseases Department, Complex Hospitalari Moisès Broggi, 08970 Sant Joan Despí, Spain
| | - Ana Coloma
- Infectious Diseases Department, Complex Hospitalari Moisès Broggi, 08970 Sant Joan Despí, Spain
| | - Jordi Carratalà
- Bellvitge Biomedical Research Institute (IDIBELL), 08907 L'Hospitalet de Llobregat, Spain
- Center for Biomedical Research in Infectious Diseases Network (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Infectious Diseases Department, Hospital Universitari de Bellvitge, 08907 L'Hospitalet de Llobregat, Spain
- Clinical Science Department, Faculty of Medicine, University of Barcelona, 08036 Barcelona, Spain
| | - Isabel Oriol
- Infectious Diseases Department, Complex Hospitalari Moisès Broggi, 08970 Sant Joan Despí, Spain
- Bellvitge Biomedical Research Institute (IDIBELL), 08907 L'Hospitalet de Llobregat, Spain
- Clinical Science Department, Faculty of Medicine, University of Barcelona, 08036 Barcelona, Spain
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24
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Sun Q, Li X, Kuang E. Subversion of autophagy machinery and organelle-specific autophagy by SARS-CoV-2 and coronaviruses. Autophagy 2023; 19:1055-1069. [PMID: 36005882 PMCID: PMC10012907 DOI: 10.1080/15548627.2022.2116677] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 08/18/2022] [Accepted: 08/19/2022] [Indexed: 12/09/2022] Open
Abstract
As a new emerging severe coronavirus, the knowledge on the SARS-CoV-2 and COVID-19 remains very limited, whereas many concepts can be learned from the homologous coronaviruses. Macroautophagy/autophagy is finely regulated by SARS-CoV-2 infection and plays important roles in SARS-CoV-2 infection and pathogenesis. This review will explore the subversion and mechanism of the autophagy-related machinery, vacuoles and organelle-specific autophagy during infection of SARS-CoV-2 and coronaviruses to provide meaningful insights into the autophagy-related therapeutic strategies for infectious diseases of SARS-CoV-2 and coronaviruses.
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Affiliation(s)
- Qinqin Sun
- Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Xiaojuan Li
- College of Clinic Medicine, Hubei University of Chinese Medicine, Wuhan, Hubei, China
| | - Ersheng Kuang
- Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China
- Ministry of Education, Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Guangzhou, Guangdong, China
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25
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Ang D, Kendall R, Atamian HS. Virtual and In Vitro Screening of Natural Products Identifies Indole and Benzene Derivatives as Inhibitors of SARS-CoV-2 Main Protease (M pro). BIOLOGY 2023; 12:biology12040519. [PMID: 37106720 PMCID: PMC10135783 DOI: 10.3390/biology12040519] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 03/25/2023] [Accepted: 03/26/2023] [Indexed: 04/29/2023]
Abstract
The rapid spread of the coronavirus disease 2019 (COVID-19) resulted in serious health, social, and economic consequences. While the development of effective vaccines substantially reduced the severity of symptoms and the associated deaths, we still urgently need effective drugs to further reduce the number of casualties associated with SARS-CoV-2 infections. Machine learning methods both improved and sped up all the different stages of the drug discovery processes by performing complex analyses with enormous datasets. Natural products (NPs) have been used for treating diseases and infections for thousands of years and represent a valuable resource for drug discovery when combined with the current computation advancements. Here, a dataset of 406,747 unique NPs was screened against the SARS-CoV-2 main protease (Mpro) crystal structure (6lu7) using a combination of ligand- and structural-based virtual screening. Based on 1) the predicted binding affinities of the NPs to the Mpro, 2) the types and number of interactions with the Mpro amino acids that are critical for its function, and 3) the desirable pharmacokinetic properties of the NPs, we identified the top 20 candidates that could potentially inhibit the Mpro protease function. A total of 7 of the 20 top candidates were subjected to in vitro protease inhibition assay and 4 of them (4/7; 57%), including two beta carbolines, one N-alkyl indole, and one Benzoic acid ester, had significant inhibitory activity against Mpro protease. These four NPs could be developed further for the treatment of COVID-19 symptoms.
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Affiliation(s)
- Dony Ang
- Computational and Data Sciences Program, Chapman University, Orange, CA 92866, USA
- Schmid College of Science and Technology, Chapman University, Orange, CA 92866, USA
| | - Riley Kendall
- Computational and Data Sciences Program, Chapman University, Orange, CA 92866, USA
- Schmid College of Science and Technology, Chapman University, Orange, CA 92866, USA
| | - Hagop S Atamian
- Schmid College of Science and Technology, Chapman University, Orange, CA 92866, USA
- Biological Sciences Program, Chapman University, Orange, CA 92866, USA
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26
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Öztürk Sözen E, Eryaşar E. QSPR Analysis of Some Drug Candidates Investigated for COVID-19 via New Topological Coindices. Polycycl Aromat Compd 2023. [DOI: 10.1080/10406638.2023.2191974] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/29/2023]
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27
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Kandeel M. An overview of the recent progress in Middle East Respiratory Syndrome Coronavirus (MERS-CoV) drug discovery. Expert Opin Drug Discov 2023; 18:385-400. [PMID: 36971501 DOI: 10.1080/17460441.2023.2192921] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/29/2023]
Abstract
INTRODUCTION The Middle East respiratory syndrome coronavirus (MERS-CoV) has remained a public health concern since it first emerged in 2012. Although many potential treatments for MERS-CoV have been developed and tested, none have had complete success in stopping the spread of this deadly disease. MERS-CoV replication comprises attachment, entry, fusion and replication steps. Targeting these events may lead to the creation of medications that effectively treat MERS-CoV infection. AREAS COVERED This review updates the research on the development of inhibitors of MERS-CoV. The main topics are MERS-CoV‒related proteins and host cell proteins that are involved in viral protein activation and infection. EXPERT OPINION Research on discovering drugs that can inhibit MERS-CoV started at a slow pace, and although efforts have steadily increased, clinical trials for new drugs specifically targeting MERS-CoV have not been extensive enough. The explosion in efforts to find new medications for the SARS-CoV-2 virus indirectly enhanced the volume of data on MERS-CoV inhibition by including MERS-CoV in drug assays. The appearance of COVID-19 completely transformed the data available on MERS-CoV inhibition. Despite the fact that new infected cases are constantly being diagnosed, there are currently no approved vaccines for or inhibitors of MERS-CoV.
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28
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Garaev TM, Grebennikova TV, Avdeeva VV, Lebedeva VV, Larichev VF. [Antiviral properties of synthetic histidine derivatives containing membranotropic volumetrical carbocycles in their molecule against SARS-CoV-2 virus in vitro]. Vopr Virusol 2023; 68:18-25. [PMID: 36961232 DOI: 10.36233/0507-4088-147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Indexed: 04/21/2023]
Abstract
INTRODUCTION Currently, low molecular-weight compounds are being developed as potential inhibitors of CoVs replication, targeting various stages of the replication cycle, such as major protease inhibitors and nucleoside analogs. Viroporins can be alternative protein targets. The aim of this study is to identify antiviral properties of histidine derivatives with cage substituents in relation to pandemic strain SARS-CoV-2 in vitro. MATERIALS AND METHODS Combination of histidine with aminoadamantane and boron cluster anion [B10H10]2 (compounds IIV) was carried out by classical peptide synthesis. Compound were identified by modern physicochemical methods. Antiviral properties were studied in vitro on a monolayer of Vero E6 cells infected with SARS-CoV-2 (alpha strain) with simultaneous administration of compounds and virus. RESULTS Derivatives of amino acid histidine with carbocycles and boron cluster were synthesized and their antiviral activity against SARS-CoV-2 was studied in vitro. Histidine derivatives with carbocycles and [B10H10]2 have the ability to suppress virus replication. The solubility of substances in aqueous media can be increased due to formation of hydrochloride or sodium salt. DISCUSSION 2HCl*H-His-Rim (I) showed some effect of suppressing replication of SARS-CoV-2 at a viral load of 100 doses and concentration 31.2 g/ml. This is explained by the weakly basic properties of compound I. CONCLUSION The presented synthetic compounds showed moderate antiviral activity against SARS-CoV-2. The obtained compounds can be used as model structures for creating new direct-acting drugs against modern strains of coronaviruses.
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Affiliation(s)
- T M Garaev
- National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya
| | - T V Grebennikova
- National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya
| | - V V Avdeeva
- Kurnakov Institute of General and Inorganic Chemistry of Russian Academy of Sciences
| | - V V Lebedeva
- National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya
| | - V F Larichev
- National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya
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29
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Venturas JP. HIV and COVID-19 Disease. Semin Respir Crit Care Med 2023; 44:35-49. [PMID: 36646084 DOI: 10.1055/s-0042-1758852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Despite effective antiretroviral therapy (ART), HIV infected individuals throughout the world remain at significant risk of respiratory infections and non-communicable disease. Severe disease from SARS-CoV-2 is associated with a hyperinflammatory phenotype which manifests in the lungs as pneumonia and in some cases can lead to acute respiratory failure. Progression to severe COVID-19 is associated with comorbid disease such as obesity, diabetes mellitus and cardiovascular disease, however data concerning the associated risks of HIV coinfection are still conflicting, with large population studies demonstrating poorer outcomes, whilst smaller, case-controlled studies showing better outcomes. Furthermore, underlying immunopathological processes within the lungs and elsewhere, including interactions with other opportunistic infections (OI), remain largely undefined. Nonetheless, new and repurposed anti-viral therapies and vaccines which have been developed are safe to use in this population, and anti-inflammatory agents are recommended with the caveat that the coexistence of opportunistic infections is considered and excluded. Finally, HIV infected patients remain reliant on good ART adherence practices to maintain HIV viral suppression, and some of these practices were disrupted during the COVID-19 pandemic, putting these patients at further risk for acute and long-term adverse outcomes.
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Affiliation(s)
- Jacqui P Venturas
- Department of Internal Medicine and Pulmonology, Charlotte Maxeke Johannesburg Academic Hospital and Universtity of the Witwatersrand, Johannesburg, South Africa
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30
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Khani S, Tafaroji J, Yaghoubi M, Emami Kazemabad MJ, Hejazi SA. Prevalence of COVID-19 outcomes in patients referred to opioid agonist treatment centers. Front Pharmacol 2023; 14:1105176. [PMID: 37033605 PMCID: PMC10076798 DOI: 10.3389/fphar.2023.1105176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Accepted: 03/15/2023] [Indexed: 04/11/2023] Open
Abstract
Background: Coronavirus disease (COVID-19) is a mild to severe infectious respiratory illness caused by the SARS-CoV-2 virus. Based on the numerous pieces of evidence regarding the role of opioids in immune function, viral replication, and virus-mediated pathology, we decided to assess the incidence and severity of COVID-19 outcomes in people undergoing opioid maintenance treatment. Methods: This is a prospective, descriptive, multi-center study that included 452 patients undergoing maintenance treatment in opioid agonist treatment (OAT) clinics in different cities of Iran. Demographic information, underlying disease, history of maintenance treatment, type of drug used, history of addiction, smoking, and the kind of substance abused, were recorded. A physician evaluated the COVID-19 symptoms, and the severity of the disease was defined based on the number of observed symptoms. Results: The results have not shown any significant difference in the severity of COVID-19 symptoms in different nationalities, gender, and treatment groups. Furthermore, the history of drug abuse, including time and type of abuse and smoking, has not indicated any significant association with the occurrence of symptoms. Only the severity of COVID-19 in the mentioned cities (first and second follow-up: p < 0.001) and individuals with a history of underlying disease (first follow-up: p = 0.020; second follow-up: p = 0.043) were significantly different. Conclusion: Our results have demonstrated that the severity of symptoms in people with the underlying disease was significantly higher than in others. But there is no association between sex, race, treatment groups, and abuse history with the severity of COVID-19 symptoms in methadone maintenance treatment (MMT) patients.
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Affiliation(s)
- Samira Khani
- Neuroscience Research Center, Qom University of Medical Sciences, Qom, Iran
| | - Javad Tafaroji
- Pediatric Medicine Research Center, Qom University of Medical Sciences, Qom, Iran
| | - Mehdi Yaghoubi
- Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran
| | | | - Seyed Amir Hejazi
- Neuroscience Research Center, Qom University of Medical Sciences, Qom, Iran
- *Correspondence: Seyed Amir Hejazi,
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31
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Kumar A, Sharma A, Tirpude NV, Thakur S, Kumar S. Combating the Progression of Novel Coronavirus SARS-CoV-2 Infectious Disease: Current State and Future Prospects in Molecular Diagnostics and Drug Discovery. Curr Mol Med 2023; 23:127-146. [PMID: 34344288 DOI: 10.2174/1566524021666210803154250] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Revised: 04/07/2021] [Accepted: 04/14/2021] [Indexed: 12/16/2022]
Abstract
A highly infectious and life-threatening virus was first reported in Wuhan, China, in late 2019, and it rapidly spread all over the world. This novel virus belongs to the coronavirus family and is associated with severe acute respiratory syndrome (SARS), causing respiratory disease known as COVID-19. In March 2020, WHO has declared the COVID-19 outbreak a global pandemic. Its morbidity and mortality rates are swiftly rising day by day, with the situation becoming more severe and fatal for the comorbid population. Many COVID-19 patients are asymptomatic, but they silently spread the infection. There is a need for proper screening of infected patients to prevent the epidemic transmission of disease and for early curative interventions to reduce the risk of developing severe complications from COVID-19. To date, the diagnostic assays are of two categories, molecular detection of viral genetic material by real-time RTpolymerase chain reaction and serological test, which relies on detecting antiviral antibodies. Unfortunately, there are no effective prophylactics and therapeutics available against COVID-19. However, a few drugs have shown promising antiviral activity against it, and these presently are being referred for clinical trials, albeit FDA has issued an Emergency Use Authorization (EUA) for the emergency use of a few drugs for SARSCoV- 2 infection. This review provides an insight into current progress, challenges and future prospects of laboratory detection methods of COVID-19, and highlights the clinical stage of the major evidence-based drugs/vaccines recommended against the novel SARS-CoV-2 pandemic virus.
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Affiliation(s)
- Arbind Kumar
- COVID-19 Testing Facility, CSIR-Institute of Himalayan Bioresource& Technology (IHBT), Palampur, India
| | - Aashish Sharma
- COVID-19 Testing Facility, CSIR-Institute of Himalayan Bioresource& Technology (IHBT), Palampur, India
| | - Narendra Vijay Tirpude
- COVID-19 Testing Facility, CSIR-Institute of Himalayan Bioresource& Technology (IHBT), Palampur, India
| | - Sharad Thakur
- COVID-19 Testing Facility, CSIR-Institute of Himalayan Bioresource& Technology (IHBT), Palampur, India
| | - Sanjay Kumar
- COVID-19 Testing Facility, CSIR-Institute of Himalayan Bioresource& Technology (IHBT), Palampur, India
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Jeong K, Chang J, Park SM, Kim J, Jeon S, Kim DH, Kim YE, Lee JC, Im S, Jo Y, Min JY, Lee H, Yeom M, Seok SH, On DI, Noh H, Yun JW, Park JW, Song D, Seong JK, Kim KC, Lee JY, Park HJ, Kim S, Nam TG, Lee W. Rapid discovery and classification of inhibitors of coronavirus infection by pseudovirus screen and amplified luminescence proximity homogeneous assay. Antiviral Res 2023; 209:105473. [PMID: 36435212 PMCID: PMC9682871 DOI: 10.1016/j.antiviral.2022.105473] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Revised: 11/16/2022] [Accepted: 11/18/2022] [Indexed: 11/24/2022]
Abstract
To identify potent antiviral compounds, we introduced a high-throughput screen platform that can rapidly classify hit compounds according to their target. In our platform, we performed a compound screen using a lentivirus-based pseudovirus presenting a spike protein of coronavirus, and we evaluated the hit compounds using an amplified luminescence proximity homogeneous assay (alpha) test with purified host receptor protein and the receptor binding domain of the viral spike. With our screen platform, we were able to identify both spike-specific compounds (class I) and broad-spectrum antiviral compounds (class II). Among the hit compounds, thiosemicarbazide was identified to be selective to the interaction between the viral spike and its host cell receptor, and we further optimized the binding potency of thiosemicarbazide through modification of the pyridine group. Among the class II compounds, we found raloxifene and amiodarone to be highly potent against human coronaviruses including Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), and SARS-CoV-2. In particular, using analogs of the benzothiophene moiety, which is also present in raloxifene, we have identified benzothiophene as a novel structural scaffold for broad-spectrum antivirals. This work highlights the strong utility of our screen platform using a pseudovirus assay and an alpha test for rapid identification of potential antiviral compounds and their mechanism of action, which can lead to the accelerated development of therapeutics against newly emerging viral infections.
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Affiliation(s)
- Kwiwan Jeong
- Bio-center, Gyeonggido Business and Science Accelerator, Suwon, South Korea,Corresponding author
| | - JuOae Chang
- Department of Pharmacy, School of Pharmacy, Sungkyunkwan University, Suwon, South Korea
| | - Sun-mi Park
- Bio-center, Gyeonggido Business and Science Accelerator, Suwon, South Korea
| | - Jinhee Kim
- Institut Pasteur Korea, Seongnam, South Korea
| | | | - Dong Hwan Kim
- Department of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, South Korea
| | - Young-Eui Kim
- Center for Emerging Virus Research, National Institute of Infectious Diseases, National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, South Korea
| | - Joo Chan Lee
- Department of Pharmacy, School of Pharmacy, Sungkyunkwan University, Suwon, South Korea
| | - Somyoung Im
- Department of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, South Korea
| | - Yejin Jo
- Department of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, South Korea
| | | | - Hanbyeul Lee
- Department of Veterinary Medicine Virology Laboratory, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul, South Korea
| | - Minjoo Yeom
- Department of Veterinary Medicine Virology Laboratory, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul, South Korea
| | - Sang-Hyuk Seok
- Division of Biomedical Convergence, College of Biomedical Science, Kangwon National University, ChunCheon, South Korea
| | - Da In On
- Laboratory of Developmental Biology and Genomics, Research Institute for Veterinary Science, BK21 Program for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, South Korea,Korea Mouse Phenotyping Center (KMPC), Seoul National University, Seoul, South Korea
| | - Hyuna Noh
- Korea Mouse Phenotyping Center (KMPC), Seoul National University, Seoul, South Korea
| | - Jun-Won Yun
- Laboratory of Veterinary Toxicology, College of Veterinary Medicine, Seoul National University, Seoul, South Korea
| | - Jun Won Park
- Division of Biomedical Convergence, College of Biomedical Science, Kangwon National University, ChunCheon, South Korea
| | - Daesub Song
- Department of Veterinary Medicine Virology Laboratory, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul, South Korea
| | - Je Kyung Seong
- Laboratory of Developmental Biology and Genomics, Research Institute for Veterinary Science, BK21 Program for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, South Korea,Korea Mouse Phenotyping Center (KMPC), Seoul National University, Seoul, South Korea,Interdisciplinary Program for Bioinformatics, Program for Cancer Biology and BIO-MAX/N-Bio Institute, Seoul National University, Seoul, South Korea
| | - Kyung-Chang Kim
- Center for Emerging Virus Research, National Institute of Infectious Diseases, National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, South Korea
| | - Joo-Yeon Lee
- Center for Emerging Virus Research, National Institute of Infectious Diseases, National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, South Korea
| | - Hyun-Ju Park
- Department of Pharmacy, School of Pharmacy, Sungkyunkwan University, Suwon, South Korea,Corresponding author
| | - Seungtaek Kim
- Institut Pasteur Korea, Seongnam, South Korea,Corresponding author
| | - Tae-gyu Nam
- Department of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, South Korea,Corresponding author
| | - Wonsik Lee
- Department of Pharmacy, School of Pharmacy, Sungkyunkwan University, Suwon, South Korea,Corresponding author
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Daoud I, Mesli F, Melkemi N, Ghalem S, Salah T. Discovery of potential SARS-CoV 3CL protease inhibitors from approved antiviral drugs using: virtual screening, molecular docking, pharmacophore mapping evaluation and dynamics simulation. J Biomol Struct Dyn 2022; 40:12574-12591. [PMID: 34541995 PMCID: PMC8459931 DOI: 10.1080/07391102.2021.1973563] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
The spread of corona-virus disease 2019 (COVID-19) has been faster than any other corona-viruses that have succeeded in crossing the animal-human barrier. This disease, caused by the severe acute respiratory syndrome corona-virus 2 (SARS-CoV-2/2019-nCoV) posing a serious threat to global public health and local economies. There are three responsible for this disease; SARS-CoV-2, SARS-CoV and MERS-CoV. Whereas our goal is to test the affinity for a new class of compounds obtained from a hybridization of Chloroquine, Amodiaquine and Mefloquine with three targets SARS-CoV-2, SARS-CoV and MERS-CoV, in order to find new compounds as new inhibitors against Covid-19. In this work, we first used: the molecular docking/dynamics methods and ADME properties to study interaction and affinity between eight new compounds against three targets involved in the Covid-19. The results of the docking simulations and dynamics revealed that inhibitor of the malaria (Ligand 87) has an affinity to interact with SARS-CoV-2, SARS-CoV and MERS-CoV targets and they can be good inhibitors for treatment of Covid-19. Moreover, they give best affinity compared to the Remdesivir and Chloroquine and other clinical tests. The Pharmacokinetics was justified by means of lipophilicity and high coefficient of skin permeability. The in silico evaluation of ADME and drug-likeness revealed that L87 has higher absorption in the intestines with good bioavailability. However, an additional in vitro and/or in vivo experimental study should make it possible to verify the theoretical results obtained in silico.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Ismail Daoud
- Department of Matter Sciences, University Mohamed Khider, Biskra, Algeria,Faculty of Science, Laboratory of Natural and Bio-Actives Substances, Tlemcen University, Tlemcen, Algeria,Ismail Daoud Faculty of Science, Laboratory of Natural and Bio-Actives Substances, Tlemcen University, Tlemcen, Algeria
| | - Fouzia Mesli
- Faculty of Science, Laboratory of Natural and Bio-Actives Substances, Tlemcen University, Tlemcen, Algeria,CONTACT Fouzia Mesli ;
| | - Nadjib Melkemi
- Group of Computational and Pharmaceutical Chemistry LMCE Laboratory, University of Biskra, Algeria
| | - Said Ghalem
- Faculty of Science, Laboratory of Natural and Bio-Actives Substances, Tlemcen University, Tlemcen, Algeria
| | - Toufik Salah
- Group of Computational and Pharmaceutical Chemistry LMCE Laboratory, University of Biskra, Algeria
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Fayyazi N, Mostashari-Rad T, Ghasemi JB, Ardakani MM, Kobarfard F. Molecular dynamics simulation, 3D-pharmacophore and scaffold hopping analysis in the design of multi-target drugs to inhibit potential targets of COVID-19. J Biomol Struct Dyn 2022; 40:11787-11808. [PMID: 34405765 DOI: 10.1080/07391102.2021.1965914] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
SARS-CoV-2 has posed serious threat to the health and has inflicted huge costs in the world. Discovering potent compounds is a critical step to inhibit coronavirus. 3CLpro and RdRp are the most conserved targets associated with COVID-19. In this study, three-dimensional pharmacophore modeling, scaffold hopping, molecular docking, structure-based virtual screening, QSAR-based ADMET predictions and molecular dynamics analysis were used to identify inhibitors for these targets. Binding free energies estimated by molecular docking for each ligand in different binding sites of RdRp were used to predict the active site. Previously reported active 3CLpro and RdRp inhibitors were used to build a pharmacophore model to develop different scaffolds. Structure-based simulations and pharmacophore modeling based on Hip Hop algorithm converged in a state that suggest hydrogen bond acceptor and donor features have a critical role in the two binding sites. Further validations indicated that the best pharmacophore model has fairly good correlation values compared with approved inhibitors. Structure-based simulation results approved that GLu166 and Gln189 in 3CLpro and Lys551 and Glu811 in RdRp, are critical residues for dual activities. Ten compounds were extracted from pharmacophore-based virtual screening in six databases. The results, gained by repurposing approach, suggest the effectiveness of these ten compounds with different scaffolds as possible inhibitors of the two targets. Some quinoline-based hybrid derivatives also were designed. QSAR descriptors plot predicted that the scaffolds have had accepted pharmacokinetic profiles. Multiple molecular dynamics simulations in 100 ns and MM/PBSA studies of some reference inhibitors and the novel compounds in complex with both targets demonstrated stable complexes and confirmed the interaction modes. Based on different computational methods, COVID-19 multi-target inhibitors are proposed. Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Neda Fayyazi
- Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan, Iran.,Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Tahereh Mostashari-Rad
- Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan, Iran.,Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Jahan B Ghasemi
- College of Sciences, Faculty of Chemistry, University of Tehran, Tehran, Iran
| | - Mehran Mirabzadeh Ardakani
- Department of Traditional Pharmacy, Faculty of Pharmacy, Tehran University of Medical Science, Tehran, Iran
| | - Farzad Kobarfard
- Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.,Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Feng S, Zhang Y, Gao F, Li M, Zhu L, Wen H, Xi Y, Xiang X. Inhibitory Effects of Antipsychotic Chlorpromazine on the Survival, Reproduction and Population Growth Other Than Neurotransmitters of Zooplankton in Light of Global Warming. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:16167. [PMID: 36498239 PMCID: PMC9736287 DOI: 10.3390/ijerph192316167] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 11/17/2022] [Accepted: 11/30/2022] [Indexed: 06/17/2023]
Abstract
Global warming and environmental pollution have created a unique combination of abiotic and biotic stresses to zooplankton. However, little information is available on the effects of antipsychotic drugs commonly used to treat psychosis, such as chlorpromazine (CPZ), on non-target aquatic organisms in light of global warming. This study investigated how dopamine concentrations (DAC), acute toxicity and chronic toxicity of Brachionus calyciflorus changed in response to CPZ and gradually increasing temperatures. The results showed that the concentration range of rotifer DAC was 1.06~2.51 ng/g. At 18, 25 and 32 °C, the 24 h LC50 was 1.795, 1.242 and 0.833 mg/L, respectively. Compared to the control, exposure to CPZ significantly decreased life expectancy at hatching, the net reproduction rate, generation time, population growth rate and dopamine concentration of B. calyciflorus in all three temperatures (p < 0.05). The toxicity of CPZ to rotifers was increased by high temperature. These findings indicated that CPZ is highly toxic to rotifers, displaying high ecological risks to aquatic ecosystems.
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Affiliation(s)
- Sen Feng
- School of Ecology and Environment, Anhui Normal University, Wuhu 241002, China
| | - Yongzhi Zhang
- School of Ecology and Environment, Anhui Normal University, Wuhu 241002, China
| | - Fan Gao
- School of Ecology and Environment, Anhui Normal University, Wuhu 241002, China
| | - Meng Li
- School of Ecology and Environment, Anhui Normal University, Wuhu 241002, China
| | - Lingyun Zhu
- School of Ecology and Environment, Anhui Normal University, Wuhu 241002, China
| | - Hao Wen
- School of Ecology and Environment, Anhui Normal University, Wuhu 241002, China
| | - Yilong Xi
- School of Ecology and Environment, Anhui Normal University, Wuhu 241002, China
- Collaborative Innovation Center of Recovery and Reconstruction of Degraded Ecosystem in Wanjiang Basin Co-Founded by Anhui Province and Ministry of Education, Wuhu 241002, China
| | - Xianling Xiang
- School of Ecology and Environment, Anhui Normal University, Wuhu 241002, China
- Collaborative Innovation Center of Recovery and Reconstruction of Degraded Ecosystem in Wanjiang Basin Co-Founded by Anhui Province and Ministry of Education, Wuhu 241002, China
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36
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Balogun TA, Chukwudozie OS, Ogbodo UC, Junaid IO, Sunday OA, Ige OM, Aborode AT, Akintayo AD, Oluwarotimi EA, Oluwafemi IO, Saibu OA, Chuckwuemaka P, Omoboyowa DA, Alausa AO, Atasie NH, Ilesanmi A, Dairo G, Tiamiyu ZA, Batiha GE, Alkhuriji AF, Al-Megrin WAI, De Waard M, Sabatier JM. Discovery of putative inhibitors against main drivers of SARS-CoV-2 infection: Insight from quantum mechanical evaluation and molecular modeling. Front Chem 2022; 10:964446. [PMID: 36304744 PMCID: PMC9593047 DOI: 10.3389/fchem.2022.964446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Accepted: 08/10/2022] [Indexed: 11/13/2022] Open
Abstract
SARS-CoV-2 triggered a worldwide medical crisis, affecting the world’s social, emotional, physical, and economic equilibrium. However, treatment choices and targets for finding a solution to COVID-19’s threat are becoming limited. A viable approach to combating the threat of COVID-19 is by unraveling newer pharmacological and therapeutic targets pertinent in the viral survival and adaptive mechanisms within the host biological milieu which in turn provides the opportunity to discover promising inhibitors against COVID-19. Therefore, using high-throughput virtual screening, manually curated compounds library from some medicinal plants were screened against four main drivers of SARS-CoV-2 (spike glycoprotein, PLpro, 3CLpro, and RdRp). In addition, molecular docking, Prime MM/GBSA (molecular mechanics/generalized Born surface area) analysis, molecular dynamics (MD) simulation, and drug-likeness screening were performed to identify potential phytodrugs candidates for COVID-19 treatment. In support of these approaches, we used a series of computational modeling approaches to develop therapeutic agents against COVID-19. Out of the screened compounds against the selected SARS-CoV-2 therapeutic targets, only compounds with no violations of Lipinski’s rule of five and high binding affinity were considered as potential anti-COVID-19 drugs. However, lonchocarpol A, diplacol, and broussonol E (lead compounds) were recorded as the best compounds that satisfied this requirement, and they demonstrated their highest binding affinity against 3CLpro. Therefore, the 3CLpro target and the three lead compounds were selected for further analysis. Through protein–ligand mapping and interaction profiling, the three lead compounds formed essential interactions such as hydrogen bonds and hydrophobic interactions with amino acid residues at the binding pocket of 3CLpro. The key amino acid residues at the 3CLpro active site participating in the hydrophobic and polar inter/intra molecular interaction were TYR54, PRO52, CYS44, MET49, MET165, CYS145, HIS41, THR26, THR25, GLN189, and THR190. The compounds demonstrated stable protein–ligand complexes in the active site of the target (3CLpro) over a 100 ns simulation period with stable protein–ligand trajectories. Drug-likeness screening shows that the compounds are druggable molecules, and the toxicity descriptors established that the compounds demonstrated a good biosafety profile. Furthermore, the compounds were chemically reactive with promising molecular electron potential properties. Collectively, we propose that the discovered lead compounds may open the way for establishing phytodrugs to manage COVID-19 pandemics and new chemical libraries to prevent COVID-19 entry into the host based on the findings of this computational investigation.
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Affiliation(s)
- Toheeb A. Balogun
- Department of Biochemistry, Adekunle Ajasin University, Akungba-Akoko, Nigeria
- *Correspondence: Toheeb A. Balogun, ; Gaber E. Batiha,
| | - Onyeka S. Chukwudozie
- Department of Biological Sciences, University of California, San Diego, San Diego, CA, United States
| | | | - Idris O. Junaid
- Department of Chemistry and Chemical Biology, Stevens Institute of Technology, Hoboken, NJ, United States
| | - Olugbodi A. Sunday
- Department of Environmental Toxicology, Universitat Duisburg-Essen, Essen, Germany
| | - Oluwasegun M. Ige
- Department of Marine Biological Resources, Ghent University, Ghent, Belgium
| | - Abdullahi T. Aborode
- Department of Chemistry, Mississippi State University, Starkville, MS, United States
| | - Abiola D. Akintayo
- Department of Chemistry, University of Texas at Dallas, Richardson, TX, United States
| | - Emmanuel A. Oluwarotimi
- Department of Chemistry, Missouri University of Science and Technology, Rolla, MO, United States
| | - Isaac O. Oluwafemi
- Department of Chemistry, Adekunle Ajasin University, Akungba-Akoko, Nigeria
| | - Oluwatosin A. Saibu
- Department of Environmental Toxicology, Universitat Duisburg-Essen, Essen, Germany
| | - Prosper Chuckwuemaka
- Department of Biotechnology, Federal University of Technology Akure, Akure, Nigeria
| | | | | | - Nkechi H. Atasie
- Clinical Pharmacy Department, Nigeria Correctional Service, Enugu Custodial Centre, Enugu, Nigeria
| | - Ayooluwa Ilesanmi
- Department of Chemistry, Mississipi University for Women Columbus, Columbus, United States
| | - Gbenga Dairo
- Department of Biological Sciences, Western Illinois University, Macomb, IL, United States
| | - Zainab A. Tiamiyu
- Department of Biochemistry and Molecular Biology, Federal University Dutsin-ma, Dutsin-Ma, Nigeria
| | - Gaber E. Batiha
- Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, Egypt
- *Correspondence: Toheeb A. Balogun, ; Gaber E. Batiha,
| | - Afrah Fahad Alkhuriji
- Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Wafa Abdullah I. Al-Megrin
- Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Michel De Waard
- Smartox Biotechnology, Saint-Egréve, France
- L‘institut du Thorax, INSERM, CNRS, Université de Nantes, Nantes, France
- LabEx Ion Channels, Science and Therapeutics, Université de Nice Sophia-Antipolis, Valbonne, France
| | - Jean-Marc Sabatier
- Institut de Neurophysiopathologie (INP), Faculté des Sciences Médicales et Paramédicales, Aix-Marseille Université, CNRS UMR 7051, Marseille, France
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Trivedi P, Abbas A, Lehmann C, Rupasinghe HPV. Antiviral and Anti-Inflammatory Plant-Derived Bioactive Compounds and Their Potential Use in the Treatment of COVID-19-Related Pathologies. J Xenobiot 2022; 12:289-306. [PMID: 36278757 PMCID: PMC9589987 DOI: 10.3390/jox12040020] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 09/15/2022] [Accepted: 09/15/2022] [Indexed: 01/24/2023] Open
Abstract
The highly contagious coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been declared a global pandemic and public health emergency as it has taken the lives of over 5.7 million in more than 180 different countries. This disease is characterized by respiratory tract symptoms, such as dry cough and shortness of breath, as well as other symptoms, including fever, chills, and fatigue. COVID-19 is also characterized by the excessive release of cytokines causing inflammatory injury to the lungs and other organs. It is advised to undergo precautionary measures, such as vaccination, social distancing, use of masks, hygiene, and a healthy diet. This review is aimed at summarizing the pathophysiology of COVID-19 and potential biologically active compounds (bioactive) found in plants and plant food. We conclude that many plant food bioactive compounds exhibit antiviral and anti-inflammatory properties and support in attenuating organ damage due to reduced cytokine release and improving the recovery process from COVID-19 infection.
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Affiliation(s)
- Purvi Trivedi
- Department of Anesthesia, Pain Management and Perioperative Medicine, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 3E2, Canada
| | - Amna Abbas
- Department of Plant, Food, and Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS B2N 5E3, Canada
- Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4M1, Canada
| | - Christian Lehmann
- Department of Anesthesia, Pain Management and Perioperative Medicine, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 3E2, Canada
| | - H. P. Vasantha Rupasinghe
- Department of Plant, Food, and Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS B2N 5E3, Canada
- Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 3E2, Canada
- Correspondence:
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Copertino DC, Casado Lima BC, Duarte RRR, Powell TR, Ormsby CE, Wilkin T, Gulick RM, de Mulder Rougvie M, Nixon DF. Antiretroviral drug activity and potential for pre-exposure prophylaxis against COVID-19 and HIV infection. J Biomol Struct Dyn 2022; 40:7367-7380. [PMID: 33734021 PMCID: PMC8448789 DOI: 10.1080/07391102.2021.1901144] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Accepted: 02/24/2021] [Indexed: 12/18/2022]
Abstract
COVID-19 is the disease caused by SARS-CoV-2 which has led to 2,643,000 deaths worldwide, a number which is rapidly increasing. Urgent studies to identify new antiviral drugs, repurpose existing drugs, or identify drugs that can target the overactive immune response are ongoing. Antiretroviral drugs (ARVs) have been tested in past human coronavirus infections, and also against SARS-CoV-2, but a trial of lopinavir and ritonavir failed to show any clinical benefit in COVID-19. However, there is limited data as to the course of COVID-19 in people living with HIV, with some studies showing a decreased mortality for those taking certain ARV regimens. We hypothesized that ARVs other than lopinavir and ritonavir might be responsible for some protection against the progression of COVID-19. Here, we used chemoinformatic analyses to predict which ARVs would bind and potentially inhibit the SARS-CoV-2 main protease (Mpro) or RNA-dependent-RNA-polymerase (RdRp) enzymes in silico. The drugs predicted to bind the SARS-CoV-2 Mpro included the protease inhibitors atazanavir and indinavir. The ARVs predicted to bind the catalytic site of the RdRp included Nucleoside Reverse Transcriptase Inhibitors, abacavir, emtricitabine, zidovudine, and tenofovir. Existing or new combinations of antiretroviral drugs could potentially prevent or ameliorate the course of COVID-19 if shown to inhibit SARS-CoV-2 in vitro and in clinical trials. Further studies are needed to establish the activity of ARVs for treatment or prevention of SARS-CoV-2 infection .Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Dennis C. Copertino
- Division of Infectious Diseases, Weill Cornell Medicine, Cornell University, New York, NY, USA
| | - Bruno C. Casado Lima
- Division of Infectious Diseases, Weill Cornell Medicine, Cornell University, New York, NY, USA
| | - Rodrigo R. R. Duarte
- Division of Infectious Diseases, Weill Cornell Medicine, Cornell University, New York, NY, USA
| | - Timothy R. Powell
- Division of Infectious Diseases, Weill Cornell Medicine, Cornell University, New York, NY, USA
| | - Christopher E. Ormsby
- Center for Research in Infectious Diseases (CIENI), National Institute of Respiratory Diseases (INER), Mexico City, Mexico
| | - Timothy Wilkin
- Division of Infectious Diseases, Weill Cornell Medicine, Cornell University, New York, NY, USA
| | - Roy M. Gulick
- Division of Infectious Diseases, Weill Cornell Medicine, Cornell University, New York, NY, USA
| | | | - Douglas F. Nixon
- Division of Infectious Diseases, Weill Cornell Medicine, Cornell University, New York, NY, USA
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39
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Singh M, Jayant K, Singh D, Bhutani S, Poddar NK, Chaudhary AA, Khan SUD, Adnan M, Siddiqui AJ, Hassan MI, Khan FI, Lai D, Khan S. Withania somnifera (L.) Dunal (Ashwagandha) for the possible therapeutics and clinical management of SARS-CoV-2 infection: Plant-based drug discovery and targeted therapy. Front Cell Infect Microbiol 2022; 12:933824. [PMID: 36046742 PMCID: PMC9421373 DOI: 10.3389/fcimb.2022.933824] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2022] [Accepted: 07/11/2022] [Indexed: 11/23/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19) pandemic has killed huge populations throughout the world and acts as a high-risk factor for elderly and young immune-suppressed patients. There is a critical need to build up secure, reliable, and efficient drugs against to the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Bioactive compounds of Ashwagandha [Withania somnifera (L.) Dunal] may implicate as herbal medicine for the management and treatment of patients infected by SARS-CoV-2 infection. The aim of the current work is to update the knowledge of SARS-CoV-2 infection and information about the implication of various compounds of medicinal plant Withania somnifera with minimum side effects on the patients' organs. The herbal medicine Withania somnifera has an excellent antiviral activity that could be implicated in the management and treatment of flu and flu-like diseases connected with SARS-CoV-2. The analysis was performed by systematically re-evaluating the published articles related to the infection of SARS-CoV-2 and the herbal medicine Withania somnifera. In the current review, we have provided the important information and data of various bioactive compounds of Withania somnifera such as Withanoside V, Withanone, Somniferine, and some other compounds, which can possibly help in the management and treatment of SARS-CoV-2 infection. Withania somnifera has proved its potential for maintaining immune homeostasis of the body, inflammation regulation, pro-inflammatory cytokines suppression, protection of multiple organs, anti-viral, anti-stress, and anti-hypertensive properties. Withanoside V has the potential to inhibit the main proteases (Mpro) of SARS-CoV-2. At present, synthetic adjuvant vaccines are used against COVID-19. Available information showed the antiviral activity in Withanoside V of Withania somnifera, which may explore as herbal medicine against to SARS-CoV-2 infection after standardization of parameters of drug development and formulation in near future.
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Affiliation(s)
- Manali Singh
- Department of Biotechnology, Invertis University, Bareilly, Uttar Pradesh, India
- Department of Biochemistry, C.B.S.H, G.B Pant University of Agriculture and Technology, Pantnagar, Uttrakhand, India
| | - Kuldeep Jayant
- Department of Agricultural and Food Engineering, IIT Kharagpur, West Bengal, Kharagpur, India
| | - Dipti Singh
- Department of Biochemistry, C.B.S.H, G.B Pant University of Agriculture and Technology, Pantnagar, Uttrakhand, India
| | - Shivani Bhutani
- Department of Biotechnology, Invertis University, Bareilly, Uttar Pradesh, India
| | - Nitesh Kumar Poddar
- Department of Biosciences, Manipal University Jaipur, Jaipur, Rajasthan, India
| | - Anis Ahmad Chaudhary
- Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University, Riyadh, Saudi Arabia
| | - Salah-Ud-Din Khan
- Department of Biochemistry, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia
| | - Mohd Adnan
- Department of Biology, College of Science, University of Hail, Hail, Saudi Arabia
| | - Arif Jamal Siddiqui
- Department of Biology, College of Science, University of Hail, Hail, Saudi Arabia
| | - Md Imtaiyaz Hassan
- Center for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India
| | - Faez Iqbal Khan
- Department of Biological Sciences, School of Science, Xi’an Jiaotong-Liverpool University, Suzhou, China
- School of Electronic Science and Engineering, University of Electronic Science and Technology of China, Chengdu, China
| | - Dakun Lai
- School of Electronic Science and Engineering, University of Electronic Science and Technology of China, Chengdu, China
| | - Shahanavaj Khan
- Department of Health Sciences, Novel Global Community Educational Foundation 7 Peterlee Place, Hebersham, NSW, Australia
- Department of Medical Lab Technology, Indian Institute of Health and Technology (IIHT), Deoband, Saharanpur, UP, India
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
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Ouyang J, Zaongo SD, Harypursat V, Li X, Routy JP, Chen Y. SARS-CoV-2 pre-exposure prophylaxis: A potential COVID-19 preventive strategy for high-risk populations, including healthcare workers, immunodeficient individuals, and poor vaccine responders. Front Public Health 2022; 10:945448. [PMID: 36003629 PMCID: PMC9393547 DOI: 10.3389/fpubh.2022.945448] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 07/19/2022] [Indexed: 01/09/2023] Open
Abstract
The unprecedented worldwide spread of SARS-CoV-2 has imposed severe challenges on global health care systems. The roll-out and widespread administration of COVID-19 vaccines has been deemed a major milestone in the race to restrict the severity of the infection. Vaccines have as yet not entirely suppressed the relentless progression of the pandemic, due mainly to the emergence of new virus variants, and also secondary to the waning of protective antibody titers over time. Encouragingly, an increasing number of antiviral drugs, such as remdesivir and the newly developed drug combination, Paxlovid® (nirmatrelvir/ritonavir), as well as molnupiravir, have shown significant benefits for COVID-19 patient outcomes. Pre-exposure prophylaxis (PrEP) has been proven to be an effective preventive strategy in high-risk uninfected people exposed to HIV. Building on knowledge from what is already known about the use of PrEP for HIV disease, and from recently gleaned knowledge of antivirals used against COVID-19, we propose that SARS-CoV-2 PrEP, using specific antiviral and adjuvant drugs against SARS-CoV-2, may represent a novel preventive strategy for high-risk populations, including healthcare workers, immunodeficient individuals, and poor vaccine responders. Herein, we critically review the risk factors for severe COVID-19 and discuss PrEP strategies against SARS-CoV-2. In addition, we outline details of candidate anti-SARS-CoV-2 PrEP drugs, thus creating a framework with respect to the development of alternative and/or complementary strategies to prevent COVID-19, and contributing to the global armamentarium that has been developed to limit SARS-CoV-2 infection, severity, and transmission.
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Affiliation(s)
- Jing Ouyang
- Clinical Research Center, Chongqing Public Health Medical Center, Chongqing, China
| | - Silvere D. Zaongo
- Clinical Research Center, Chongqing Public Health Medical Center, Chongqing, China
| | - Vijay Harypursat
- Clinical Research Center, Chongqing Public Health Medical Center, Chongqing, China
| | - Xiaofang Li
- Clinical Research Center, Chongqing Public Health Medical Center, Chongqing, China
| | - Jean-Pierre Routy
- Infectious Diseases and Immunity in Global Health Program, Research Institute, McGill University Health Centre, Montréal, QC, Canada
- Chronic Viral Illness Service, McGill University Health Centre, Montréal, QC, Canada
- Division of Hematology, McGill University Health Centre, Montréal, QC, Canada
| | - Yaokai Chen
- Clinical Research Center, Chongqing Public Health Medical Center, Chongqing, China
- Division of Infectious Diseases, Chongqing Public Health Medical Center, Chongqing, China
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Melo-Filho CC, Bobrowski T, Martin HJ, Sessions Z, Popov KI, Moorman NJ, Baric RS, Muratov EN, Tropsha A. Conserved coronavirus proteins as targets of broad-spectrum antivirals. Antiviral Res 2022; 204:105360. [PMID: 35691424 PMCID: PMC9183392 DOI: 10.1016/j.antiviral.2022.105360] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Revised: 06/02/2022] [Accepted: 06/06/2022] [Indexed: 11/16/2022]
Abstract
Coronaviruses are a class of single-stranded, positive-sense RNA viruses that have caused three major outbreaks over the past two decades: Middle East respiratory syndrome-related coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). All outbreaks have been associated with significant morbidity and mortality. In this study, we have identified and explored conserved binding sites in the key coronavirus proteins for the development of broad-spectrum direct acting anti-coronaviral compounds and validated the significance of this conservation for drug discovery with existing experimental data. We have identified four coronaviral proteins with highly conserved binding site sequence and 3D structure similarity: PLpro, Mpro, nsp10-nsp16 complex(methyltransferase), and nsp15 endoribonuclease. We have compiled all available experimental data for known antiviral medications inhibiting these targets and identified compounds active against multiple coronaviruses. The identified compounds representing potential broad-spectrum antivirals include: GC376, which is active against six viral Mpro (out of six tested, as described in research literature); mycophenolic acid, which is active against four viral PLpro (out of four); and emetine, which is active against four viral RdRp (out of four). The approach described in this study for coronaviruses, which combines the assessment of sequence and structure conservation across a viral family with the analysis of accessible chemical structure - antiviral activity data, can be explored for the development of broad-spectrum drugs for multiple viral families.
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Affiliation(s)
- Cleber C Melo-Filho
- Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, 27599, USA
| | - Tesia Bobrowski
- Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, 27599, USA
| | - Holli-Joi Martin
- Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, 27599, USA
| | - Zoe Sessions
- Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, 27599, USA
| | - Konstantin I Popov
- Department of Biochemistry and Biophysics, School of Medicine, University of North Carolina, Chapel Hill, NC, 27599, USA
| | - Nathaniel J Moorman
- Department of Microbiology and Immunology, School of Medicine, University of North Carolina, Chapel Hill, NC, 27599, USA
| | - Ralph S Baric
- Department of Epidemiology, Gillings School of Public Health, University of North Carolina, Chapel Hill, NC, 27599, USA
| | - Eugene N Muratov
- Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, 27599, USA.
| | - Alexander Tropsha
- Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, 27599, USA.
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Chiu W, Verschueren L, Van den Eynde C, Buyck C, De Meyer S, Jochmans D, Bojkova D, Ciesek S, Cinatl J, De Jonghe S, Leyssen P, Neyts J, Van Loock M, Van Damme E. Development and optimization of a high-throughput screening assay for in vitro anti-SARS-CoV-2 activity: Evaluation of 5676 Phase 1 Passed Structures. J Med Virol 2022; 94:3101-3111. [PMID: 35229317 PMCID: PMC9088669 DOI: 10.1002/jmv.27683] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Revised: 02/25/2022] [Accepted: 02/27/2022] [Indexed: 01/09/2023]
Abstract
Although vaccines are currently used to control the coronavirus disease 2019 (COVID-19) pandemic, treatment options are urgently needed for those who cannot be vaccinated and for future outbreaks involving new severe acute respiratory syndrome coronavirus virus 2 (SARS-CoV-2) strains or coronaviruses not covered by current vaccines. Thus far, few existing antivirals are known to be effective against SARS-CoV-2 and clinically successful against COVID-19. As part of an immediate response to the COVID-19 pandemic, a high-throughput, high content imaging-based SARS-CoV-2 infection assay was developed in VeroE6 African green monkey kidney epithelial cells expressing a stable enhanced green fluorescent protein (VeroE6-eGFP cells) and was used to screen a library of 5676 compounds that passed Phase 1 clinical trials. Eight drugs (nelfinavir, RG-12915, itraconazole, chloroquine, hydroxychloroquine, sematilide, remdesivir, and doxorubicin) were identified as inhibitors of in vitro anti-SARS-CoV-2 activity in VeroE6-eGFP and/or Caco-2 cell lines. However, apart from remdesivir, toxicity and pharmacokinetic data did not support further clinical development of these compounds for COVID-19 treatment.
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Affiliation(s)
- Winston Chiu
- KU Leuven, Department of Microbiology, Immunology and TransplantationRega Institute, Laboratory of Virology and ChemotherapyLeuvenBelgium
| | | | | | | | | | - Dirk Jochmans
- KU Leuven, Department of Microbiology, Immunology and TransplantationRega Institute, Laboratory of Virology and ChemotherapyLeuvenBelgium
| | - Denisa Bojkova
- Institute of Medical VirologyUniversity Hospital Frankfurt, Goethe UniversityFrankfurt am MainGermany
| | - Sandra Ciesek
- Institute of Medical VirologyUniversity Hospital Frankfurt, Goethe UniversityFrankfurt am MainGermany
| | - Jindrich Cinatl
- Institute of Medical VirologyUniversity Hospital Frankfurt, Goethe UniversityFrankfurt am MainGermany
| | - Steven De Jonghe
- KU Leuven, Department of Microbiology, Immunology and TransplantationRega Institute, Laboratory of Virology and ChemotherapyLeuvenBelgium
| | - Pieter Leyssen
- KU Leuven, Department of Microbiology, Immunology and TransplantationRega Institute, Laboratory of Virology and ChemotherapyLeuvenBelgium
| | - Johan Neyts
- KU Leuven, Department of Microbiology, Immunology and TransplantationRega Institute, Laboratory of Virology and ChemotherapyLeuvenBelgium
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Barman RK, Mukhopadhyay A, Maulik U, Das S. A network biology approach to identify crucial host targets for COVID-19. Methods 2022; 203:108-115. [PMID: 35364279 PMCID: PMC8960288 DOI: 10.1016/j.ymeth.2022.03.016] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Revised: 03/09/2022] [Accepted: 03/27/2022] [Indexed: 12/23/2022] Open
Abstract
The ongoing global pandemic of COVID-19, caused by SARS-CoV-2 has killed more than 5.9 million individuals out of ∼43 million confirmed infections. At present, several parts of the world are encountering the 3rd wave. Mass vaccination has been started in several countries but they are less likely to be broadly available for the current pandemic, repurposing of the existing drugs has drawn highest attention for an immediate solution. A recent publication has mapped the physical interactions of SARS-CoV-2 and human proteins by affinity-purification mass spectrometry (AP-MS) and identified 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Here, we taken a network biology approach and constructed a human protein-protein interaction network (PPIN) with the above SARS-CoV-2 targeted proteins. We utilized a combination of essential network centrality measures and functional properties of the human proteins to identify the critical human targets of SARS-CoV-2. Four human proteins, namely PRKACA, RHOA, CDK5RAP2, and CEP250 have emerged as the best therapeutic targets, of which PRKACA and CEP250 were also found by another group as potential candidates for drug targets in COVID-19. We further found candidate drugs/compounds, such as guanosine triphosphate, remdesivir, adenosine monophosphate, MgATP, and H-89 dihydrochloride that bind the target human proteins. The urgency to prevent the spread of infection and the death of diseased individuals has prompted the search for agents from the pool of approved drugs to repurpose them for COVID-19. Our results indicate that host targeting therapy with the repurposed drugs may be a useful strategy for the treatment of SARS-CoV-2 infection.
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Affiliation(s)
- Ranjan Kumar Barman
- Division of Virology, ICMR-National Institute of Cholera and Enteric Diseases, Kolkata 700010, India; Department of Computer Science and Engineering, Jadavpur University, Kolkata 700032, India
| | - Anirban Mukhopadhyay
- Department of Computer Science and Engineering, University of Kalyani, Kalyani 741235, West Bengal, India
| | - Ujjwal Maulik
- Department of Computer Science and Engineering, Jadavpur University, Kolkata 700032, India
| | - Santasabuj Das
- Division of Clinical Medicine, ICMR-National Institute of Cholera and Enteric Diseases, Kolkata 700010, India; ICMR-National Institute of Occupational Health, Ahmedabad 380016, India.
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Chakrabartty I, Khan M, Mahanta S, Chopra H, Dhawan M, Choudhary OP, Bibi S, Mohanta YK, Emran TB. Comparative overview of emerging RNA viruses: Epidemiology, pathogenesis, diagnosis and current treatment. Ann Med Surg (Lond) 2022; 79:103985. [PMID: 35721786 PMCID: PMC9188442 DOI: 10.1016/j.amsu.2022.103985] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Revised: 06/07/2022] [Accepted: 06/08/2022] [Indexed: 02/06/2023] Open
Abstract
From many decades, emerging infections have threatened humanity. The pandemics caused by different CoVs have already claimed and will continue to claim millions of lives. The SARS, Ebola, MERS epidemics and the most recent emergence of COVID-19 pandemic have threatened populations across borders. Since a highly pathogenic CoV has been evolved into the human population in the twenty-first century known as SARS, scientific advancements and innovative methods to tackle these viruses have increased in order to improve response preparedness towards the unpredictable threat posed by these rapidly emerging pathogens. Recently published review articles on SARS-CoV-2 have mainly focused on its pathogenesis, epidemiology and available treatments. However, in this review, we have done a systematic comparison of all three CoVs i.e., SARS, MERS and SARS-CoV-2 along with Ebola and Zika in terms of their epidemiology, virology, clinical features and current treatment strategies. This review focuses on important emerging RNA viruses starting from Zika, Ebola and the CoVs which include SARS, MERS and SARS-CoV-2. Each of these viruses has been elaborated on the basis of their epidemiology, virulence, transmission and treatment. However, special attention has been given to SARS-CoV-2 and the disease caused by it i.e., COVID-19 due to current havoc caused worldwide. At the end, insights into the current understanding of the lessons learned from previous epidemics to combat emerging CoVs have been described. The travel-related viral spread, the unprecedented nosocomial outbreaks and the high case-fatality rates associated with these highly transmissible and pathogenic viruses highlight the need for new prophylactic and therapeutic actions which include but are not limited to clinical indicators, contact tracing, and laboratory investigations as important factors that need to be taken into account in order to arrive at the final conclusion.
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Affiliation(s)
- Ishani Chakrabartty
- Department of Applied Biology, School of Biological Sciences, University of Science and Technology Meghalaya (USTM), 9th Mile, Techno City, Baridua, Ri-Bhoi 793101, Meghalaya, India
| | - Maryam Khan
- Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, 202002, U.P, India
| | - Saurov Mahanta
- National Institute of Electronics and Information Technology (NIELIT), Guwahati Centre Guwahati, 781008, Assam, India
| | - Hitesh Chopra
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India
| | - Manish Dhawan
- Department of Microbiology, Punjab Agricultural University, Ludhiana, 141004, Punjab, India
- Trafford College, Altrincham, Manchester, WA14 5PQ, UK
| | - Om Prakash Choudhary
- Department of Veterinary Anatomy and Histology, College of Veterinary Sciences and Animal Husbandry, Central Agricultural University (I), Selesih, Aizawl, India
| | - Shabana Bibi
- Department of Biosciences, Shifa Tameer-e-Millat University, Islamabad, Pakistan
- Yunnan Herbal Laboratory, College of Ecology and Environmental Sciences, Yunnan University, Kunming, 650091, China
| | - Yugal Kishore Mohanta
- Department of Applied Biology, School of Biological Sciences, University of Science and Technology Meghalaya (USTM), 9th Mile, Techno City, Baridua, Ri-Bhoi 793101, Meghalaya, India
| | - Talha Bin Emran
- Department of Pharmacy, BGC Trust University Bangladesh, Chittagong, 4381, Bangladesh
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, 1207, Bangladesh
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In Silico Screening of Novel TMPRSS2 Inhibitors for Treatment of COVID-19. Molecules 2022; 27:molecules27134210. [PMID: 35807455 PMCID: PMC9268035 DOI: 10.3390/molecules27134210] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Revised: 06/28/2022] [Accepted: 06/28/2022] [Indexed: 02/04/2023] Open
Abstract
COVID-19, a pandemic caused by the virus SARS-CoV-2, has spread globally, necessitating the search for antiviral compounds. Transmembrane protease serine 2 (TMPRSS2) is a cell surface protease that plays an essential role in SARS-CoV-2 infection. Therefore, researchers are searching for TMPRSS2 inhibitors that can be used for the treatment of COVID-19. As such, in this study, based on the crystal structure, we targeted the active site of TMPRSS2 for virtual screening of compounds in the FDA database. Then, we screened lumacaftor and ergotamine, which showed strong binding ability, using 100 ns molecular dynamics simulations to study the stability of the protein–ligand binding process, the flexibility of amino acid residues, and the formation of hydrogen bonds. Subsequently, we calculated the binding free energy of the protein–ligand complex by the MM-PBSA method. The results show that lumacaftor and ergotamine interact with residues around the TMPRSS2 active site, and reached equilibrium in the 100 ns molecular dynamics simulations. We think that lumacaftor and ergotamine, which we screened through in silico studies, can effectively inhibit the activity of TMPRSS2. Our findings provide a basis for subsequent in vitro experiments, having important implications for the development of effective anti-COVID-19 drugs.
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Calvo-Alvarez E, Dolci M, Perego F, Signorini L, Parapini S, D’Alessandro S, Denti L, Basilico N, Taramelli D, Ferrante P, Delbue S. Antiparasitic Drugs against SARS-CoV-2: A Comprehensive Literature Survey. Microorganisms 2022; 10:1284. [PMID: 35889004 PMCID: PMC9320270 DOI: 10.3390/microorganisms10071284] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 06/10/2022] [Accepted: 06/13/2022] [Indexed: 01/09/2023] Open
Abstract
More than two years have passed since the viral outbreak that led to the novel infectious respiratory disease COVID-19, caused by the SARS-CoV-2 coronavirus. Since then, the urgency for effective treatments resulted in unprecedented efforts to develop new vaccines and to accelerate the drug discovery pipeline, mainly through the repurposing of well-known compounds with broad antiviral effects. In particular, antiparasitic drugs historically used against human infections due to protozoa or helminth parasites have entered the main stage as a miracle cure in the fight against SARS-CoV-2. Despite having demonstrated promising anti-SARS-CoV-2 activities in vitro, conflicting results have made their translation into clinical practice more difficult than expected. Since many studies involving antiparasitic drugs are currently under investigation, the window of opportunity might be not closed yet. Here, we will review the (controversial) journey of these old antiparasitic drugs to combat the human infection caused by the novel coronavirus SARS-CoV-2.
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Affiliation(s)
- Estefanía Calvo-Alvarez
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy; (M.D.); (F.P.); (L.S.); (L.D.); (N.B.); (P.F.); (S.D.)
| | - Maria Dolci
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy; (M.D.); (F.P.); (L.S.); (L.D.); (N.B.); (P.F.); (S.D.)
| | - Federica Perego
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy; (M.D.); (F.P.); (L.S.); (L.D.); (N.B.); (P.F.); (S.D.)
| | - Lucia Signorini
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy; (M.D.); (F.P.); (L.S.); (L.D.); (N.B.); (P.F.); (S.D.)
| | - Silvia Parapini
- Department of Biomedical Sciences for Health, University of Milan, 20133 Milan, Italy;
| | - Sarah D’Alessandro
- Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy; (S.D.); (D.T.)
| | - Luca Denti
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy; (M.D.); (F.P.); (L.S.); (L.D.); (N.B.); (P.F.); (S.D.)
| | - Nicoletta Basilico
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy; (M.D.); (F.P.); (L.S.); (L.D.); (N.B.); (P.F.); (S.D.)
| | - Donatella Taramelli
- Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy; (S.D.); (D.T.)
| | - Pasquale Ferrante
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy; (M.D.); (F.P.); (L.S.); (L.D.); (N.B.); (P.F.); (S.D.)
| | - Serena Delbue
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy; (M.D.); (F.P.); (L.S.); (L.D.); (N.B.); (P.F.); (S.D.)
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Baigent C, Windecker S, Andreini D, Arbelo E, Barbato E, Bartorelli AL, Baumbach A, Behr ER, Berti S, Bueno H, Capodanno D, Cappato R, Chieffo A, Collet JP, Cuisset T, de Simone G, Delgado V, Dendale P, Dudek D, Edvardsen T, Elvan A, González-Juanatey JR, Gori M, Grobbee D, Guzik TJ, Halvorsen S, Haude M, Heidbuchel H, Hindricks G, Ibanez B, Karam N, Katus H, Klok FA, Konstantinides SV, Landmesser U, Leclercq C, Leonardi S, Lettino M, Marenzi G, Mauri J, Metra M, Morici N, Mueller C, Petronio AS, Polovina MM, Potpara T, Praz F, Prendergast B, Prescott E, Price S, Pruszczyk P, Rodríguez-Leor O, Roffi M, Romaguera R, Rosenkranz S, Sarkozy A, Scherrenberg M, Seferovic P, Senni M, Spera FR, Stefanini G, Thiele H, Tomasoni D, Torracca L, Touyz RM, Wilde AA, Williams B. ESC guidance for the diagnosis and management of cardiovascular disease during the COVID-19 pandemic: part 2-care pathways, treatment, and follow-up. Cardiovasc Res 2022; 118:1618-1666. [PMID: 34864876 PMCID: PMC8690236 DOI: 10.1093/cvr/cvab343] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
AIMS Since its emergence in early 2020, the novel severe acute respiratory syndrome coronavirus 2 causing coronavirus disease 2019 (COVID-19) has reached pandemic levels, and there have been repeated outbreaks across the globe. The aim of this two part series is to provide practical knowledge and guidance to aid clinicians in the diagnosis and management of cardiovascular (CV) disease in association with COVID-19. METHODS AND RESULTS A narrative literature review of the available evidence has been performed, and the resulting information has been organized into two parts. The first, which was reported previously, focused on the epidemiology, pathophysiology, and diagnosis of CV conditions that may be manifest in patients with COVID-19. This second part addresses the topics of: care pathways and triage systems and management and treatment pathways, both of the most commonly encountered CV conditions and of COVID-19; and information that may be considered useful to help patients with CV disease (CVD) to avoid exposure to COVID-19. CONCLUSION This comprehensive review is not a formal guideline but rather a document that provides a summary of current knowledge and guidance to practicing clinicians managing patients with CVD and COVID-19. The recommendations are mainly the result of observations and personal experience from healthcare providers. Therefore, the information provided here may be subject to change with increasing knowledge, evidence from prospective studies, and changes in the pandemic. Likewise, the guidance provided in the document should not interfere with recommendations provided by local and national healthcare authorities.
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Mahmud N, Anik MI, Hossain MK, Khan MI, Uddin S, Ashrafuzzaman M, Rahaman MM. Advances in Nanomaterial-Based Platforms to Combat COVID-19: Diagnostics, Preventions, Therapeutics, and Vaccine Developments. ACS APPLIED BIO MATERIALS 2022; 5:2431-2460. [PMID: 35583460 PMCID: PMC9128020 DOI: 10.1021/acsabm.2c00123] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Accepted: 04/24/2022] [Indexed: 12/12/2022]
Abstract
The COVID-19 pandemic caused by the SARS-CoV-2, a ribonucleic acid (RNA) virus that emerged less than two years ago but has caused nearly 6.1 million deaths to date. Recently developed variants of the SARS-CoV-2 virus have been shown to be more potent and expanded at a faster rate. Until now, there is no specific and effective treatment for SARS-CoV-2 in terms of reliable and sustainable recovery. Precaution, prevention, and vaccinations are the only ways to keep the pandemic situation under control. Medical and scientific professionals are now focusing on the repurposing of previous technology and trying to develop more fruitful methodologies to detect the presence of viruses, treat the patients, precautionary items, and vaccine developments. Nanomedicine or nanobased platforms can play a crucial role in these fronts. Researchers are working on many effective approaches by nanosized particles to combat SARS-CoV-2. The role of a nanobased platform to combat SARS-CoV-2 is extremely diverse (i.e., mark to personal protective suit, rapid diagnostic tool to targeted treatment, and vaccine developments). Although there are many theoretical possibilities of a nanobased platform to combat SARS-CoV-2, until now there is an inadequate number of research targeting SARS-CoV-2 to explore such scenarios. This unique mini-review aims to compile and elaborate on the recent advances of nanobased approaches from prevention, diagnostics, treatment to vaccine developments against SARS-CoV-2, and associated challenges.
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Affiliation(s)
- Niaz Mahmud
- Department of Biomedical Engineering,
Military Institute of Science and Technology, Dhaka 1216,
Bangladesh
| | - Muzahidul I. Anik
- Department of Chemical Engineering,
University of Rhode Island, Kingston, Rhode Island 02881,
United States
| | - M. Khalid Hossain
- Interdisciplinary Graduate School of Engineering
Science, Kyushu University, Fukuoka 816-8580,
Japan
- Atomic Energy Research Establishment,
Bangladesh Atomic Energy Commission, Dhaka 1349,
Bangladesh
| | - Md Ishak Khan
- Department of Neurosurgery, University of
Pennsylvania, Philadelphia, Pennsylvania 19104, United
States
| | - Shihab Uddin
- Department of Applied Chemistry, Graduate School of
Engineering, Kyushu University, Fukuoka 819-0395,
Japan
- Department of Chemical Engineering,
Massachusetts Institute of Technology, Cambridge
Massachusetts 02139, United States
| | - Md. Ashrafuzzaman
- Department of Biomedical Engineering,
Military Institute of Science and Technology, Dhaka 1216,
Bangladesh
| | - Md Mushfiqur Rahaman
- Department of Emergency Medicine, NYU
Langone Health, New York, New York 10016, United
States
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49
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Chlorpromazine, a Clinically Approved Drug, Inhibits SARS-CoV-2 Nucleocapsid-Mediated Induction of IL-6 in Human Monocytes. Molecules 2022; 27:molecules27123651. [PMID: 35744777 PMCID: PMC9228867 DOI: 10.3390/molecules27123651] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Revised: 05/31/2022] [Accepted: 06/03/2022] [Indexed: 01/08/2023] Open
Abstract
The COVID-19 pandemic, caused by the rapidly spreading SARS-CoV-2 virus, led to the unprecedented mobilization of scientists, resulting in the rapid development of vaccines and potential pharmaceuticals. Although COVID-19 symptoms are moderately severe in most people, in some cases the disease can result in pneumonia and acute respiratory failure as well as can be fatal. The severe course of COVID-19 is associated with a hyperinflammatory state called a cytokine storm. One of the key cytokines creating a proinflammatory environment is IL-6, which is secreted mainly by monocytes and macrophages. Therefore, this cytokine has become a target for some therapies that inhibit its biological action; however, these therapies are expensive, and their availability is limited in poorer countries. Thus, new cheaper drugs that can overcome the severe infections of COVID-19 are needed. Here, we show that chlorpromazine inhibits the expression and secretion of IL-6 by monocytes activated by SARS-CoV-2 virus nucleocapsid protein and affects the activity of NF-κB and MEK/ERK signaling. Our results, including others, indicate that chlorpromazine, which has been used for several decades as a neuroleptic, exerts antiviral and immunomodulatory activity, is safe and inexpensive, and might be a desirable drug to support the therapy of patients with COVID-19.
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50
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Roncato R, Angelini J, Pani A, Talotta R. Lipid rafts as viral entry routes and immune platforms: A double-edged sword in SARS-CoV-2 infection? Biochim Biophys Acta Mol Cell Biol Lipids 2022; 1867:159140. [PMID: 35248801 PMCID: PMC8894694 DOI: 10.1016/j.bbalip.2022.159140] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 02/13/2022] [Accepted: 02/25/2022] [Indexed: 12/15/2022]
Abstract
Lipid rafts are nanoscopic compartments of cell membranes that serve a variety of biological functions. They play a crucial role in viral infections, as enveloped viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can exploit rafts to enter or quit target cells. On the other hand, lipid rafts contribute to the formation of immune synapses and their proper functioning is a prerequisite for adequate immune response and viral clearance. In this narrative review we dissect the panorama focusing on this singular aspect of cell biology in the context of SARS-CoV-2 infection and therapy. A lipid raft-mediated mechanism can be hypothesized for many drugs recommended or considered for the treatment of SARS-CoV-2 infection, such as glucocorticoids, antimalarials, immunosuppressants and antiviral agents. Furthermore, the additional use of lipid-lowering agents, like statins, may affect the lipid composition of membrane rafts and thus influence the processes occurring in these compartments. The combination of drugs acting on lipid rafts may be successful in the treatment of more severe forms of the disease and should be reserved for further investigation.
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Affiliation(s)
- Rossana Roncato
- Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), Istituto di Ricovero e Cura a carattere Scientifico (IRCCS), via Gallini, 33081 Aviano (PN), Italy
| | - Jacopo Angelini
- Clinical Pharmacology Institute, Azienda Sanitaria Universitaria Friuli Centrale (ASU FC), via Pozzuolo, 33100 Udine, Italy
| | - Arianna Pani
- Toxicology Department of Oncology and Hemato-Oncology, University of Milan, via Vanvitelli, 20133 Milan, Italy
| | - Rossella Talotta
- Department of Clinical and Experimental Medicine, Rheumatology Unit, AOU "Gaetano Martino", University of Messina, 98100 Messina, Italy
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