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Oates RN, Lieu LB, Srzentić K, Damoc E, Fornelli L. Characterization of a Monoclonal Antibody by Native and Denaturing Top-Down Mass Spectrometry. JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY 2024; 35:2197-2208. [PMID: 39105725 PMCID: PMC11774622 DOI: 10.1021/jasms.4c00224] [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] [Indexed: 08/07/2024]
Abstract
Established in recent years as an important approach to unraveling the heterogeneity of intact monoclonal antibodies, native mass spectrometry has been rarely utilized for sequencing these complex biomolecules via tandem mass spectrometry. Typically, top-down mass spectrometry has been performed starting from highly charged precursor ions obtained via electrospray ionization under denaturing conditions (i.e., in the presence of organic solvents and acidic pH). Here we systematically benchmark four distinct ion dissociation methods─namely, higher-energy collisional dissociation, electron transfer dissociation, electron transfer dissociation/higher-energy collisional dissociation, and 213 nm ultraviolet photodissociation─in their capability to characterize a therapeutic monoclonal antibody, trastuzumab, starting from denatured and native-like precursor ions. Interestingly, native top-down mass spectrometry results in higher sequence coverage than the experiments carried out under denaturing conditions, with the exception of ultraviolet photodissociation. Globally, electron transfer dissociation followed by collision-based activation of product ions generates the largest number of backbone cleavages in disulfide protected regions, including the complementarity determining regions, regardless of electrospray ionization conditions. Overall, these findings suggest that native mass spectrometry can certainly be used for the gas-phase sequencing of whole monoclonal antibodies, although the dissociation of denatured precursor ions still returns a few backbone cleavages not identified in native experiments. Finally, a comparison of the fragmentation maps obtained under denaturing and native conditions strongly points toward disulfide bonds as the primary reason behind the largely overlapping dissociation patterns.
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Affiliation(s)
- Ryan N. Oates
- Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK, 73019 USA
| | - Linda B. Lieu
- Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK, 73019 USA
| | | | - Eugen Damoc
- Thermo Fisher Scientific, Bremen, DE-HB 28199 Germany
| | - Luca Fornelli
- Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK, 73019 USA
- School of Biological Sciences, University of Oklahoma, Norman, OK, 73019 USA
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Alqahtani SAM. Mucosal immunity in COVID-19: a comprehensive review. Front Immunol 2024; 15:1433452. [PMID: 39206184 PMCID: PMC11349522 DOI: 10.3389/fimmu.2024.1433452] [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: 05/15/2024] [Accepted: 07/19/2024] [Indexed: 09/04/2024] Open
Abstract
Mucosal immunity plays a crucial role in defending against coronaviruses, particularly at respiratory sites, serving as the first line of defense against viral invasion and replication. Coronaviruses have developed various immune evasion strategies at the mucosal immune system, hindering the recognition of infected cells and evading antibody responses. Understanding the immune mechanisms and responses is crucial for developing effective vaccines and therapeutics against coronaviruses. The role of mucosal immunity in COVID-19 is significant, influencing both local and systemic immune responses to the virus. Although most clinical studies focus on antibodies and cellular immunity in peripheral blood, mucosal immune responses in the respiratory tract play a key role in the early restriction of viral replication and the clearance of SARS-CoV-2. Identification of mucosal biomarkers associated with viral clearance will allow monitoring of infection-induced immunity. Mucosally delivered vaccines and those under clinical trials are being compared and contrasted to understand their effectiveness in inducing mucosal immunity against coronaviruses. A greater understanding of lung tissue-based immunity may lead to improved diagnostic and prognostic procedures and novel treatment strategies aimed at reducing the disease burden of community-acquired pneumonia, avoiding the systemic manifestations of infection and excess morbidity and mortality. This comprehensive review article outlines the current evidence about the role of mucosal immune responses in the clearance of SARS-CoV-2 infection, as well as potential mucosal mechanisms of protection against (re-)infection. It also proposes that there is a significant role for mucosal immunity and for secretory as well as circulating IgA antibodies in COVID-19, and that it is important to elucidate this in order to comprehend especially the asymptomatic and mild states of the infection, which appear to account for the majority of cases. Moreover, it is possible that mucosal immunity can be exploited for beneficial diagnostic, therapeutic, or prophylactic purposes. The findings from recent studies on mucosal immunity in COVID-19 can be used to develop effective vaccines and treatments that can effectively target both mucosal and systemic immune responses.
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Rurek M. Mitochondria in COVID-19: from cellular and molecular perspective. Front Physiol 2024; 15:1406635. [PMID: 38974521 PMCID: PMC11224649 DOI: 10.3389/fphys.2024.1406635] [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: 03/25/2024] [Accepted: 05/27/2024] [Indexed: 07/09/2024] Open
Abstract
The rapid development of the COVID-19 pandemic resulted in a closer analysis of cell functioning during β-coronavirus infection. This review will describe evidence for COVID-19 as a syndrome with a strong, albeit still underestimated, mitochondrial component. Due to the sensitivity of host mitochondria to coronavirus infection, SARS-CoV-2 affects mitochondrial signaling, modulates the immune response, modifies cellular energy metabolism, induces apoptosis and ageing, worsening COVID-19 symptoms which can sometimes be fatal. Various aberrations across human systems and tissues and their relationships with mitochondria were reported. In this review, particular attention is given to characterization of multiple alterations in gene expression pattern and mitochondrial metabolism in COVID-19; the complexity of interactions between SARS-CoV-2 and mitochondrial proteins is presented. The participation of mitogenome fragments in cell signaling and the occurrence of SARS-CoV-2 subgenomic RNA within membranous compartments, including mitochondria is widely discussed. As SARS-CoV-2 severely affects the quality system of mitochondria, the cellular background for aberrations in mitochondrial dynamics in COVID-19 is additionally characterized. Finally, perspectives on the mitigation of COVID-19 symptoms by affecting mitochondrial biogenesis by numerous compounds and therapeutic treatments are briefly outlined.
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Affiliation(s)
- Michał Rurek
- Department of Molecular and Cellular Biology, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Poznań, Poland
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Kumar S, Dasgupta S, Sajadi MM, Snyder GA, DeVico AL, Ray K. Discordant Antigenic Properties of Soluble and Virion SARS-CoV-2 Spike Proteins. Viruses 2024; 16:407. [PMID: 38543772 PMCID: PMC10974403 DOI: 10.3390/v16030407] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Revised: 02/20/2024] [Accepted: 02/26/2024] [Indexed: 04/01/2024] Open
Abstract
Efforts to develop vaccine and immunotherapeutic countermeasures against the COVID-19 pandemic focus on targeting the trimeric spike (S) proteins of SARS-CoV-2. Vaccines and therapeutic design strategies must impart the characteristics of virion S from historical and emerging variants onto practical constructs such as soluble, stabilized trimers. The virus spike is a heterotrimer of two subunits: S1, which includes the receptor binding domain (RBD) that binds the cell surface receptor ACE2, and S2, which mediates membrane fusion. Previous studies suggest that the antigenic, structural, and functional characteristics of virion S may differ from current soluble surrogates. For example, it was reported that certain anti-glycan, HIV-1 neutralizing monoclonal antibodies bind soluble SARS-CoV-2 S but do not neutralize SARS-CoV-2 virions. In this study, we used single-molecule fluorescence correlation spectroscopy (FCS) under physiologically relevant conditions to examine the reactivity of broadly neutralizing and non-neutralizing anti-S human monoclonal antibodies (mAbs) isolated in 2020. Binding efficiency was assessed by FCS with soluble S trimers, pseudoviruses and inactivated wild-type virions representing variants emerging from 2020 to date. Anti-glycan mAbs were tested and compared. We find that both anti-S specific and anti-glycan mAbs exhibit variable but efficient binding to a range of stabilized, soluble trimers. Across mAbs, the efficiencies of soluble S binding were positively correlated with reactivity against inactivated virions but not pseudoviruses. Binding efficiencies with pseudoviruses were generally lower than with soluble S or inactivated virions. Among neutralizing mAbs, potency did not correlate with binding efficiencies on any target. No neutralizing activity was detected with anti-glycan antibodies. Notably, the virion S released from membranes by detergent treatment gained more efficient reactivity with anti-glycan, HIV-neutralizing antibodies but lost reactivity with all anti-S mAbs. Collectively, the FCS binding data suggest that virion surfaces present appreciable amounts of both functional and nonfunctional trimers, with neutralizing anti-S favoring the former structures and non-neutralizing anti-glycan mAbs binding the latter. S released from solubilized virions represents a nonfunctional structure bound by anti-glycan mAbs, while engineered soluble trimers present a composite structure that is broadly reactive with both mAb types. The detection of disparate antigenicity and immunoreactivity profiles in engineered and virion-associated S highlight the value of single-virus analyses in designing future antiviral strategies against SARS-CoV-2.
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Affiliation(s)
- Sameer Kumar
- Division of Vaccine Research, Institute of Human Virology, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD 21201, USA
| | - Souradip Dasgupta
- Division of Vaccine Research, Institute of Human Virology, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD 21201, USA
| | - Mohammad M. Sajadi
- Division of Vaccine Research, Institute of Human Virology, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD 21201, USA
- Division of Clinical Research, Institute of Human Virology, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD 21201, USA
- Department of Medicine, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD 21201, USA
| | - Greg A. Snyder
- Division of Vaccine Research, Institute of Human Virology, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD 21201, USA
- Department of Medicine, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD 21201, USA
| | - Anthony L. DeVico
- Division of Vaccine Research, Institute of Human Virology, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD 21201, USA
- Department of Medicine, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD 21201, USA
| | - Krishanu Ray
- Division of Vaccine Research, Institute of Human Virology, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD 21201, USA
- Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD 21201, USA
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Park SJ, Jang MS, Lim KH, Seo JW, Im WJ, Han KH, Kim SE, Jang E, Park D, Kim YB. Preclinical evaluation of general toxicity and safety pharmacology of a receptor-binding domain-based COVID-19 subunit vaccine in various animal models. Arch Toxicol 2023; 97:2429-2440. [PMID: 37491472 DOI: 10.1007/s00204-023-03549-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Accepted: 06/14/2023] [Indexed: 07/27/2023]
Abstract
The coronavirus disease 2019 pandemic has resulted in the introduction of several naïve methods of vaccine development, which have been used to prepare novel viral vectors and mRNA-based vaccines. However, reluctance to receive vaccines owing to the uncertainty regarding their safety is prevalent. Therefore, rigorous safety evaluation of vaccines through preclinical toxicity studies is critical to determine the safety profiles of vaccine candidates. This study aimed to evaluate the toxicity profile of HuVac-19, a subunit vaccine of SARS-CoV-2 utilizing the receptor-binding domain as an antigen, in rats, rabbits, and dogs using single- and repeat-dose study designs. Repeat-dose toxicity studies in rats and rabbits showed transient changes in hematological and serum biochemical parameters in the adjuvant and/or vaccine groups; however, these changes were reversed or potentially reversible after the recovery period. Moreover, temporary reversible changes in absolute and relative organ weights were observed in the prostate of rats and the thymus of rabbits. Gross examination of the injection sites in rats and rabbits treated with the adjuvant- and HuVac-19 showed discoloration and foci, whereas histopathological examination showed granulomatous inflammation, inflammatory cell infiltration, and myofiber degeneration/necrosis. This inflammatory response was local, unassociated with other toxicological changes, and resolved. In a pharmacological safety study, no toxicological or physiological changes associated with HuVac-19 administration were observed. In conclusion, HuVac-19 was not associated with any major systemic adverse effects in the general toxicity and safety pharmacology evaluation, demonstrating that HuVac-19 is a vaccine candidate with sufficient capacity to be used in human clinical trials.
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Affiliation(s)
- Sang-Jin Park
- Korea Institute of Toxicology, 141 Gaejeongro, Yuseong-gu, Daejeon, 34114, Republic of Korea
| | - Min Seong Jang
- Korea Institute of Toxicology, 141 Gaejeongro, Yuseong-gu, Daejeon, 34114, Republic of Korea
| | - Kwang-Hyun Lim
- Korea Institute of Toxicology, 141 Gaejeongro, Yuseong-gu, Daejeon, 34114, Republic of Korea
| | - Joung-Wook Seo
- Korea Institute of Toxicology, 141 Gaejeongro, Yuseong-gu, Daejeon, 34114, Republic of Korea
| | - Wan-Jung Im
- Korea Institute of Toxicology, 141 Gaejeongro, Yuseong-gu, Daejeon, 34114, Republic of Korea
| | - Kang-Hyun Han
- Korea Institute of Toxicology, 141 Gaejeongro, Yuseong-gu, Daejeon, 34114, Republic of Korea
| | - Seong-Eun Kim
- HuVet Bio, Inc., 127 Beubwon-ro, Songpa gu, Seoul, 05836, Republic of Korea
| | - Eunhee Jang
- HuVet Bio, Inc., 127 Beubwon-ro, Songpa gu, Seoul, 05836, Republic of Korea
| | - Danbi Park
- HuVet Bio, Inc., 127 Beubwon-ro, Songpa gu, Seoul, 05836, Republic of Korea
| | - Yong-Bum Kim
- Korea Institute of Toxicology, 141 Gaejeongro, Yuseong-gu, Daejeon, 34114, Republic of Korea.
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Alipour S, Mahmoudi L, Ahmadi F. Pulmonary drug delivery: an effective and convenient delivery route to combat COVID-19. Drug Deliv Transl Res 2023; 13:705-715. [PMID: 36260223 PMCID: PMC9580423 DOI: 10.1007/s13346-022-01251-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/09/2022] [Indexed: 02/05/2023]
Abstract
The recent outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China has spread rapidly around the world, leading to a widespread and urgent effort to develop and use comprehensive approaches in the treatment of COVID-19. While oral therapy is accepted as an effective and simple method, since the primary site of infection and disease progression of COVID-19 is mainly through the lungs, inhaled drug delivery directly to the lungs may be the most appropriate route of administration. To prevent or treat primary SARS-CoV-2 infections, it is essential to target the virus port of entry in the respiratory tract and airway epithelium, which requires rapid and high-intensity inhibition or control of viral entry or replication. To achieve success in this field, inhalation therapy is the most attractive treatment approach due to efficacy/safety profiles. In this review article, pulmonary drug delivery as a unique treatment option in lung diseases will be briefly reviewed. Then, possible inhalation therapies for the treatment of symptoms of COVID-19 will be discussed and the results of clinical trials will be presented. By pulmonary delivery of the currently approved drugs for COVID-19, efficacy of the treatment would be improved along with reducing systemic side effects.
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Affiliation(s)
- Shohreh Alipour
- Pharmaceutical Sciences Research Center and Department of Food & Drug Quality Control, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Laleh Mahmoudi
- Department of Clinical Pharmacy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Fatemeh Ahmadi
- Center for Nanotechnology in Drug Delivery and Department of Pharmaceutics, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
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Shafiee A, Athar MMT, Shahid A, Ghafoor MS, Ayyan M, Zahid A, Cheema HA. Curcumin for the treatment of COVID-19 patients: A meta-analysis of randomized controlled trials. Phytother Res 2023; 37:1167-1175. [PMID: 36640146 DOI: 10.1002/ptr.7724] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 12/19/2022] [Accepted: 12/29/2022] [Indexed: 01/15/2023]
Abstract
Curcumin is a low-cost and easily accessible therapeutic option for COVID-19 patients. We aimed to conduct a meta-analysis to assess the effect of curcumin on clinical outcomes in COVID-19 patients. Various databases, including PubMed, the Cochrane Library and Embase were searched from inception until October 2022 for randomized controlled trials (RCTs) evaluating curcumin use in COVID-19 patients. Results from 13 RCTs were pooled using R software version 4.1.0. Curcumin reduced the risk of all-cause mortality (RR 0.38; 95% CI: 0.20-0.72; moderate certainty of evidence), and patients with no recovery status (RR 0.54; 95% CI: 0.42-0.70; moderate certainty of evidence) but had no effect on the incidence of mechanical ventilation and hospitalization, and the rate of a positive viral PCR test. The results of subgroup analysis suggested a higher benefit with early administration of curcumin (within 5 days of onset of symptoms) and with the use of combination regimens. Curcumin is likely to be of benefit in mild-to-moderate COVID-19 patients, but large-scale RCTs are needed to confirm these findings. The limitations of our meta-analysis include the small sample sizes of the included RCTs and the variable formulations of curcumin used across the studies.
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Affiliation(s)
- Arman Shafiee
- Clinical Research Development Unit, Alborz University of Medical Sciences, Karaj, Iran.,Student Research Committee, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
| | | | - Abia Shahid
- Department of Medicine, King Edward Medical University, Lahore, Pakistan
| | | | - Muhammad Ayyan
- Department of Medicine, King Edward Medical University, Lahore, Pakistan
| | - Afra Zahid
- Department of Medicine, King Edward Medical University, Lahore, Pakistan
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Sharma H, Ilyas A, Chowdhury A, Poddar NK, Chaudhary AA, Shilbayeh SAR, Ibrahim AA, Khan S. Does COVID-19 lockdowns have impacted on global dengue burden? A special focus to India. BMC Public Health 2022; 22:1402. [PMID: 35869470 PMCID: PMC9304795 DOI: 10.1186/s12889-022-13720-w] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Accepted: 06/27/2022] [Indexed: 12/12/2022] Open
Abstract
Background The world has been battling several vector-borne diseases since time immemorial. Socio-economic marginality, precipitation variations and human behavioral attributes play a major role in the proliferation of these diseases. Lockdown and social distancing have affected social behavioral aspects of human life and somehow impact on the spread of vector borne diseases. This article sheds light into the relationship between COVID-19 lockdown and global dengue burden with special focus on India. It also focuses on the interconnection of the COVID-19 pandemic (waves 1 and 2) and the alteration of human behavioral patterns in dengue cases. Methods We performed a systematic search using various resources from different platforms and websites, such as Medline; Pubmed; PAHO; WHO; CDC; ECDC; Epidemiology Unit Ministry of Health (Sri Lanka Government); NASA; NVBDCP from 2015 until 2021. We have included many factors, such as different geographical conditions (tropical climate, semitropic and arid conditions); GDP rate (developed nations, developing nations, and underdeveloped nations). We also categorized our data in order to conform to COVID-19 duration from 2019 to 2021. Data was extracted for the complete duration of 10 years (2012 to 2021) from various countries with different geographical region (arid region, semitropic/semiarid region and tropical region). Results There was a noticeable reduction in dengue cases in underdeveloped (70–85%), developing (50–90%), and developed nations (75%) in the years 2019 and 2021. The dengue cases drastically reduced by 55–65% with the advent of COVID-19 s wave in the year 2021 across the globe. Conclusions At present, we can conclude that COVID-19 and dengue show an inverse relationship. These preliminary, data-based observations should guide clinical practice until more data are made public and basis for further medical research. • COVID-19 has increased the burden on the health care system across the globe. • COVID-19 has inverse relation with the occurrence of Dengue cases. • Dengue situation is worse in countries with low GDP. • Human behavior and social distancing have direct correlation with the number of Dengue cases. • Cross-reactivity or overlap between Dengue and COVID-19, has proportional effect on each other.
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Khorattanakulchai N, Srisutthisamphan K, Shanmugaraj B, Manopwisedjaroen S, Rattanapisit K, Panapitakkul C, Kemthong T, Suttisan N, Malaivijitnond S, Thitithanyanont A, Jongkaewwattana A, Phoolcharoen W. A recombinant subunit vaccine candidate produced in plants elicits neutralizing antibodies against SARS-CoV-2 variants in macaques. FRONTIERS IN PLANT SCIENCE 2022; 13:901978. [PMID: 36247553 PMCID: PMC9555276 DOI: 10.3389/fpls.2022.901978] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Accepted: 08/29/2022] [Indexed: 06/16/2023]
Abstract
Since the outbreak of the coronavirus disease (COVID) pandemic in 2019, the development of effective vaccines to combat the infection has been accelerated. With the recent emergence of highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC), there are concerns regarding the immune escape from vaccine-induced immunity. Hence an effective vaccine against VOC with a potent immune response is required. Our previous study confirmed that the two doses of the plant-produced receptor-binding domain (RBD) of SARS-CoV-2 fused with the Fc region of human IgG1, namely Baiya SARS-CoV-2 Vax 1, showed high immunogenicity in mice and monkeys. Here, we aimed to evaluate the immunogenicity of a three-dose intramuscular injection of Baiya SARS-CoV-2 Vax 1 on days 0, 21, and 133 in cynomolgus monkeys. At 14 days after immunization, blood samples were collected to determine RBD-specific antibody titer, neutralizing antibody, and pseudovirus neutralizing antibody titers. Immunized monkeys developed significantly high levels of antigen-specific antibodies against SARS-CoV-2 compared to the control group. Interestingly, the sera collected from immunized monkeys also showed a neutralizing antibody response against the SARS-CoV-2 VOCs; Alpha, Beta, Gamma, Delta, and Omicron. These findings demonstrate that a three-dose regimen of Baiya SARS-CoV-2 Vax 1 vaccine elicits neutralizing immune response against SARS-CoV-2 variants.
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Affiliation(s)
- Narach Khorattanakulchai
- Center of Excellence in Plant-produced Pharmaceuticals, Chulalongkorn University, Bangkok, Thailand
- Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
| | - Kanjana Srisutthisamphan
- Virology and Cell Technology Laboratory, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency, Pathum Thani, Thailand
| | | | | | | | - Chalisa Panapitakkul
- Center of Excellence in Plant-produced Pharmaceuticals, Chulalongkorn University, Bangkok, Thailand
- Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
| | - Taratorn Kemthong
- National Primate Research Center of Thailand-Chulalongkorn University, Saraburi, Thailand
| | - Nutchanat Suttisan
- National Primate Research Center of Thailand-Chulalongkorn University, Saraburi, Thailand
| | | | | | - Anan Jongkaewwattana
- Virology and Cell Technology Laboratory, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency, Pathum Thani, Thailand
| | - Waranyoo Phoolcharoen
- Center of Excellence in Plant-produced Pharmaceuticals, Chulalongkorn University, Bangkok, Thailand
- Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
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10
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Kumar S, Dutta D, Ravichandiran V, Sukla S. Monoclonal antibodies: a remedial approach to prevent SARS-CoV-2 infection. 3 Biotech 2022; 12:227. [PMID: 35982759 PMCID: PMC9383686 DOI: 10.1007/s13205-022-03281-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2022] [Accepted: 07/26/2022] [Indexed: 11/07/2022] Open
Abstract
SARS-CoV-2, the newly emerged virus of the Coronaviridae family is causing havoc worldwide. The novel coronavirus 2019 was first reported in Wuhan, China marked as the third highly infectious pathogenic virus of the twenty-first century. The typical manifestations of COVID-19 include cough, sore throat, fever, fatigue, loss of sense of taste and difficulties in breathing. Large numbers of SARS-CoV-2 infected patients have mild to moderate symptoms, however severe and life-threatening cases occur in about 5-10% of infections with an approximately 2% mortality rate. For the treatment of SARS-CoV-2, the use of neutralizing monoclonal antibodies (mAbs) could be one approach. The receptor binding domain (RBD) and N-terminal domain (NTD) situated on the peak of the spike protein (S-Protein) of SARS-CoV-2 are immunogenic in nature, therefore, can be targeted by neutralizing monoclonal antibodies. Several bioinformatics approaches highlight the identification of novel SARS-CoV-2 epitopes which can be targeted for the development of COVID-19 therapeutics. Here we present a summary of neutralizing mAbs isolated from COVID-19 infected patients which are anticipated to be a better therapeutic alternative against SARS-CoV-2. However, provided the vast escalation of the disease worldwide affecting people from all strata, affording expensive mAb therapy will not be feasible. Hence other strategies are also being employed to find suitable vaccine candidates and antivirals against SARS-CoV-2 that can be made easily available to the population.
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Affiliation(s)
- Sonu Kumar
- Department of Pharmacology and Toxicology, National Institute of Pharmaceuticals Education and Research, 168, Maniktala Main Road, Kolkata, 700054 West Bengal India
| | - Debrupa Dutta
- Department of Pharmacology and Toxicology, National Institute of Pharmaceuticals Education and Research, 168, Maniktala Main Road, Kolkata, 700054 West Bengal India
| | - Velayutham Ravichandiran
- Department of Natural Products, National Institute of Pharmaceuticals Education and Research, 168, Maniktala Main Road, Kolkata, 700054 West Bengal India
| | - Soumi Sukla
- Department of Pharmacology and Toxicology, National Institute of Pharmaceuticals Education and Research, 168, Maniktala Main Road, Kolkata, 700054 West Bengal India
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Li R, Shao G, Xie Z, Hu Z, Feng K, He J, Wang H, Fu J, Zhang X, Xie Q. Construction and Immunogenicity of a Recombinant Pseudorabies Virus Expressing SARS-CoV-2-S and SARS-CoV-2-N. Front Vet Sci 2022; 9:920087. [PMID: 35982925 PMCID: PMC9380597 DOI: 10.3389/fvets.2022.920087] [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: 04/14/2022] [Accepted: 06/22/2022] [Indexed: 12/05/2022] Open
Abstract
Coronavirus (CoV) is an important pathogen of humans and animals, which can infect humans or animals through the respiratory mucosal route. Syndrome coronavirus 2 (SARS-CoV-2) is quite similar to syndrome coronavirus (SARS-CoV) with the same receptor, angiotensin-converting enzyme 2 (ACE2). The S and N proteins are the most important protective antigens of the SARS-CoV-2. The S protein on the viral membrane mediates the virus attachment with the host cells, and the N protein is the most abundant expression during infection. In this study, the recombinant viruses expressing the S and N proteins of SARS-CoV-2 were successfully constructed by Red/ET recombinant technology using Pseudorabies virus (PRV) strain Bartha-K61 as a vector. Genetic stability and growth kinetics analysis showed that the recombinant viruses rPRV-SARS-CoV-2-S and rPRV-SARS-CoV-2-N had similar genetic stability and proliferation characteristics to the parental PRV. The immunoassay results showed that mice immunized with recombinant viruses could produce total IgG antibodies. Therefore, PRV is feasible and promising as a viral vector to express SARS-CoV-2-S and SARS-CoV-2-N genes. This study can provide a reference for future research on live vector vaccines for domestic animals, pets, and wild animals.
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Affiliation(s)
- Ruoying Li
- Heyuan Branch, Guangdong Provincial Laboratory of Lingnan Modern Agricultural Science and Technology & Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, China
- Guangdong Engineering Research Center for Vector Vaccine of Animal Virus, College of Animal Science, South China Agricultural University, Guangzhou, China
- South China Collaborative Innovation Center for Poultry Disease Control and Product Safety, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Guanming Shao
- Heyuan Branch, Guangdong Provincial Laboratory of Lingnan Modern Agricultural Science and Technology & Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, China
- Guangdong Engineering Research Center for Vector Vaccine of Animal Virus, College of Animal Science, South China Agricultural University, Guangzhou, China
- South China Collaborative Innovation Center for Poultry Disease Control and Product Safety, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Zi Xie
- Heyuan Branch, Guangdong Provincial Laboratory of Lingnan Modern Agricultural Science and Technology & Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, China
- Guangdong Engineering Research Center for Vector Vaccine of Animal Virus, College of Animal Science, South China Agricultural University, Guangzhou, China
- South China Collaborative Innovation Center for Poultry Disease Control and Product Safety, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Zezhong Hu
- Heyuan Branch, Guangdong Provincial Laboratory of Lingnan Modern Agricultural Science and Technology & Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, China
- Guangdong Engineering Research Center for Vector Vaccine of Animal Virus, College of Animal Science, South China Agricultural University, Guangzhou, China
- South China Collaborative Innovation Center for Poultry Disease Control and Product Safety, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Keyu Feng
- Heyuan Branch, Guangdong Provincial Laboratory of Lingnan Modern Agricultural Science and Technology & Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, China
- Guangdong Engineering Research Center for Vector Vaccine of Animal Virus, College of Animal Science, South China Agricultural University, Guangzhou, China
- South China Collaborative Innovation Center for Poultry Disease Control and Product Safety, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Jiahui He
- Heyuan Branch, Guangdong Provincial Laboratory of Lingnan Modern Agricultural Science and Technology & Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, China
- Guangdong Engineering Research Center for Vector Vaccine of Animal Virus, College of Animal Science, South China Agricultural University, Guangzhou, China
- South China Collaborative Innovation Center for Poultry Disease Control and Product Safety, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Hailong Wang
- State Key Laboratory of Microbial Technology, Institute of Microbial Technology, Helmholtz International Lab for Anti-infectives, Shandong University–Helmholtz Institute of Biotechnology, Shandong University, Jinan, China
| | - Jun Fu
- State Key Laboratory of Microbial Technology, Institute of Microbial Technology, Helmholtz International Lab for Anti-infectives, Shandong University–Helmholtz Institute of Biotechnology, Shandong University, Jinan, China
| | - Xinheng Zhang
- Heyuan Branch, Guangdong Provincial Laboratory of Lingnan Modern Agricultural Science and Technology & Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, China
- Guangdong Engineering Research Center for Vector Vaccine of Animal Virus, College of Animal Science, South China Agricultural University, Guangzhou, China
- South China Collaborative Innovation Center for Poultry Disease Control and Product Safety, College of Animal Science, South China Agricultural University, Guangzhou, China
- Key Laboratory of Animal Health Aquaculture and Environmental Control, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Qingmei Xie
- Heyuan Branch, Guangdong Provincial Laboratory of Lingnan Modern Agricultural Science and Technology & Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, China
- Guangdong Engineering Research Center for Vector Vaccine of Animal Virus, College of Animal Science, South China Agricultural University, Guangzhou, China
- South China Collaborative Innovation Center for Poultry Disease Control and Product Safety, College of Animal Science, South China Agricultural University, Guangzhou, China
- Key Laboratory of Animal Health Aquaculture and Environmental Control, College of Animal Science, South China Agricultural University, Guangzhou, China
- *Correspondence: Qingmei Xie
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12
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Pan X, Kaminga AC, Chen Y, Liu H, Wen SW, Fang Y, Jia P, Liu A. Auxiliary Screening COVID-19 by Serology. Front Public Health 2022; 10:819841. [PMID: 35983367 PMCID: PMC9380738 DOI: 10.3389/fpubh.2022.819841] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Accepted: 06/21/2022] [Indexed: 11/13/2022] Open
Abstract
Background The 2019 novel coronavirus (COVID-19) pandemic remains rampant in many countries/regions. Improving the positive detection rate of COVID-19 infection is an important measure for control and prevention of this pandemic. This meta-analysis aims to systematically summarize the current characteristics of the auxiliary screening methods by serology for COVID-19 infection in real world. Methods Web of Science, Cochrane Library, Embase, PubMed, CNKI, and Wangfang databases were searched for relevant articles published prior to May 1st, 2022. Data on specificity, sensitivity, positive/negative likelihood ratio, area under curve (AUC), and diagnostic odds ratio (dOR) were calculated purposefully. Results Sixty-two studies were included with 35,775 participants in the meta-analysis. Among these studies, the pooled estimates for area under the summary receiver operator characteristic of IgG and IgM to predicting COVID-19 diagnosis were 0.974 and 0.928, respectively. The IgG dOR was 209.78 (95% CI: 106.12 to 414.67). The IgM dOR was 78.17 (95% CI: 36.76 to 166.25). Conclusion Our findings support serum-specific antibody detection may be the main auxiliary screening methods for COVID-19 infection in real world.
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Affiliation(s)
- Xiongfeng Pan
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China
| | - Atipatsa C. Kaminga
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China
- Department of Mathematics and Statistics, Mzuzu University, Mzuzu, Malawi
| | - Yuyao Chen
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China
| | - Hongying Liu
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China
| | - Shi Wu Wen
- OMNI Research Group, Ottawa Hospital Research Institute, Ottawa, ON, Canada
- Department of Obstetrics and Gynaecology, University of Ottawa Faculty of Medicine, Ottawa, ON, Canada
- School of Epidemiology and Public Health, University of Ottawa Faculty of Medicine, Ottawa, ON, Canada
| | - Yingjing Fang
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China
| | - Peng Jia
- School of Resource and Environmental Sciences, Wuhan University, Wuhan, China
- International Institute of Spatial Lifecourse Health (ISLE), Wuhan University, Wuhan, China
- *Correspondence: Peng Jia
| | - Aizhong Liu
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China
- Aizhong Liu
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13
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Copana Olmos R, Guillen Rocha N, Mamani Y, Rodriguez Alvarez G, Ovando Campos A, Camacho Tufiño C. Hybrid Immunity for COVID-19 in Bolivian Healthcare Workers. Cureus 2022; 14:e27449. [PMID: 36051711 PMCID: PMC9420450 DOI: 10.7759/cureus.27449] [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] [Accepted: 07/26/2022] [Indexed: 11/29/2022] Open
Abstract
Introduction Vaccination is one of the pillars for the prevention of COVID-19 in healthcare workers (HCWs). The present study aims to determine the effectiveness of vaccination for COVID-19 as well as hybrid immunity in previously infected HCWs in a hospital in a developing country. Methods An observational study was carried out on health personnel with a complete COVID-19 vaccination schedule according to their previous infection status, with a follow-up period of 15 months. Results In this study, 335 subjects were enrolled, of which 32.8% had a previous infection with COVID-19. The safety of vaccines was determined by estimating the presence of adverse effects of vaccination and immunization (AEVI), with the first and second doses showing an incidence of 8.2% and 9.5% respectively, during the second and third waves. Around 5.7% of immunized personnel were sick and 8.4% in the fourth wave; the serum value of neutralizing antibodies was normal at 60.2% with no differences between vaccines (p=0.164). However, in personnel with hybrid immunity, there were normal levels of antibodies in 81.8% of cases (p= 0.023), fewer days of medical leave (6.4 days (standard deviation=1.4) (p=0.067)), higher immunoglobin values (p=0.011) and an insignificantly (p=0.248) lower rate of COVID-19 presentation. Conclusion Vaccination, when applied to people who previously acquired natural immunity, generates a hybrid immunity that is robust, and could have a longer duration, as well as greater efficacy for new COVID-19 variants of concern.
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14
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Zeng S, Li Y, Zhu W, Luo Z, Wu K, Li X, Fang Y, Qin Y, Chen W, Li Z, Zou L, Liu X, Yi L, Fan S. The Advances of Broad-Spectrum and Hot Anti-Coronavirus Drugs. Microorganisms 2022; 10:microorganisms10071294. [PMID: 35889013 PMCID: PMC9317368 DOI: 10.3390/microorganisms10071294] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 06/22/2022] [Accepted: 06/24/2022] [Indexed: 02/01/2023] Open
Abstract
Coronaviruses, mainly including severe acute respiratory syndrome virus, severe acute respiratory syndrome coronavirus 2, Middle East respiratory syndrome virus, human coronavirus OC43, chicken infectious bronchitis virus, porcine infectious gastroenteritis virus, porcine epidemic diarrhea virus, and murine hepatitis virus, can cause severe diseases in humans and livestock. The severe acute respiratory syndrome coronavirus 2 is infecting millions of human beings with high morbidity and mortality worldwide, and the multiplicity of swine epidemic diarrhea coronavirus in swine suggests that coronaviruses seriously jeopardize the safety of public health and that therapeutic intervention is urgently needed. Currently, the most effective methods of prevention and control for coronaviruses are vaccine immunization and pharmacotherapy. However, the emergence of mutated viruses reduces the effectiveness of vaccines. In addition, vaccine developments often lag behind, making it difficult to put them into use early in the outbreak. Therefore, it is meaningful to screen safe, cheap, and broad-spectrum antiviral agents for coronaviruses. This review systematically summarizes the mechanisms and state of anti-human and porcine coronavirus drugs, in order to provide theoretical support for the development of anti-coronavirus drugs and other antivirals.
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Affiliation(s)
- Sen Zeng
- College of Veterinary Medicine, South China Agricultural University, No. 483 Wushan Road, Tianhe District, Guangzhou 510642, China; (S.Z.); (Y.L.); (W.Z.); (Z.L.); (K.W.); (X.L.); (Y.F.); (Y.Q.); (W.C.); (Z.L.); (L.Z.); (X.L.)
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, China
| | - Yuwan Li
- College of Veterinary Medicine, South China Agricultural University, No. 483 Wushan Road, Tianhe District, Guangzhou 510642, China; (S.Z.); (Y.L.); (W.Z.); (Z.L.); (K.W.); (X.L.); (Y.F.); (Y.Q.); (W.C.); (Z.L.); (L.Z.); (X.L.)
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, China
| | - Wenhui Zhu
- College of Veterinary Medicine, South China Agricultural University, No. 483 Wushan Road, Tianhe District, Guangzhou 510642, China; (S.Z.); (Y.L.); (W.Z.); (Z.L.); (K.W.); (X.L.); (Y.F.); (Y.Q.); (W.C.); (Z.L.); (L.Z.); (X.L.)
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, China
| | - Zipeng Luo
- College of Veterinary Medicine, South China Agricultural University, No. 483 Wushan Road, Tianhe District, Guangzhou 510642, China; (S.Z.); (Y.L.); (W.Z.); (Z.L.); (K.W.); (X.L.); (Y.F.); (Y.Q.); (W.C.); (Z.L.); (L.Z.); (X.L.)
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, China
| | - Keke Wu
- College of Veterinary Medicine, South China Agricultural University, No. 483 Wushan Road, Tianhe District, Guangzhou 510642, China; (S.Z.); (Y.L.); (W.Z.); (Z.L.); (K.W.); (X.L.); (Y.F.); (Y.Q.); (W.C.); (Z.L.); (L.Z.); (X.L.)
- Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou 510642, China
| | - Xiaowen Li
- College of Veterinary Medicine, South China Agricultural University, No. 483 Wushan Road, Tianhe District, Guangzhou 510642, China; (S.Z.); (Y.L.); (W.Z.); (Z.L.); (K.W.); (X.L.); (Y.F.); (Y.Q.); (W.C.); (Z.L.); (L.Z.); (X.L.)
- Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou 510642, China
| | - Yiqi Fang
- College of Veterinary Medicine, South China Agricultural University, No. 483 Wushan Road, Tianhe District, Guangzhou 510642, China; (S.Z.); (Y.L.); (W.Z.); (Z.L.); (K.W.); (X.L.); (Y.F.); (Y.Q.); (W.C.); (Z.L.); (L.Z.); (X.L.)
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, China
| | - Yuwei Qin
- College of Veterinary Medicine, South China Agricultural University, No. 483 Wushan Road, Tianhe District, Guangzhou 510642, China; (S.Z.); (Y.L.); (W.Z.); (Z.L.); (K.W.); (X.L.); (Y.F.); (Y.Q.); (W.C.); (Z.L.); (L.Z.); (X.L.)
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, China
| | - Wenxian Chen
- College of Veterinary Medicine, South China Agricultural University, No. 483 Wushan Road, Tianhe District, Guangzhou 510642, China; (S.Z.); (Y.L.); (W.Z.); (Z.L.); (K.W.); (X.L.); (Y.F.); (Y.Q.); (W.C.); (Z.L.); (L.Z.); (X.L.)
- Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou 510642, China
| | - Zhaoyao Li
- College of Veterinary Medicine, South China Agricultural University, No. 483 Wushan Road, Tianhe District, Guangzhou 510642, China; (S.Z.); (Y.L.); (W.Z.); (Z.L.); (K.W.); (X.L.); (Y.F.); (Y.Q.); (W.C.); (Z.L.); (L.Z.); (X.L.)
- Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou 510642, China
| | - Linke Zou
- College of Veterinary Medicine, South China Agricultural University, No. 483 Wushan Road, Tianhe District, Guangzhou 510642, China; (S.Z.); (Y.L.); (W.Z.); (Z.L.); (K.W.); (X.L.); (Y.F.); (Y.Q.); (W.C.); (Z.L.); (L.Z.); (X.L.)
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, China
| | - Xiaodi Liu
- College of Veterinary Medicine, South China Agricultural University, No. 483 Wushan Road, Tianhe District, Guangzhou 510642, China; (S.Z.); (Y.L.); (W.Z.); (Z.L.); (K.W.); (X.L.); (Y.F.); (Y.Q.); (W.C.); (Z.L.); (L.Z.); (X.L.)
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, China
| | - Lin Yi
- College of Veterinary Medicine, South China Agricultural University, No. 483 Wushan Road, Tianhe District, Guangzhou 510642, China; (S.Z.); (Y.L.); (W.Z.); (Z.L.); (K.W.); (X.L.); (Y.F.); (Y.Q.); (W.C.); (Z.L.); (L.Z.); (X.L.)
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, China
- Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou 510642, China
- Correspondence: (L.Y.); (S.F.); Fax: +86-20-8528-0245 (S.F.)
| | - Shuangqi Fan
- College of Veterinary Medicine, South China Agricultural University, No. 483 Wushan Road, Tianhe District, Guangzhou 510642, China; (S.Z.); (Y.L.); (W.Z.); (Z.L.); (K.W.); (X.L.); (Y.F.); (Y.Q.); (W.C.); (Z.L.); (L.Z.); (X.L.)
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, China
- Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou 510642, China
- Correspondence: (L.Y.); (S.F.); Fax: +86-20-8528-0245 (S.F.)
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Paidas MJ, Sampath N, Schindler EA, Cosio DS, Ndubizu CO, Shamaladevi N, Kwal J, Rodriguez S, Ahmad A, Kenyon NS, Jayakumar AR. Mechanism of Multi-Organ Injury in Experimental COVID-19 and Its Inhibition by a Small Molecule Peptide. Front Pharmacol 2022; 13:864798. [PMID: 35712703 PMCID: PMC9196045 DOI: 10.3389/fphar.2022.864798] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Accepted: 04/20/2022] [Indexed: 12/11/2022] Open
Abstract
Severe disease from SARS-CoV-2 infection often progresses to multi-organ failure and results in an increased mortality rate amongst these patients. However, underlying mechanisms of SARS- CoV-2-induced multi-organ failure and subsequent death are still largely unknown. Cytokine storm, increased levels of inflammatory mediators, endothelial dysfunction, coagulation abnormalities, and infiltration of inflammatory cells into the organs contribute to the pathogenesis of COVID-19. One potential consequence of immune/inflammatory events is the acute progression of generalized edema, which may lead to death. We, therefore, examined the involvement of water channels in the development of edema in multiple organs and their contribution to organ dysfunction in a Murine Hepatitis Virus-1 (MHV-1) mouse model of COVID-19. Using this model, we recently reported multi-organ pathological abnormalities and animal death similar to that reported in humans with SARS-CoV-2 infection. We now identified an alteration in protein levels of AQPs 1, 4, 5, and 8 and associated oxidative stress, along with various degrees of tissue edema in multiple organs, which correlate well with animal survival post-MHV-1 infection. Furthermore, our newly created drug (a 15 amino acid synthetic peptide, known as SPIKENET) that was designed to prevent the binding of spike glycoproteins with their receptor(s), angiotensin- converting enzyme 2 (ACE2), and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) (SARS-CoV-2 and MHV-1, respectively), ameliorated animal death and reversed altered levels of AQPs and oxidative stress post-MHV-1 infection. Collectively, our findings suggest the possible involvement of altered aquaporins and the subsequent edema, likely mediated by the virus-induced inflammatory and oxidative stress response, in the pathogenesis of COVID- 19 and the potential of SPIKENET as a therapeutic option.
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Affiliation(s)
- Michael J. Paidas
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of Miami Miller School of Medicine, Miami, FL, United States
- *Correspondence: Michael J. Paidas, ; Arumugam R. Jayakumar,
| | - Natarajan Sampath
- School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, India
| | - Emma A. Schindler
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of Miami Miller School of Medicine, Miami, FL, United States
| | - Daniela S. Cosio
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of Miami Miller School of Medicine, Miami, FL, United States
| | - Chima Obianuju Ndubizu
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of Miami Miller School of Medicine, Miami, FL, United States
| | | | - Jaclyn Kwal
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of Miami Miller School of Medicine, Miami, FL, United States
| | - Suset Rodriguez
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of Miami Miller School of Medicine, Miami, FL, United States
| | - Anis Ahmad
- Department of Radiation Oncology, Sylvester Cancer Center, University of Miami School of Medicine, Miami, FL, United States
| | - Norma Sue Kenyon
- Microbiology & Immunology and Biomedical Engineering, Diabetes Research Institute, University of Miami, Miami, FL, United States
| | - Arumugam R. Jayakumar
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of Miami Miller School of Medicine, Miami, FL, United States
- *Correspondence: Michael J. Paidas, ; Arumugam R. Jayakumar,
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16
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Wang LG, Wang L. Current Strategies in Treating Cytokine Release Syndrome Triggered by Coronavirus SARS-CoV-2. Immunotargets Ther 2022; 11:23-35. [PMID: 35611161 PMCID: PMC9124488 DOI: 10.2147/itt.s360151] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Accepted: 05/07/2022] [Indexed: 12/15/2022] Open
Abstract
Since the beginning of the SARS-CoV-2 pandemic, the treatments and management of the deadly COVID-19 disease have made great progress. The strategies for developing novel treatments against COVID-19 include antiviral small molecule drugs, cell and gene therapies, immunomodulators, neutralizing antibodies, and combination therapies. Among them, immunomodulators are the most studied treatments. The small molecule antiviral drugs and immunoregulators are expected to be effective against viral variants of SARS-CoV-2 as these drugs target either conservative parts of the virus or common pathways of inflammation. Although the immunoregulators have shown benefits in reducing mortality of cytokine release syndrome (CRS) triggered by SARS-CoV-2 infections, extensive investigations on this class of treatment to launch novel therapies that substantially improve efficacy and reduce side effects are still warranted. Moreover, great challenges have emerged as the SARS-CoV-2 virus quickly, frequently, and continuously evolved. This review provides an update and summarizes the recent advances in the treatment of COVID-19 and in particular emphasized the strategies in managing CRS triggered by SARS-CoV-2. A brief perspective in the battle against the deadly disease was also provided.
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Affiliation(s)
- Long G Wang
- Department of Research and Development, Natrogen Therapeutics International, Inc., Valhalla, NY, USA
| | - Luxi Wang
- Department of Clinical Research, Clinipace Clinical Research, Morrisville, NC, USA
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17
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Kianpour M, Akbarian M, Uversky VN. Nanoparticles for Coronavirus Control. NANOMATERIALS (BASEL, SWITZERLAND) 2022; 12:1602. [PMID: 35564311 PMCID: PMC9104235 DOI: 10.3390/nano12091602] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 05/06/2022] [Accepted: 05/06/2022] [Indexed: 01/18/2023]
Abstract
More than 2 years have passed since the SARS-CoV-2 outbreak began, and many challenges that existed at the beginning of this pandemic have been solved. Some countries have been able to overcome this global challenge by relying on vaccines against the virus, and vaccination has begun in many countries. Many of the proposed vaccines have nanoparticles as carriers, and there are different nano-based diagnostic approaches for rapid detection of the virus. In this review article, we briefly examine the biology of SARS-CoV-2, including the structure of the virus and what makes it pathogenic, as well as describe biotechnological methods of vaccine production, and types of the available and published nano-based ideas for overcoming the virus pandemic. Among these issues, various physical and chemical properties of nanoparticles are discussed to evaluate the optimal conditions for the production of the nano-mediated vaccines. At the end, challenges facing the international community and biotechnological answers for future viral attacks are reviewed.
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Affiliation(s)
- Maryam Kianpour
- Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan;
| | - Mohsen Akbarian
- Department of Chemistry, National Cheng Kung University, Tainan 701, Taiwan
| | - Vladimir N. Uversky
- Department of Molecular Medicine and Health Byrd Alzheimer’s Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA
- Laboratory of New Methods in Biology, Institute for Biological Instrumentation of the Russian Academy of Sciences, Federal Research Center ‘‘Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences’’, 142290 Pushchino, Moscow Region, Russia
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18
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Liu T, Xu J, Guo Q, Zhang D, Li J, Qian W, Guo H, Zhou X, Hou S. Identification, Efficacy, and Stability Evaluation of Succinimide Modification With a High Abundance in the Framework Region of Golimumab. Front Chem 2022; 10:826923. [PMID: 35449588 PMCID: PMC9017650 DOI: 10.3389/fchem.2022.826923] [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: 12/02/2021] [Accepted: 03/08/2022] [Indexed: 11/24/2022] Open
Abstract
Succinimide (Asu) is the intermediate for asparagine deamidation in therapeutic proteins, and it can be readily hydrolyzed to form aspartate and iso-aspartate residues. Moreover, Asu plays an important role in the protein degradation pathways, asparagine deamidation, and aspartic acid isomerization. Here, Asu modification with a high abundance in the framework region (FR) of golimumab was first reported, the effect of denaturing buffer pH on the Asu modification homeostasis was studied, and the results revealed that it was relatively stable over a pH range of 6.0–7.0 whereas a rapid decrease at pH 8.0. Then, the peptide-based multi-attribute method (MAM) analyses showed that the Asu formation was at Asn 43 in the FR of the heavy chain. Meanwhile, the efficacy [affinity, binding and bioactivity, complement-dependent cytotoxicity (CDC) activity, and antibody-dependent cell-mediated cytotoxicity (ADCC) activity] and stability of the Asu modification of golimumab were evaluated, and the current results demonstrated comparable efficacy and stability between the Asu low- and high-abundance groups. Our findings provide valuable insights into Asu modification and its effect on efficacy and stability, and this study also demonstrates that there is a need to develop a broad-spectrum, rapid, and accurate platform to identify and characterize new peaks in the development of therapeutic proteins, particularly for antibody drugs.
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Affiliation(s)
- Tao Liu
- Department of Oncology, Huashan Hospital, Fudan University, Shanghai, China
- State Key Laboratory of Antibody Medicine and Targeted Therapy, Shanghai, China
- NMPA Key Laboratory for Quality Control of Therapeutic Monoclonal Antibodies, Shanghai, China
| | - Jin Xu
- State Key Laboratory of Antibody Medicine and Targeted Therapy, Shanghai, China
- NMPA Key Laboratory for Quality Control of Therapeutic Monoclonal Antibodies, Shanghai, China
- School of Pharmaceutical Sciences, Liaocheng University, Liaocheng, China
- Shanghai Zhangjiang Biotechnology Co., Ltd., Shanghai, China
| | - Qingcheng Guo
- Taizhou Mabtech Pharmaceuticals Co., Ltd., Taizhou, China
| | - Dapeng Zhang
- State Key Laboratory of Antibody Medicine and Targeted Therapy, Shanghai, China
- NMPA Key Laboratory for Quality Control of Therapeutic Monoclonal Antibodies, Shanghai, China
- School of Pharmaceutical Sciences, Liaocheng University, Liaocheng, China
| | - Jun Li
- School of Pharmaceutical Sciences, Liaocheng University, Liaocheng, China
| | - Weizhu Qian
- State Key Laboratory of Antibody Medicine and Targeted Therapy, Shanghai, China
- NMPA Key Laboratory for Quality Control of Therapeutic Monoclonal Antibodies, Shanghai, China
- School of Pharmaceutical Sciences, Liaocheng University, Liaocheng, China
| | - Huaizu Guo
- State Key Laboratory of Antibody Medicine and Targeted Therapy, Shanghai, China
- NMPA Key Laboratory for Quality Control of Therapeutic Monoclonal Antibodies, Shanghai, China
- School of Pharmaceutical Sciences, Liaocheng University, Liaocheng, China
- Shanghai Zhangjiang Biotechnology Co., Ltd., Shanghai, China
- *Correspondence: Huaizu Guo, ; Xinli Zhou, ; Sheng Hou,
| | - Xinli Zhou
- Department of Oncology, Huashan Hospital, Fudan University, Shanghai, China
- *Correspondence: Huaizu Guo, ; Xinli Zhou, ; Sheng Hou,
| | - Sheng Hou
- State Key Laboratory of Antibody Medicine and Targeted Therapy, Shanghai, China
- NMPA Key Laboratory for Quality Control of Therapeutic Monoclonal Antibodies, Shanghai, China
- School of Pharmaceutical Sciences, Liaocheng University, Liaocheng, China
- *Correspondence: Huaizu Guo, ; Xinli Zhou, ; Sheng Hou,
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Entesari M, Zamani M, Heidarizadeh M, Moradi R, Khakdan F, Rafiei F. An Insight Into Detection Pathways/Biosensors of Highly Infectious Coronaviruses. Mol Biotechnol 2022; 64:339-354. [PMID: 34655396 PMCID: PMC8520350 DOI: 10.1007/s12033-021-00417-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Accepted: 10/07/2021] [Indexed: 01/12/2023]
Abstract
The outbreak of COVID-19 pandemic and its consequences have inflicted a substantial damage on the world. In this study, it was attempted to review the recent coronaviruses appeared among the human being and their epidemic/pandemic spread throughout the world. Currently, there is an inevitable need for the establishment of a quick and easily available biosensor for tracing COVID-19 in all countries. It has been known that the incubation time of COVID-19 lasts about 14 days and 25% of the infected individuals are asymptomatic. To improve the ability to determine SARS-CoV-2 precisely and reduce the risk of eliciting false-negative results produced by mutating nature of coronaviruses, many researchers have established a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay using mismatch-tolerant molecular beacons as multiplex real-time RT-PCR to distinguish between pathogenic and non-pathogenic strains of coronaviruses. The possible mechanisms and pathways for the detection of coronaviruses by biosensors have been reviewed in this study.
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Affiliation(s)
- Mehrnaz Entesari
- Department of Genetic Engineering and Molecular Genetics, Zanjan University, Zanjan, Iran
| | - Mina Zamani
- Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Mohammad Heidarizadeh
- Department of Biotechnology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran
| | - Rasoul Moradi
- Department of Chemical Engineering, School of Engineering & Applied Science, Khazar University, Baku, Azerbaijan
| | | | - Fariba Rafiei
- Department of Agronomy & Plant Breeding, Collage of Agriculture & Natural Resources, University of Tehran, Karaj, Iran
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20
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Cicchitto G, Cardillo L, de Martinis C, Sabatini P, Marchitiello R, Abate G, Rovetti A, Cavallera A, Apuzzo C, Ferrigno F, Fusco G. Effects of Casirivimab/Imdevimab Monoclonal Antibody Treatment among Vaccinated Patients Infected by SARS-CoV-2 Delta Variant. Viruses 2022; 14:v14030650. [PMID: 35337057 PMCID: PMC8950724 DOI: 10.3390/v14030650] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Revised: 03/15/2022] [Accepted: 03/19/2022] [Indexed: 02/04/2023] Open
Abstract
There is a growing interest in using monoclonal antibodies (mAbs) in the early stages of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection to prevent disease progression. Little is known about the efficacy of mAbs against the delta variant of concern and its clinical presentations. We evaluated the effect of casirivimab/imdevimab treatment among five delta vaccine breakthrough patients. Symptomatic non-hospitalized vaccinated patients were submitted to nasopharyngeal swabs for the detection of SARS-CoV-2 and Next-Generation Sequencing (NGS). Blood analysis and chest Computed Tomography were also performed. A cocktail of casirivimab/imdevimab was administrated, and patients were monitored weekly. Clinical evolution was evaluated by the regression of the symptoms, negative results by real-time RT-PCR, and by the need of hospitalization: these aspects were considered as significant outcomes. In four cases, symptom reversion and viral load reduction were observed within 2 days and 7 days after mAbs treatment, respectively. Only one case, suffering from thymoma, was hospitalized 2 days later because of respiratory failure, which reverted within 18 days. mAbs treatment seems to be safe and effective against the delta variant and its clinical manifestations.
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Affiliation(s)
- Gaetano Cicchitto
- Department of Pneumology, COVID-19 Hospital “M. Scarlato”, 84018 Scafati, Salerno, Italy; (G.C.); (F.F.)
| | - Lorena Cardillo
- Istituto Zooprofilattico Sperimentale del Mezzogiorno, 80055 Portici, Naples, Italy; (C.d.M.); (G.F.)
- Correspondence: ; Tel.: +39-0817865509
| | - Claudio de Martinis
- Istituto Zooprofilattico Sperimentale del Mezzogiorno, 80055 Portici, Naples, Italy; (C.d.M.); (G.F.)
| | - Paola Sabatini
- Unit of Virology and Microbiology, “Umberto I” Hospital, 84014 Nocera Inferiore, Salerno, Italy;
| | - Rosita Marchitiello
- Unit of Clinical Pathology Laboratory, COVID-19 Hospital “M. Scarlato”, 84018 Scafati, Salerno, Italy; (R.M.); (G.A.); (A.R.)
| | - Giovanna Abate
- Unit of Clinical Pathology Laboratory, COVID-19 Hospital “M. Scarlato”, 84018 Scafati, Salerno, Italy; (R.M.); (G.A.); (A.R.)
| | - Adele Rovetti
- Unit of Clinical Pathology Laboratory, COVID-19 Hospital “M. Scarlato”, 84018 Scafati, Salerno, Italy; (R.M.); (G.A.); (A.R.)
| | - Antonietta Cavallera
- Department of Radiology, COVID-19 Hospital “M. Scarlato”, 84018 Scafati, Salerno, Italy; (A.C.); (C.A.)
| | - Camillo Apuzzo
- Department of Radiology, COVID-19 Hospital “M. Scarlato”, 84018 Scafati, Salerno, Italy; (A.C.); (C.A.)
| | - Francesco Ferrigno
- Department of Pneumology, COVID-19 Hospital “M. Scarlato”, 84018 Scafati, Salerno, Italy; (G.C.); (F.F.)
| | - Giovanna Fusco
- Istituto Zooprofilattico Sperimentale del Mezzogiorno, 80055 Portici, Naples, Italy; (C.d.M.); (G.F.)
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21
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Li YR, Dunn ZS, Garcia G, Carmona C, Zhou Y, Lee D, Yu J, Huang J, Kim JT, Arumugaswami V, Wang P, Yang L. Development of off-the-shelf hematopoietic stem cell-engineered invariant natural killer T cells for COVID-19 therapeutic intervention. Stem Cell Res Ther 2022; 13:112. [PMID: 35313965 PMCID: PMC8935266 DOI: 10.1186/s13287-022-02787-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Accepted: 10/16/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND New COVID-19 treatments are desperately needed as case numbers continue to rise and emergent strains threaten vaccine efficacy. Cell therapy has revolutionized cancer treatment and holds much promise in combatting infectious disease, including COVID-19. Invariant natural killer T (iNKT) cells are a rare subset of T cells with potent antiviral and immunoregulatory functions and an excellent safety profile. Current iNKT cell strategies are hindered by the extremely low presence of iNKT cells, and we have developed a platform to overcome this critical limitation. METHODS We produced allogeneic HSC-engineered iNKT (AlloHSC-iNKT) cells through TCR engineering of human cord blood CD34+ hematopoietic stem cells (HSCs) and differentiation of these HSCs into iNKT cells in an Ex Vivo HSC-Derived iNKT Cell Culture. We then established in vitro SARS-CoV-2 infection assays to assess AlloHSC-iNKT cell antiviral and anti-hyperinflammation functions. Lastly, using in vitro and in vivo preclinical models, we evaluated AlloHSC-iNKT cell safety and immunogenicity for off-the-shelf application. RESULTS We reliably generated AlloHSC-iNKT cells at high-yield and of high-purity; these resulting cells closely resembled endogenous human iNKT cells in phenotypes and functionalities. In cell culture, AlloHSC-iNKT cells directly killed SARS-CoV-2 infected cells and also selectively eliminated SARS-CoV-2 infection-stimulated inflammatory monocytes. In an in vitro mixed lymphocyte reaction (MLR) assay and an NSG mouse xenograft model, AlloHSC-iNKT cells were resistant to T cell-mediated alloreaction and did not cause GvHD. CONCLUSIONS Here, we report a method to robustly produce therapeutic levels of AlloHSC-iNKT cells. Preclinical studies showed that these AlloHSC-iNKT cells closely resembled endogenous human iNKT cells, could reduce SARS-CoV-2 virus infection load and mitigate virus infection-induced hyperinflammation, and meanwhile were free of GvHD-risk and resistant to T cell-mediated allorejection. These results support the development of AlloHSC-iNKT cells as a promising off-the-shelf cell product for treating COVID-19; such a cell product has the potential to target the new emerging SARS-CoV-2 variants as well as the future new emerging viruses.
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Affiliation(s)
- Yan-Ruide Li
- Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, 90095, USA
| | - Zachary Spencer Dunn
- Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, Los Angeles, CA, 90089, USA
| | - Gustavo Garcia
- Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, 90095, USA
| | - Camille Carmona
- Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, 90095, USA
| | - Yang Zhou
- Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, 90095, USA
| | - Derek Lee
- Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, 90095, USA
| | - Jiaji Yu
- Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, 90095, USA
| | - Jie Huang
- Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, 90095, USA
| | - Jocelyn T Kim
- Division of Infectious Diseases, Department of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA
| | - Vaithilingaraja Arumugaswami
- Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, 90095, USA
- Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, 90095, USA
| | - Pin Wang
- Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, Los Angeles, CA, 90089, USA
| | - Lili Yang
- Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
- Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
- Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
- Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
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22
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Pereira AA, de Oliveira Andrade A, de Andrade Palis A, Cabral AM, Barreto CGL, de Souza DB, de Paula Silva F, Santos FP, Silva GL, Guimarães JFV, de Araújo LAS, Nóbrega LR, Mendes LC, Brandão MR, Milagre ST, de Lima Gonçalves V, de Freitas Morales VH, da Conceição Lima V. Non-pharmacological treatments for COVID-19: current status and consensus. RESEARCH ON BIOMEDICAL ENGINEERING 2022. [PMCID: PMC7809889 DOI: 10.1007/s42600-020-00116-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Purpose COVID-19 is a disease caused by SARS-CoV-2 (coronavirus type 2 of the severe acute respiratory syndrome), isolated in China, in December 2019. The strategy currently used by physicians is to control disease and to treat symptoms, including non-pharmacological treatments, as there is still no specific treatment for COVID-19. Thus, the aim of this article is to carry out a systematic review about non-pharmacological treatments used for COVID-19, addressing current status and consensus found in the literature. Methods Three databases were consulted for evidence referring to the drugs indicated for COVID-19 (Cochrane Central, MEDLINE and Embase). The following terms and combinations were used: ((“2019-nCoV” OR 2019nCoV OR nCoV2019 OR “nCoV-2019” OR “COVID-19” OR COVID19 OR “HCoV-19” OR HCoV19 OR CoV OR “2019 novel*” OR Ncov OR “n-cov” OR “SARS-CoV-2” OR “SARSCoV-2” OR “SARSCoV2” OR “SARSCoV2” OR SARSCov19 OR “SARS-Cov19” OR “SARS-Cov-19”) OR “severe acute respiratory syndrome*” OR ((corona* OR corono*) AND (virus* OR viral* OR virinae*)) AND ((“lung injury”) OR (“ventilation use”) OR (“respiratory injuries” OR prone)) AND (treatment)) NOT Drugs NOT medicines NOT antivirals. Results A total of 28 articles were selected. These articles adopted one or more treatment methods for patients with severe cases of COVID-19, i.e., oxygen therapy, prone position, inhaled nitric oxide, intravenous infusion, passive immunotherapy, mesenchymal stem cells (MSC). Conclusion There is still no specific treatment approved for patients with COVID-19. The available evidence is not able yet to indicate the benefits or harms of non-pharmacological treatments, but some studies show that some treatments can play an important role in relation to COVID-19. The current consensus among researchers is that several studies using a randomized clinical trial should be carried out to provide evidence of safety and efficacy of the proposed treatments.
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Affiliation(s)
- Adriano Alves Pereira
- Centre for Innovation and Technology Assessment in Health, Faculty of Electrical Engineering, Federal University of Uberlândia, Uberlândia, Brazil
| | - Adriano de Oliveira Andrade
- Centre for Innovation and Technology Assessment in Health, Faculty of Electrical Engineering, Federal University of Uberlândia, Uberlândia, Brazil
| | - Angélica de Andrade Palis
- Centre for Innovation and Technology Assessment in Health, Faculty of Electrical Engineering, Federal University of Uberlândia, Uberlândia, Brazil
| | - Ariana Moura Cabral
- Centre for Innovation and Technology Assessment in Health, Faculty of Electrical Engineering, Federal University of Uberlândia, Uberlândia, Brazil
| | - Cassiana Gabriela Lima Barreto
- Centre for Innovation and Technology Assessment in Health, Faculty of Electrical Engineering, Federal University of Uberlândia, Uberlândia, Brazil
| | - Daniel Baldoino de Souza
- Centre for Innovation and Technology Assessment in Health, Faculty of Electrical Engineering, Federal University of Uberlândia, Uberlândia, Brazil
| | - Fernanda de Paula Silva
- Centre for Innovation and Technology Assessment in Health, Faculty of Electrical Engineering, Federal University of Uberlândia, Uberlândia, Brazil
| | - Fernando Pasquini Santos
- Centre for Innovation and Technology Assessment in Health, Faculty of Electrical Engineering, Federal University of Uberlândia, Uberlândia, Brazil
| | - Gabriella Lelis Silva
- Centre for Innovation and Technology Assessment in Health, Faculty of Electrical Engineering, Federal University of Uberlândia, Uberlândia, Brazil
| | - José Flávio Viana Guimarães
- Centre for Innovation and Technology Assessment in Health, Faculty of Electrical Engineering, Federal University of Uberlândia, Uberlândia, Brazil
| | - Laureane Almeida Santiago de Araújo
- Centre for Innovation and Technology Assessment in Health, Faculty of Electrical Engineering, Federal University of Uberlândia, Uberlândia, Brazil
| | - Lígia Reis Nóbrega
- Centre for Innovation and Technology Assessment in Health, Faculty of Electrical Engineering, Federal University of Uberlândia, Uberlândia, Brazil
| | - Luanne Cardoso Mendes
- Centre for Innovation and Technology Assessment in Health, Faculty of Electrical Engineering, Federal University of Uberlândia, Uberlândia, Brazil
| | - Mariana Ribeiro Brandão
- Institute of Biomedical Engineering, Federal University of Santa Catarina, Florianopolis, Brazil
| | - Selma Terezinha Milagre
- Centre for Innovation and Technology Assessment in Health, Faculty of Electrical Engineering, Federal University of Uberlândia, Uberlândia, Brazil
| | - Verônica de Lima Gonçalves
- Centre for Innovation and Technology Assessment in Health, Faculty of Electrical Engineering, Federal University of Uberlândia, Uberlândia, Brazil
| | | | - Viviane da Conceição Lima
- Centre for Innovation and Technology Assessment in Health, Faculty of Electrical Engineering, Federal University of Uberlândia, Uberlândia, Brazil
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23
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Golshani M, Hrdý J. Multiple Sclerosis Patients and Disease Modifying Therapies: Impact on Immune Responses against COVID-19 and SARS-CoV-2 Vaccination. Vaccines (Basel) 2022; 10:vaccines10020279. [PMID: 35214735 PMCID: PMC8876554 DOI: 10.3390/vaccines10020279] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Revised: 02/01/2022] [Accepted: 02/09/2022] [Indexed: 02/04/2023] Open
Abstract
This article reviews the literature on SARS-CoV-2 pandemic and multiple sclerosis (MS). The first part of the paper focuses on the current data on immunopathology of SARS-CoV-2 and leading vaccines produced against COVID-19 infection. In the second part of the article, we discuss the effect of Disease Modifying Therapies (DMTs) on COVID-19 infection severity or SARS-CoV-2 vaccination in MS patients plus safety profile of different vaccine platforms in MS patients.
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Affiliation(s)
| | - Jiří Hrdý
- Correspondence: ; Tel.: +420-224968509
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24
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Marchetti C, Vaglietti S, Rizzo F, Di Nardo G, Colnaghi L, Ghirardi M, Fiumara F. Heptad stereotypy, S/Q layering, and remote origin of the SARS-CoV-2 fusion core. Virus Evol 2022; 7:veab097. [PMID: 35039783 PMCID: PMC8754743 DOI: 10.1093/ve/veab097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Revised: 10/24/2021] [Accepted: 11/23/2021] [Indexed: 11/13/2022] Open
Abstract
The fusion of the SARS-CoV-2 virus with cells, a key event in the pathogenesis of Covid-19, depends on the assembly of a six-helix fusion core (FC) formed by portions of the spike protein heptad repeats (HRs) 1 and 2. Despite the critical role in regulating infectivity, its distinctive features, origin, and evolution are scarcely understood. Thus, we undertook a structure-guided positional and compositional analysis of the SARS-CoV-2 FC, in comparison with FCs of related viruses, tracing its origin and ongoing evolution. We found that clustered amino acid substitutions within HR1, distinguishing SARS-CoV-2 from SARS-CoV-1, enhance local heptad stereotypy and increase sharply the FC serine-to-glutamine (S/Q) ratio, determining a neat alternate layering of S-rich and Q-rich subdomains along the post-fusion structure. Strikingly, SARS-CoV-2 ranks among viruses with the highest FC S/Q ratio, together with highly syncytiogenic respiratory pathogens (RSV, NDV), whereas MERS-Cov, HIV, and Ebola viruses display low ratios, and this feature reflects onto S/Q segregation and H-bonding patterns. Our evolutionary analyses revealed that the SARS-CoV-2 FC occurs in other SARS-CoV-1-like Sarbecoviruses identified since 2005 in Hong Kong and adjacent regions, tracing its origin to >50 years ago with a recombination-driven spread. Finally, current mutational trends show that the FC is varying especially in the FC1 evolutionary hotspot. These findings establish a novel analytical framework illuminating the sequence/structure evolution of the SARS-CoV-2 FC, tracing its long history within Sarbecoviruses, and may help rationalize the evolution of the fusion machinery in emerging pathogens and the design of novel therapeutic fusion inhibitors.
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Affiliation(s)
- Chiara Marchetti
- Rita Levi Montalcini Department of Neuroscience, University of Torino, Corso Raffaello 30, Torino 10125, Italy
| | - Serena Vaglietti
- Rita Levi Montalcini Department of Neuroscience, University of Torino, Corso Raffaello 30, Torino 10125, Italy
| | - Francesca Rizzo
- Istituto Zooprofilattico Sperimentale (IZS) del Piemonte, Liguria e Valle d'Aosta, Via Bologna 148, Torino 10148, Italy
| | - Giovanna Di Nardo
- Department of Life Sciences and Systems Biology (DBIOS), University of Torino, Via Accademia Albertina 13, Torino 10123, Italy
| | - Luca Colnaghi
- Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, Milano 20132, Italy
| | - Mirella Ghirardi
- Rita Levi Montalcini Department of Neuroscience, University of Torino, Corso Raffaello 30, Torino 10125, Italy
| | - Ferdinando Fiumara
- Rita Levi Montalcini Department of Neuroscience, University of Torino, Corso Raffaello 30, Torino 10125, Italy
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25
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Niknam Z, Jafari A, Golchin A, Danesh Pouya F, Nemati M, Rezaei-Tavirani M, Rasmi Y. Potential therapeutic options for COVID-19: an update on current evidence. Eur J Med Res 2022; 27:6. [PMID: 35027080 PMCID: PMC8755901 DOI: 10.1186/s40001-021-00626-3] [Citation(s) in RCA: 85] [Impact Index Per Article: 28.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2021] [Accepted: 12/23/2021] [Indexed: 12/14/2022] Open
Abstract
SARS-CoV-2, a novel coronavirus, is the agent responsible for the COVID-19 pandemic and is a major public health concern nowadays. The rapid and global spread of this coronavirus leads to an increase in hospitalizations and thousands of deaths in many countries. To date, great efforts have been made worldwide for the efficient management of this crisis, but there is still no effective and specific treatment for COVID-19. The primary therapies to treat the disease are antivirals, anti-inflammatories and respiratory therapy. In addition, antibody therapies currently have been a many active and essential part of SARS-CoV-2 infection treatment. Ongoing trials are proposed different therapeutic options including various drugs, convalescent plasma therapy, monoclonal antibodies, immunoglobulin therapy, and cell therapy. The present study summarized current evidence of these therapeutic approaches to assess their efficacy and safety for COVID-19 treatment. We tried to provide comprehensive information about the available potential therapeutic approaches against COVID-19 to support researchers and physicians in any current and future progress in treating COVID-19 patients.
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Affiliation(s)
- Zahra Niknam
- Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ameneh Jafari
- Advanced Therapy Medicinal Product (ATMP) Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran
| | - Ali Golchin
- Department of Clinical Biochemistry and Applied Cell Sciences, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Fahima Danesh Pouya
- Department of Biochemistry, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Mohadeseh Nemati
- Department of Biochemistry, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Mostafa Rezaei-Tavirani
- Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Yousef Rasmi
- Department of Biochemistry, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
- Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran.
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26
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Advances in Targeting ACE2 for Developing COVID-19 Therapeutics. Ann Biomed Eng 2022; 50:1734-1749. [PMID: 36261668 PMCID: PMC9581451 DOI: 10.1007/s10439-022-03094-w] [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: 08/31/2022] [Accepted: 09/29/2022] [Indexed: 01/01/2023]
Abstract
Since the onset of the coronavirus pandemic in December 2019, the SARS-CoV-2 virus has accounted for over 6.3 million lives resulting in the demand to develop novel therapeutic approaches to target and treat SARS-CoV-2. Improved understanding of viral entry and infection mechanisms has led to identifying different target receptors to mitigate infection in the host. Researchers have been working on identifying and targeting potential therapeutic target receptors utilizing different candidate drugs. Angiotensin-converting enzyme-2 (ACE2) has been known to perform critical functions in maintaining healthy cardiorespiratory function. However, ACE2 also functions as the binding site for the spike protein of SARS-CoV-2, allowing the virus to enter the cells and ensue infection. Therefore, drugs targeting ACE2 receptors can be considered as therapeutic candidates. Strategies targeting the level of ACE2 expression have been investigated and compared to other potential therapeutic targets, such as TMPRSS2, RdRp, and DPP4. This mini review discusses the key therapeutic approaches that target the ACE2 receptor, which is critical to the cellular entry and propagation of the novel SARS-CoV-2. In addition, we summarize the main advantages of ACE2 targeting against alternative approaches for the treatment of COVID-19.
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27
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Erdag E. The Concomitant Use o f Melatonin and Bebtelovimab as a Treatment Strategy for Omicron and Future Variants of Concern. INTERNATIONAL JOURNAL OF PHARMACEUTICAL RESEARCH AND ALLIED SCIENCES 2022. [DOI: 10.51847/rbpkn77cbg] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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28
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Sutradhar J, Sarkar BR. The Effect on the Immune System in the Human Body Due to COVID-19: An Insight on Traditional to Modern Approach as a Preventive Measure. J Pharmacopuncture 2021; 24:165-172. [PMID: 35028167 PMCID: PMC8716700 DOI: 10.3831/kpi.2021.24.4.165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2020] [Revised: 08/17/2021] [Accepted: 11/26/2021] [Indexed: 11/26/2022] Open
Abstract
The COVID-19, the most infectious pandemic disease arising due to SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) has caused huge issues globally. In this review, we discuss the impact of COVID-19 on the immune system of the human body and the protective mechanisms of the host immune system opposing viral infections. Here, we summarize the effect of the pandemic of the novel coronavirus disease on the immune system such as sleep and Behavioral Immune System (BIS) together with consideration of researcher’s observation points of view. We draw particular attention to recent up-to-date reports concerning COVID-19 drugs as well as information about the landscape document for COVID-19 vaccines released by WHO (World Health Organization), and some adverse events of COVID-19 vaccination. Additionally, can take part in the preventive appraise in opposition within this pandemic severe COVID-19 infections disease may affect some outcome in physical exercise, physical movement, healthy diets, and good nutrition are significant for supporting the immune systems and summarize AYUSH (Ayurveda, Yoga and Naturopathy, Unani, Siddha, and Homeopathy) Indian medicinal systems guidelines for immunity boosting procedures during COVID-19 pandemic.
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Affiliation(s)
- Jugal Sutradhar
- Harishchandra PG College, Institute of Pharmacy, Bawan Beegha, Varanasi, India
| | - Bapi Ray Sarkar
- Department of Pharmaceutical Technology, University of North Bengal (NBU), Raja Rammohunpur, Darjeeling, West Bengal, India
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29
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Hmadcha A, Soria B, Zhao RC, Smani T, Valverde I. Editorial: A Compendium of Recent Research on Stem Cell-Based Therapy for Covid-19. Front Cell Dev Biol 2021; 9:813384. [PMID: 34970555 PMCID: PMC8713248 DOI: 10.3389/fcell.2021.813384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Accepted: 11/18/2021] [Indexed: 11/13/2022] Open
Affiliation(s)
- Abdelkrim Hmadcha
- Department of Biotechnology, University of Alicante, Alicante, Spain
- University of Pablo de Olavide, Seville, Spain
- Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain
- *Correspondence: Abdelkrim Hmadcha,
| | - Bernat Soria
- University of Pablo de Olavide, Seville, Spain
- Department of Physiology, Institute of Bioengineering-ISABIAL, University Miguel Hernández School of Medicine, Alicante, Spain
| | - Robert C. Zhao
- Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China
- School of Life Sciences, Shanghai University, Shanghai, China
- International Society on Aging and Disease, Bryan, TX, United States
| | - Tarik Smani
- Cardiovascular Pathophysiology, Institute of Biomedicine of Seville, University Hospital of Virgen del Rocío, University of Seville, CSIC, Seville, Spain
- Department of Medical Physiology and Biophysics, University of Seville, Seville, Spain
| | - Israel Valverde
- Pediatric Cardiology Unit, Virgen del Rocio University Hospital, Seville, Spain
- Institute of Biomedicine of Seville, University Hospital of Virgen del Rocío, University of Seville, CSIC, Seville, Spain
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Gupta D, Sharma P, Singh M, Kumar M, Ethayathulla AS, Kaur P. Structural and functional insights into the spike protein mutations of emerging SARS-CoV-2 variants. Cell Mol Life Sci 2021; 78:7967-7989. [PMID: 34731254 PMCID: PMC11073194 DOI: 10.1007/s00018-021-04008-0] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 10/20/2021] [Accepted: 10/22/2021] [Indexed: 02/07/2023]
Abstract
Since the emergence of the first case of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), the viral genome has constantly undergone rapid mutations for better adaptation in the host system. These newer mutations have given rise to several lineages/ variants of the virus that have resulted in high transmission and virulence rates compared to the previously circulating variants. Owing to this, the overall caseload and related mortality have tremendously increased globally to > 233 million infections and > 4.7 million deaths as of Sept. 28th, 2021. SARS-CoV-2, Spike (S) protein binds to host cells by recognizing human angiotensin-converting enzyme 2 (hACE2) receptor. The viral S protein contains S1 and S2 domains that constitute the binding and fusion machinery, respectively. Structural analysis of viral S protein reveals that the virus undergoes conformational flexibility and dynamicity to interact with the hACE2 receptor. The SARS-CoV-2 variants and mutations might be associated with affecting the conformational plasticity of S protein, potentially linked to its altered affinity, infectivity, and immunogenicity. This review focuses on the current circulating variants of SARS-CoV-2 and the structure-function analysis of key S protein mutations linked with increased affinity, higher infectivity, enhanced transmission rates, and immune escape against this infection.
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Affiliation(s)
- Deepali Gupta
- Department of Biophysics, All India Institute of Medical Sciences, New Delhi,, Delhi, 110029, India
| | - Priyanka Sharma
- Department of Microbiology, All India Institute of Medical Sciences, New Delhi,, Delhi, 110029, India
| | - Mandeep Singh
- Department of Biophysics, All India Institute of Medical Sciences, New Delhi,, Delhi, 110029, India
| | - Mukesh Kumar
- Department of Biophysics, All India Institute of Medical Sciences, New Delhi,, Delhi, 110029, India
| | - A S Ethayathulla
- Department of Biophysics, All India Institute of Medical Sciences, New Delhi,, Delhi, 110029, India
| | - Punit Kaur
- Department of Biophysics, All India Institute of Medical Sciences, New Delhi,, Delhi, 110029, India.
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Yan D, Ra OH, Yan B. The nucleoside antiviral prodrug remdesivir in treating COVID-19 and beyond with interspecies significance. ANIMAL DISEASES 2021; 1:15. [PMID: 34778881 PMCID: PMC8422062 DOI: 10.1186/s44149-021-00017-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Accepted: 07/25/2021] [Indexed: 01/18/2023] Open
Abstract
Infectious pandemics result in hundreds and millions of deaths, notable examples of the Spanish Flu, the Black Death and smallpox. The current pandemic, caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), is unprecedented even in the historical term of pandemics. The unprecedentedness is featured by multiple surges, rapid identification of therapeutic options and accelerated development of vaccines. Remdesivir, originally developed for Ebola viral disease, is the first treatment of COVID-19 (Coronavirus disease 2019) approved by the United States Food and Drug Administration. As demonstrated by in vitro and preclinical studies, this therapeutic agent is highly potent with a broad spectrum activity against viruses from as many as seven families even cross species. However, randomized controlled trials have failed to confirm the efficacy and safety. Remdesivir improves some clinical signs but not critical parameters such as mortality. This antiviral agent is an ester/phosphorylation prodrug and excessive hydrolysis which increases cellular toxicity. Remdesivir is given intravenously, leading to concentration spikes and likely increasing the potential of hydrolysis-based toxicity. This review has proposed a conceptual framework for improving its efficacy and minimizing toxicity not only for the COVID-19 pandemic but also for future ones caused by remdesivir-sensitive viruses.
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Affiliation(s)
- Daisy Yan
- Sidney Kimmel Medical College, Thomas Jefferson University, 1025 Walnut St, Philadelphia, PA 19107 USA
| | - One Hyuk Ra
- Department of Anesthesiology, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115 USA
| | - Bingfang Yan
- Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH 45229 USA
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A Patent Review on the Therapeutic Application of Monoclonal Antibodies in COVID-19. Int J Mol Sci 2021; 22:ijms222111953. [PMID: 34769383 PMCID: PMC8584575 DOI: 10.3390/ijms222111953] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Revised: 10/24/2021] [Accepted: 11/02/2021] [Indexed: 12/17/2022] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains spike proteins that assist the virus in entering host cells. In the absence of a specific intervention, efforts are afoot throughout the world to find an effective treatment for SARS-CoV-2. Through innovative techniques, monoclonal antibodies (MAbs) are being designed and developed to block a particular pathway of SARS-CoV-2 infection. More than 100 patent applications describing the development of MAbs and their application against SARS-CoV-2 have been registered. Most of them target the receptor binding protein so that the interaction between virus and host cell can be prevented. A few monoclonal antibodies are also being patented for the diagnosis of SARS-CoV-2. Some of them, like Regeneron® have already received emergency use authorization. These protein molecules are currently preferred for high-risk patients such as those over 65 years old with compromised immunity and those with metabolic disorders such as obesity. Being highly specific in action, monoclonal antibodies offer one of the most appropriate interventions for both the prevention and treatment of SARS-CoV-2. Technological advancement has helped in producing highly efficacious MAbs. However, these agents are known to induce immunogenic and non-immunogenic reactions. More research and testing are required to establish the suitability of administering MAbs to all patients at risk of developing a severe illness. This patent study is focused on MAbs as a therapeutic option for treating COVID-19, as well as their invention, patenting information, and key characteristics.
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Farid N, Rola N, Koch EAT, Nakhoul N. Active vitamin D supplementation and COVID-19 infections: review. Ir J Med Sci 2021; 190:1271-1274. [PMID: 33409846 PMCID: PMC7787599 DOI: 10.1007/s11845-020-02452-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Accepted: 12/01/2020] [Indexed: 11/25/2022]
Abstract
SARS-CoV-2, causing the lethal disease COVid-19, is a public health emergency in the 2020 global pandemic. The outbreak and fast spreading of SARS-CoV-2 have a high morbidity and mortality specifically in elder patients with chronic diseases such as diabetes mellitus, arterial hypertension, chronic kidney disease, and organ transplanted patients with immunosuppressive therapy. Preliminary results support different treatments such as chloroquine and convalescent plasma infusion in severe cases, with good outcome. On the other hand, the efficacy of supplementation with active vitamin D, an immunomodulator hormone with antiinflammatory and antimicrobial effects, is unproven. A recent study reported that vitamin D attains antiviral effects, via blocking viral replication directly. SARS-CoV-2 primarily uses the immune evasion process during infection via the envelope spike glycoprotein, which is followed by a cytokine storm, causing severe acute respiratory disease syndrome and death. SARS-CoV-2, by using the well-known angiotensin-converting enzyme 2 by the protein spike, as the host receptor to enter into alveolar, myocardial, and renal epithelial cells, can be disrupted by vitamin D. However, the correlation between vitamin D levels and COVID-19 deaths in previous studies was insignificant. Retrospective studies demonstrated a correlation between vitamin D status and COVID-19 severity and mortality, while other studies did not find this correlation. Studies have shown that, vitamin D reduces the risk of acute viral respiratory tract infections and pneumonia via direct inhibition of viral replication, antiinflammatory and immunomodulatory effects. The data available today regarding the beneficial protective effect of vitamin D is unclear and with conflicting results. Large randomized control trials are necessary to test this hypothesis. In this review, we will explain the cross talk between the active vitamin D and the angiotensin-converting enzyme 2, and summarize the data from the literature.
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Affiliation(s)
- Nakhoul Farid
- Nephrology and Hypertension Division, Baruch Padeh Poriya medical Center, Erlangen, Germany.
- Diabetes and Metabolism Lab, Baruch Padeh Poriya Medical Center, Erlangen, Germany.
- Azrieli Faculty of Medicine, Bar Ilan University, Ramat-Gan, Israel.
| | - Nakhoul Rola
- Department of Anaesthesiology, University Hospital Erlangen, Erlangen, Germany
| | - Elias A T Koch
- Department of Dermatology, University Hospital Erlangen, Erlangen, Germany
| | - Nakhoul Nakhoul
- Ophtalmology Division, Baruch Padeh Poriya Medical Center, Ramat-Gan, Israel
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Shekhawat J, Gauba K, Gupta S, Purohit P, Mitra P, Garg M, Misra S, Sharma P, Banerjee M. Interleukin-6 Perpetrator of the COVID-19 Cytokine Storm. Indian J Clin Biochem 2021; 36:440-450. [PMID: 34177139 PMCID: PMC8216093 DOI: 10.1007/s12291-021-00989-8] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Accepted: 06/08/2021] [Indexed: 12/21/2022]
Abstract
COVID-19 has emerged as a global pandemic. It is mainly manifested as pneumonia which may deteriorate into severe respiratory failure. The major hallmark of the disease is the systemic inflammatory immune response characterized by Cytokine Storm (CS). CS is marked by elevated levels of inflammatory cytokines, mainly interleukin-6 (IL-6), IL-8, IL-10, tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). Of these, IL-6 is found to be significantly associated with higher mortality. IL-6 is also a robust marker for predicting disease prognosis and deterioration of clinical profile. In this review, the pivotal role played by IL-6 in the immuno-pathology of COVID-19 has been illustrated. The role of IL-6 as a pleiotropic cytokine executing both pro and anti-inflammatory activities has been reviewed. ADAM 10, a metalloproteinase switches the anti-inflammatory pathway of IL-6 to pro inflammatory hence blocking the action of ADAM 10 could be a new therapeutic strategy to mitigate the proinflammatory action of IL-6. Furthermore, we explore the role of anti-IL6 agents, IL-6 receptor antibodies which were being used for autoimmune diseases but now are being repurposed for the therapy of COVID-19.
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Affiliation(s)
- Jyoti Shekhawat
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, 342005 India
| | - Kavya Gauba
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, 342005 India
| | - Shruti Gupta
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, 342005 India
| | - Purvi Purohit
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, 342005 India
| | - Prasenjit Mitra
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, 342005 India
| | - Mahendra Garg
- Department of Endocrinology, All India Institute of Medical Sciences, Jodhpur, 342005 India
| | - Sanjeev Misra
- Department of Surgical Oncology, All India Institute of Medical Sciences, Jodhpur, 342005 India
| | - Praveen Sharma
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, 342005 India
| | - Mithu Banerjee
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, 342005 India
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Choi S, Hwang S, Kwon K. Compassionate Use of GC5131 (Hyperimmunoglobulin) Therapy in Critically Ill Patients Diagnosed with COVID-19: A Case Series and Review of Literature. Viruses 2021; 13:v13091826. [PMID: 34578407 PMCID: PMC8473256 DOI: 10.3390/v13091826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 09/07/2021] [Accepted: 09/08/2021] [Indexed: 11/16/2022] Open
Abstract
Presently, the use of convalescent plasma and hyperimmunoglobulin obtained from individuals who have recovered from coronavirus disease 2019 (COVID-19) has proved to potentially provide passive antibody-based immunity, thereby leading to several clinical trials to develop an immune-based COVID-19 treatment. However, the therapeutic efficacy of hyperimmunoglobulin in critically ill patients with COVID-19 remains unknown. On 23 October 2020, we first administered GC5131 in a compassionate-use program to critically ill patients at the Kyungpook National University, Chilgok Hospital, Korea. Since then, five more critically ill patients were treated with GC5131 in this compassionate-use program in our hospital up until 17 December 2020. We retrospectively reviewed the clinical responses of six critically ill patients diagnosed with COVID-19 who received the hyperimmunoglobulin concentrate, GC5131, which was produced by the Green Cross Corporation. After the administration of GC5131, five patients died due to an exacerbation of COVID-19 pneumonia. GC5131 was ineffective when administered to critically ill patients with COVID-19. Nevertheless, we propose that to expect a therapeutic effect from GC5131, it should be administered as early as possible to avoid the excessive inflammatory response phase in patients with severe and advanced COVID-19 infection. This step was difficult to achieve in the real world due to the time required for decision making and the process of the compassionate-use program.
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Affiliation(s)
- Sunha Choi
- Division of Pulmonary Disease, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu 47404, Korea;
| | - Soyoon Hwang
- Division of Infectious Diseases, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu 47404, Korea;
| | - Kitae Kwon
- Division of Infectious Diseases, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu 47404, Korea;
- Correspondence: ; Tel.: +82-53-200-2616
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36
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Daly S, O’Sullivan A, MacLoughlin R. Cellular Immunotherapy and the Lung. Vaccines (Basel) 2021; 9:1018. [PMID: 34579255 PMCID: PMC8473388 DOI: 10.3390/vaccines9091018] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 09/08/2021] [Accepted: 09/10/2021] [Indexed: 02/07/2023] Open
Abstract
The new era of cellular immunotherapies has provided state-of-the-art and efficient strategies for the prevention and treatment of cancer and infectious diseases. Cellular immunotherapies are at the forefront of innovative medical care, including adoptive T cell therapies, cancer vaccines, NK cell therapies, and immune checkpoint inhibitors. The focus of this review is on cellular immunotherapies and their application in the lung, as respiratory diseases remain one of the main causes of death worldwide. The ongoing global pandemic has shed a new light on respiratory viruses, with a key area of concern being how to combat and control their infections. The focus of cellular immunotherapies has largely been on treating cancer and has had major successes in the past few years. However, recent preclinical and clinical studies using these immunotherapies for respiratory viral infections demonstrate promising potential. Therefore, in this review we explore the use of multiple cellular immunotherapies in treating viral respiratory infections, along with investigating several routes of administration with an emphasis on inhaled immunotherapies.
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Affiliation(s)
- Sorcha Daly
- College of Medicine, Nursing & Health Sciences, National University of Ireland, H91 TK33 Galway, Ireland;
| | - Andrew O’Sullivan
- Research and Development, Science and Emerging Technologies, Aerogen Limited, Galway Business Park, H91 HE94 Galway, Ireland;
| | - Ronan MacLoughlin
- Research and Development, Science and Emerging Technologies, Aerogen Limited, Galway Business Park, H91 HE94 Galway, Ireland;
- School of Pharmacy and Pharmaceutical Sciences, Trinity College, D02 PN40 Dublin, Ireland
- School of Pharmacy & Biomolecular Sciences, Royal College of Surgeons in Ireland, D02 YN77 Dublin, Ireland
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37
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Johnson AM, Barigye R, Saminathan H. Perspectives on the use and risk of adverse events associated with cytokine-storm targeting antibodies and challenges associated with development of novel monoclonal antibodies for the treatment of COVID-19 clinical cases. Hum Vaccin Immunother 2021; 17:2824-2840. [PMID: 33974497 PMCID: PMC8127167 DOI: 10.1080/21645515.2021.1908060] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 03/02/2021] [Accepted: 03/19/2021] [Indexed: 02/06/2023] Open
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the novel coronavirus disease 2019 (COVID-19) pandemic that lacks globally accessible effective antivirals or extensively available vaccines. Numerous clinical trials are exploring the applicability of repurposed monoclonal antibodies (mAbs) targeting cytokines that cause adverse COVID-19-related pathologies, and novel mAbs directly targeting SARS-CoV-2. However, comorbidities and the incidence of cytokine storm (CS)-associated pathological complexities in some COVID-19 patients may limit the clinical use of these drugs. Additionally, CS-targeting mAbs have the potential to cause adverse events that restrict their applicability in patients with comorbidities. Novel mAbs targeting SARS-CoV-2 require pharmacological and toxicological characterization before a marketable product becomes available. The affordability of novel mAbs across the global economic spectrum may seriously limit their accessibility. This review presents a perspective on antibody-based research efforts and their limitations for COVID-19.
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Affiliation(s)
- Aishwarya Mary Johnson
- Department of Veterinary Medicine, College of Food and Agriculture, United Arab Emirates University, Abu Dhabi, United Arab Emirates
| | - Robert Barigye
- Department of Veterinary Medicine, College of Food and Agriculture, United Arab Emirates University, Abu Dhabi, United Arab Emirates
| | - Hariharan Saminathan
- Department of Veterinary Medicine, College of Food and Agriculture, United Arab Emirates University, Abu Dhabi, United Arab Emirates
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Pal S, Islam N, Misra S. VIVID: In Vivo End-to-End Molecular Communication Model for COVID-19. IEEE TRANSACTIONS ON MOLECULAR, BIOLOGICAL, AND MULTI-SCALE COMMUNICATIONS 2021; 7:142-152. [PMID: 35782712 PMCID: PMC8544951 DOI: 10.1109/tmbmc.2021.3071767] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Revised: 01/24/2021] [Accepted: 03/23/2021] [Indexed: 12/23/2022]
Abstract
As an alternative to ongoing efforts for vaccine development, scientists are exploring novel approaches to provide innovative therapeutics, such as nanoparticle- and stem cell-based treatments. Thus, understanding the transmission and propagation dynamics of coronavirus inside the respiratory system has attracted researchers' attention. In this work, we model the transmission and propagation of coronavirus inside the respiratory tract, starting from the nasal area to alveoli using molecular communication theory. We performed experiments using COMSOL, a finite-element multiphysics simulation software, and Python-based simulations to analyze the end-to-end communication model in terms of path loss, delay, and gain. The analytical results show the correlation between the channel characteristics and pathophysiological properties of coronavirus. For the initial 50% of the maximum production rate of virus particles, the path loss increases more than 16 times than the remaining 50%. The delayed response of the immune system and increase in the absorption of virus particles inside the respiratory tract delay the arrival of virus particles at the alveoli. Furthermore, the results reveal that the virus load is more in case of asthmatic patients as compared to the normal subjects.
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Affiliation(s)
- Saswati Pal
- School of Nano-Science and TechnologyIndian Institute of Technology KharagpurKharagpur721302India
| | - Nabiul Islam
- Telecommunications Software and Systems GroupWaterford Institute of TechnologyWaterfordX91 WR86Ireland
| | - Sudip Misra
- Department of Computer Science and EngineeringIndian Institute of Technology KharagpurKharagpur721302India
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Mehata AK, Viswanadh MK, Priya V, Vikas, Muthu MS. Harnessing immunological targets for COVID-19 immunotherapy. Future Virol 2021. [PMID: 34447458 PMCID: PMC8375415 DOI: 10.2217/fvl-2021-0048] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Accepted: 07/16/2021] [Indexed: 12/22/2022]
Abstract
COVID-19 is an infectious and highly contagious disease caused by SARS-CoV-2. The immunotherapy strategy has a great potential to develop a permanent cure against COVID-19. Innate immune cells are in constant motion to scan molecular alteration to cells led by microbial infections throughout the body and helps in clearing invading viruses. Harnessing immunological targets for removing viral infection, generally based on the principle of enhancing the T-cell and protective immune responses. Currently-approved COVID-19 vaccines are mRNA encapsulated in liposomes that stimulate the host immune system to produce antibodies. Given the vital role of innate immunity, harnessing these immune responses opens up new hope for the generation of long-lasting and protective immunity against COVID-19.
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Affiliation(s)
- Abhishesh Kumar Mehata
- Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (BHU), Varanasi, 221005, India
| | - Matte Kasi Viswanadh
- Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (BHU), Varanasi, 221005, India
| | - Vishnu Priya
- Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (BHU), Varanasi, 221005, India
| | - Vikas
- Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (BHU), Varanasi, 221005, India
| | - Madaswamy S Muthu
- Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (BHU), Varanasi, 221005, India
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40
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Shanmugaraj B, Siriwattananon K, Malla A, Phoolcharoen W. Potential for Developing Plant-Derived Candidate Vaccines and Biologics against Emerging Coronavirus Infections. Pathogens 2021; 10:1051. [PMID: 34451516 PMCID: PMC8400130 DOI: 10.3390/pathogens10081051] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Revised: 08/13/2021] [Accepted: 08/17/2021] [Indexed: 01/03/2023] Open
Abstract
The emerging human coronavirus infections in the 21st century remain a major public health crisis causing worldwide impact and challenging the global health care system. The virus is circulating in several zoonotic hosts and continuously evolving, causing occasional outbreaks due to spill-over events occurring between animals and humans. Hence, the development of effective vaccines or therapeutic interventions is the current global priority in order to reduce disease severity, frequent outbreaks, and to prevent future infections. Vaccine development for newly emerging pathogens takes a long time, which hinders rapid immunization programs. The concept of plant-based pharmaceuticals can be readily applied to meet the recombinant protein demand by means of transient expression. Plants are evolved as an expression platform, and they bring a combination of unique interests in terms of rapid scalability, flexibility, and economy for industrial-scale production of effective vaccines, diagnostic reagents, and other biopharmaceuticals. Plants offer safe biologics to fulfill emergency demands, especially during pandemic situations or outbreaks caused by emerging strains. This review highlights the features of a plant expression platform for producing recombinant biopharmaceuticals to combat coronavirus infections with emphasis on COVID-19 vaccine and biologics development.
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Affiliation(s)
| | - Konlavat Siriwattananon
- Research Unit for Plant-Produced Pharmaceuticals, Chulalongkorn University, Bangkok 10330, Thailand;
- Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand
| | - Ashwini Malla
- Baiya Phytopharm Co., Ltd., Bangkok 10250, Thailand; (B.S.); (A.M.)
| | - Waranyoo Phoolcharoen
- Baiya Phytopharm Co., Ltd., Bangkok 10250, Thailand; (B.S.); (A.M.)
- Research Unit for Plant-Produced Pharmaceuticals, Chulalongkorn University, Bangkok 10330, Thailand;
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41
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Rattanapisit K, Bulaon CJI, Khorattanakulchai N, Shanmugaraj B, Wangkanont K, Phoolcharoen W. Plant-produced SARS-CoV-2 receptor binding domain (RBD) variants showed differential binding efficiency with anti-spike specific monoclonal antibodies. PLoS One 2021; 16:e0253574. [PMID: 34379620 PMCID: PMC8357147 DOI: 10.1371/journal.pone.0253574] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Accepted: 06/09/2021] [Indexed: 11/18/2022] Open
Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the ongoing coronavirus disease (COVID-19) pandemic which is characterized by respiratory illness and severe pneumonia, and currently accounts for > 2.5 million deaths worldwide. Recently, diverse mutations in the spike protein of SARS-CoV-2 were reported in United Kingdom (Alpha) and South Africa (Beta) strains which raise concerns over the potential increase in binding affinity towards the host cell receptor and diminished host neutralization capabilities. In order to study the effect of mutation in the binding efficiency of SARS-CoV-2 receptor binding domain (RBD) with anti-SARS-CoV/CoV-2 monoclonal antibodies (mAbs), we have produced SARS-CoV-2 RBD and two variants SARS-CoV-2 RBD (Alpha RBD and Beta RBD) in Nicotiana benthamiana by transient expression. Plant-produced SARS-CoV-2 RBD-Fc, Alpha RBD-Fc and Beta RBD-Fc exhibited specific binding to human angiotensin converting enzyme 2 (ACE2) receptor determined by ELISA. Intriguingly, the binding of plant-produced SARS-CoV-2 RBD proteins to plant-produced mAbs CR3022, B38, and H4 was found to be different depending on the variant mutation. In contrary to the plant-produced SARS-CoV-2 RBD-Fc and Alpha RBD-Fc, Beta RBD-Fc variant showed weak binding affinity towards the mAbs. The result suggested that the Beta RBD variant might have acquired partial resistance to neutralizing antibodies compared to other variants. However, further studies with sera from convalescent or vaccinated individuals are required to confirm this finding.
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Affiliation(s)
| | - Christine Joy I. Bulaon
- Research Unit for Plant-produced Pharmaceuticals, Chulalongkorn University, Bangkok, Thailand
- Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
| | - Narach Khorattanakulchai
- Research Unit for Plant-produced Pharmaceuticals, Chulalongkorn University, Bangkok, Thailand
- Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
| | | | - Kittikhun Wangkanont
- Center of Excellence for Molecular Biology and Genomics of Shrimp (GCE 6302823006-1), Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand
- Molecular Crop Research Unit (GRU 6407023008-1), Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand
- Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand
| | - Waranyoo Phoolcharoen
- Research Unit for Plant-produced Pharmaceuticals, Chulalongkorn University, Bangkok, Thailand
- Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
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Esposito S, Abu-Raya B, Bonanni P, Cahn-Sellem F, Flanagan KL, Martinon Torres F, Mejias A, Nadel S, Safadi MAP, Simon A. Coadministration of Anti-Viral Monoclonal Antibodies With Routine Pediatric Vaccines and Implications for Nirsevimab Use: A White Paper. Front Immunol 2021; 12:708939. [PMID: 34456918 PMCID: PMC8386277 DOI: 10.3389/fimmu.2021.708939] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 07/15/2021] [Indexed: 02/01/2023] Open
Abstract
Routine childhood vaccinations are key for the protection of children from a variety of serious and potentially fatal diseases. Current pediatric vaccine schedules mainly cover active vaccines. Active vaccination in infants is a highly effective approach against several infectious diseases; however, thus far, for some important viral pathogens, including respiratory syncytial virus (RSV), vaccine development and license by healthcare authorities have not been accomplished. Nirsevimab is a human-derived, highly potent monoclonal antibody (mAb) with an extended half-life for RSV prophylaxis in all infants. In this manuscript, we consider the potential implications for the introduction of an anti-viral mAb, such as nirsevimab, into the routine pediatric vaccine schedule, as well as considerations for coadministration. Specifically, we present evidence on the general mechanism of action of anti-viral mAbs and experience with palivizumab, the only approved mAb for the prevention of RSV infection in preterm infants, infants with chronic lung disease of prematurity and certain infants with hemodynamically significant heart disease. Palivizumab has been used for over two decades in infants who also receive routine vaccinations without any alerts concerning the safety and efficacy of coadministration. Immunization guidelines (Advisory Committee on Immunization Practices, Joint Committee on Vaccination and Immunization, National Advisory Committee on Immunization, Centers for Disease Control and Prevention, American Academy of Pediatrics, The Association of the Scientific Medical Societies in Germany) support coadministration of palivizumab with routine pediatric vaccines, noting that immunobiologics, such as palivizumab, do not interfere with the immune response to licensed live or inactivated active vaccines. Based on the mechanism of action of the new generation of anti-viral mAbs, such as nirsevimab, which is highly specific targeting viral antigenic sites, it is unlikely that it could interfere with the immune response to other vaccines. Taken together, we anticipate that nirsevimab could be concomitantly administered to infants with routine pediatric vaccines during the same clinic visit.
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Affiliation(s)
- Susanna Esposito
- Pediatric Clinic, University Hospital, Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Bahaa Abu-Raya
- Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada
| | - Paolo Bonanni
- Specialization Medical School of Hygiene, Department of Health Sciences, University of Florence, Florence, Italy
| | | | - Katie L. Flanagan
- Tasmanian Vaccine Trial Centre, Launceston General Hospital, Launceston, TAS, Australia
- School of Medicine, University of Tasmania, Launceston, TAS, Australia
- Department of Immunology and Pathology, Monash University, Melbourne, VIC, Australia
- School of Health and Biomedical Science, Royal Melbourne Institute of Technology (RMIT) University, Melbourne, VIC, Australia
| | - Federico Martinon Torres
- Translational Pediatrics and Infectious Diseases, Pediatrics Department, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain
- Genetics, Vaccines and Pediatrics Research Group, Instituto de Investigación Sanitaria de Santiago de Compostela, Universidad de Santiago, Santiago de Compostela, Spain
| | - Asuncion Mejias
- Division of Infectious Diseases, Department of Pediatrics, Center for Vaccines and Immunity Nationwide Children’s Hospital-The Ohio State University College of Medicine, Columbus, OH, United States
- Department of Pharmacology and Pediatrics, Malaga Medical School, Malaga University, Malaga, Spain
| | | | - Marco A. P. Safadi
- Department of Pediatrics, Santa Casa de Sao Paulo School of Medical Sciences, Sao Paulo, Brazil
| | - Arne Simon
- Klinik für Pädiatrische Onkologie und Hämatologie Universitätsklinikum des Saarlandes, Homburg, Germany
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Use of Monoclonal Antibody to Treat COVID-19 in Children and Adolescents: Risk of Abuse of Prescription and Exacerbation of Health Inequalities. Pharmaceuticals (Basel) 2021; 14:ph14070673. [PMID: 34358099 PMCID: PMC8308584 DOI: 10.3390/ph14070673] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Revised: 07/09/2021] [Accepted: 07/13/2021] [Indexed: 01/16/2023] Open
Abstract
Monoclonal antibodies (mAbs) that neutralize SARS-CoV-2 in infected patients are a new class of antiviral agents approved as a type of passive immunotherapy. They should be administered to adults and children (≥12 years old, weighing ≥ 40 kg) with SARS-CoV-2 positivity, and who are suffering from a chronic underlying disease and are at risk of severe COVID-19 and/or hospitalization. The aim of this manuscript is to discuss the benefit-to-risk of mAb therapy to treat COVID-19 in pediatric age, according to current reports. A problem is that the authorization for mAbs use in children was given without studies previously evaluating the efficacy, safety and tolerability of mAbs in pediatric patients. Moreover, although the total number of children with chronic severe underlying disease is not marginal, the risk of severe COVID-19 in pediatric age is significantly reduced than in adults and the role of chronic underlying disease as a risk factor of severe COVID-19 development in pediatric patients is far from being precisely defined. In addition, criteria presently suggested for use of mAbs in children and adolescents are very broad and may cause individual clinicians or institutions to recommend these agents on a case-by-case basis, with an abuse in mAbs prescriptions and an exacerbation of health inequalities while resources are scarce. Several questions need to be addressed before their routine use in clinical practice, including what is their associated benefit-to-risk ratio in children and adolescents, who are the patients that could really have benefit from their use, and if there is any interference of mAb therapy on recommended vaccines. While we wait for answers to these questions from well-conducted research, an effective and safe COVID-19 vaccine for vulnerable pediatric patients remains the best strategy to prevent COVID-19 and represents the priority for public health policies.
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COVID-19 and male reproductive system: pathogenic features and possible mechanisms. J Mol Histol 2021; 52:869-878. [PMID: 34232425 PMCID: PMC8260577 DOI: 10.1007/s10735-021-10003-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Accepted: 06/28/2021] [Indexed: 12/30/2022]
Abstract
Multiorgan dysfunction is the main characteristic of severe COVID-19 patients and the involvement of male reproductive system may occur among these patients. Although there is a limited evidence to confirm the orchitis and virus presence in the semen of patients, there are concerns about the transmission of virus through the semen. In addition, reduced fertility or infertility can be seen as consequences of severe COVID-19 in recovered subjects. In this study, we aimed to review articles related to COVID-19 and male reproductive system to find the possible underlying mechanisms of SARS-CoV-2 in affecting male fertility. The following keywords of SARS-CoV-2, COVID-19, testis, orchitis, semen, angiotensin-converting enzyme 2 (ACE2), hypothalamic-pituitary-testicular (HPT) axis, Hypothalamus, etc., were defined to find the related publications from standard search engines, e.g., PUBMED, SCOPUS, Google Scholar. According to studies, COVID-19 occurs in severe patients as respiratory disease, along with multi-organ failure. The most important mechanisms are classified as direct and indirect pathogenesis of SARS-CoV-2. The presence of ACE2 on the cell surface of various cells in testis increases the risk of direct infection by this virus. SARS-CoV-2 also affects the testis through the cytokine storm. In addition, the important role of HPT axis dysregulation through impaired Leydig cells and hypothalamus should be considered. Using antiviral and immunomodulatory therapy can be harmful for testis function. Further investigations are required to investigate potential mechanisms of male infertility in survivals of COVID-19. Since involvement of testis is essential for fertility, increasing the knowledge of health system may improve the outcomes.
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Siriwattananon K, Manopwisedjaroen S, Shanmugaraj B, Prompetchara E, Ketloy C, Buranapraditkun S, Tharakhet K, Kaewpang P, Ruxrungtham K, Thitithanyanont A, Phoolcharoen W. Immunogenicity Studies of Plant-Produced SARS-CoV-2 Receptor Binding Domain-Based Subunit Vaccine Candidate with Different Adjuvant Formulations. Vaccines (Basel) 2021; 9:744. [PMID: 34358160 PMCID: PMC8310282 DOI: 10.3390/vaccines9070744] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Revised: 06/28/2021] [Accepted: 07/03/2021] [Indexed: 12/23/2022] Open
Abstract
Due to the rapid transmission of the coronavirus disease 2019 (COVID-19) causing serious public health problems and economic burden, the development of effective vaccines is a high priority for controlling the virus spread. Our group has previously demonstrated that the plant-produced receptor-binding domain (RBD) of SARS-CoV-2 fused with Fc of human IgG was capable of eliciting potent neutralizing antibody and cellular immune responses in animal studies, and the immunogenicity could be improved by the addition of an alum adjuvant. Here, we performed a head-to-head comparison of different commercially available adjuvants, including aluminum hydroxide gel (alum), AddaVax (MF59), monophosphoryl lipid A from Salmonella minnesota R595 (mPLA-SM), and polyinosinic-polycytidylic acid (poly(I:C)), in mice by combining them with plant-produced RBD-Fc, and the differences in the immunogenicity of RBD-Fc with different adjuvants were evaluated. The specific antibody responses in terms of total IgG, IgG1, and IgG2a subtypes and neutralizing antibodies, as well as vaccine-specific T-lymphocyte responses, induced by the different tested adjuvants were compared. We observed that all adjuvants tested here induced a high level of total IgG and neutralizing antibodies, but mPLA-SM and poly (I:C) showed the induction of a balanced IgG1 and IgG2a (Th2/Th1) immune response. Further, poly (I:C) significantly increased the frequency of IFN-γ-expressing cells compared with control, whereas no significant difference was observed between the adjuvanted groups. This data revealed the adjuvants' role in enhancing the immune response of RBD-Fc vaccination and the immune profiles elicited by different adjuvants, which could prove helpful for the rational development of next-generation SARS-CoV-2 RBD-Fc subunit vaccines. However, additional research is essential to further investigate the efficacy and safety of this vaccine formulation before clinical trials.
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Affiliation(s)
- Konlavat Siriwattananon
- Research Unit for Plant-Produced Pharmaceuticals, Chulalongkorn University, Bangkok 10330, Thailand;
- Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand
| | - Suwimon Manopwisedjaroen
- Department of Microbiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand; (S.M.); (A.T.)
| | | | - Eakachai Prompetchara
- Center of Excellence in Vaccine Research and Development (Chula Vaccine Research Center, Chula VRC), Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand; (E.P.); (C.K.); (S.B.); (K.T.); (P.K.); (K.R.)
- Department of Laboratory Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
| | - Chutitorn Ketloy
- Center of Excellence in Vaccine Research and Development (Chula Vaccine Research Center, Chula VRC), Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand; (E.P.); (C.K.); (S.B.); (K.T.); (P.K.); (K.R.)
- Department of Laboratory Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
| | - Supranee Buranapraditkun
- Center of Excellence in Vaccine Research and Development (Chula Vaccine Research Center, Chula VRC), Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand; (E.P.); (C.K.); (S.B.); (K.T.); (P.K.); (K.R.)
- Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
| | - Kittipan Tharakhet
- Center of Excellence in Vaccine Research and Development (Chula Vaccine Research Center, Chula VRC), Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand; (E.P.); (C.K.); (S.B.); (K.T.); (P.K.); (K.R.)
| | - Papatsara Kaewpang
- Center of Excellence in Vaccine Research and Development (Chula Vaccine Research Center, Chula VRC), Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand; (E.P.); (C.K.); (S.B.); (K.T.); (P.K.); (K.R.)
| | - Kiat Ruxrungtham
- Center of Excellence in Vaccine Research and Development (Chula Vaccine Research Center, Chula VRC), Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand; (E.P.); (C.K.); (S.B.); (K.T.); (P.K.); (K.R.)
- Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
| | - Arunee Thitithanyanont
- Department of Microbiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand; (S.M.); (A.T.)
| | - Waranyoo Phoolcharoen
- Research Unit for Plant-Produced Pharmaceuticals, Chulalongkorn University, Bangkok 10330, Thailand;
- Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand
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Iqbal Yatoo M, Hamid Z, Rather I, Nazir QUA, Bhat RA, Ul Haq A, Magray SN, Haq Z, Sah R, Tiwari R, Natesan S, Bilal M, Harapan H, Dhama K. Immunotherapies and immunomodulatory approaches in clinical trials - a mini review. Hum Vaccin Immunother 2021; 17:1897-1909. [PMID: 33577374 PMCID: PMC7885722 DOI: 10.1080/21645515.2020.1871295] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Accepted: 12/28/2020] [Indexed: 12/13/2022] Open
Abstract
The coronavirus disease (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created havoc worldwide. Due to the non-availability of any vaccine or drugs against COVID-19, immunotherapies involving convalescent plasma, immunoglobulins, antibodies (monoclonal or polyclonal), and the use of immunomodulatory agents to enhance immunity are valuable alternative options. Cell-based therapies including natural killer cells, T cells, stem cells along with cytokines and toll-like receptors (TLRs) based therapies are also being exploited potentially against COVID-19. Future research need to strengthen the field of developing effective immunotherapeutics and immunomodulators with a thrust of providing appropriate, affordable, convenient, and cost-effective prophylactic and treatment regimens to combat global COVID-19 crisis that has led to a state of medical emergency enforcing entire countries of the world to devote their research infrastructure and manpower in tackling this pandemic.
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Affiliation(s)
- Mohd. Iqbal Yatoo
- Division of Veterinary Clinical Complex, Faculty of Veterinary Sciences and Animal Husbandry, Shuhama, Alusteng Srinagar, Sher-E-Kashmir University of Agricultural Sciences and Technology of Kashmir, Shalimar, Jammu and Kashmir, India
| | - Zeenat Hamid
- Department of Biotechnology, University of Kashmir, Jammu and Kashmir, India
| | - Izhar Rather
- Division of Veterinary Clinical Complex, Faculty of Veterinary Sciences and Animal Husbandry, Shuhama, Alusteng Srinagar, Sher-E-Kashmir University of Agricultural Sciences and Technology of Kashmir, Shalimar, Jammu and Kashmir, India
| | - Qurat Ul Ain Nazir
- Division of Veterinary Clinical Complex, Faculty of Veterinary Sciences and Animal Husbandry, Shuhama, Alusteng Srinagar, Sher-E-Kashmir University of Agricultural Sciences and Technology of Kashmir, Shalimar, Jammu and Kashmir, India
| | - Riyaz Ahmed Bhat
- Division of Veterinary Clinical Complex, Faculty of Veterinary Sciences and Animal Husbandry, Shuhama, Alusteng Srinagar, Sher-E-Kashmir University of Agricultural Sciences and Technology of Kashmir, Shalimar, Jammu and Kashmir, India
| | - Abrar Ul Haq
- Division of Veterinary Clinical Complex, Faculty of Veterinary Sciences and Animal Husbandry, Shuhama, Alusteng Srinagar, Sher-E-Kashmir University of Agricultural Sciences and Technology of Kashmir, Shalimar, Jammu and Kashmir, India
| | - Suhail Nabi Magray
- Division of Animal Biotechnology, Faculty of Veterinary Sciences and Animal Husbandry, Shuhama, Alusteng Srinagar, Sher-E-Kashmir University of Agricultural Sciences and Technology of Kashmir, Shalimar, Jammu and Kashmir, India
| | - Zulfqar Haq
- ICAR-Centre for Research on Poultry, Division of Livestock Production and Management, Faculty of Veterinary Sciences and Animal Husbandry, Shuhama, Alusteng Srinagar, Sher-E-Kashmir University of Agricultural Sciences and Technology of Kashmir, Shalimar, Jammu and Kashmir, India
| | - Ranjit Sah
- Tribhuvan University Teaching Hospital, Institute of Medicine, Kathmandu, Nepal
| | - Ruchi Tiwari
- Department of Veterinary Microbiology and Immunology, College of Veterinary Sciences, UP Pandit Deen Dayal Upadhayay Pashu Chikitsa Vigyan Vishwavidyalay Evum Go-Anusandhan Sansthan (DUVASU), Mathura, Uttar Pradesh, India
| | - SenthilKumar Natesan
- Department of Infectious Diseases, Indian Institute of Public Health Gandhinagar, Gandhinagar, Gujarat, India
| | - Muhammad Bilal
- School of Life Science and Food Engineering, Huaiyin Institute of Technology, Huaian, China
| | - Harapan Harapan
- Medical Research Unit, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia
- Tropical Disease Centre, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia
- Department of Microbiology, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia
| | - Kuldeep Dhama
- Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, India
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Ben-Zuk N, Dechtman ID, Henn I, Weiss L, Afriat A, Krasner E, Gal Y. Potential Prophylactic Treatments for COVID-19. Viruses 2021; 13:1292. [PMID: 34372498 PMCID: PMC8310088 DOI: 10.3390/v13071292] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2021] [Revised: 06/22/2021] [Accepted: 06/28/2021] [Indexed: 01/08/2023] Open
Abstract
The World Health Organization declared the SARS-CoV-2 outbreak a Public Health Emergency of International Concern at the end of January 2020 and a pandemic two months later. The virus primarily spreads between humans via respiratory droplets, and is the causative agent of Coronavirus Disease 2019 (COVID-19), which can vary in severity, from asymptomatic or mild disease (the vast majority of the cases) to respiratory failure, multi-organ failure, and death. Recently, several vaccines were approved for emergency use against SARS-CoV-2. However, their worldwide availability is acutely limited, and therefore, SARS-CoV-2 is still expected to cause significant morbidity and mortality in the upcoming year. Hence, additional countermeasures are needed, particularly pharmaceutical drugs that are widely accessible, safe, scalable, and affordable. In this comprehensive review, we target the prophylactic arena, focusing on small-molecule candidates. In order to consolidate a potential list of such medications, which were categorized as either antivirals, repurposed drugs, or miscellaneous, a thorough screening for relevant clinical trials was conducted. A brief molecular and/or clinical background is provided for each potential drug, rationalizing its prophylactic use as an antiviral or inflammatory modulator. Drug safety profiles are discussed, and current medical indications and research status regarding their relevance to COVID-19 are shortly reviewed. In the near future, a significant body of information regarding the effectiveness of drugs being clinically studied for COVID-19 is expected to accumulate, in addition to information regarding the efficacy of prophylactic treatments.
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Affiliation(s)
- Noam Ben-Zuk
- Chemical, Biological, Radiological and Nuclear Defense Division, Ministry of Defense, HaKirya, Tel-Aviv 61909, Israel; (N.B.-Z.); (I.H.); (L.W.)
| | - Ido-David Dechtman
- The Israel Defense Force Medical Corps, Tel Hashomer, Military Post 02149, Israel;
- Pulmonology Department, Edith Wolfson Medical Center, 62 Halochamim Street, Holon 5822012, Israel
| | - Itai Henn
- Chemical, Biological, Radiological and Nuclear Defense Division, Ministry of Defense, HaKirya, Tel-Aviv 61909, Israel; (N.B.-Z.); (I.H.); (L.W.)
| | - Libby Weiss
- Chemical, Biological, Radiological and Nuclear Defense Division, Ministry of Defense, HaKirya, Tel-Aviv 61909, Israel; (N.B.-Z.); (I.H.); (L.W.)
| | - Amichay Afriat
- Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, Israel;
| | - Esther Krasner
- Chemical, Biological, Radiological and Nuclear Defense Division, Ministry of Defense, HaKirya, Tel-Aviv 61909, Israel; (N.B.-Z.); (I.H.); (L.W.)
| | - Yoav Gal
- Chemical, Biological, Radiological and Nuclear Defense Division, Ministry of Defense, HaKirya, Tel-Aviv 61909, Israel; (N.B.-Z.); (I.H.); (L.W.)
- Israel Institute for Biological Research, Ness-Ziona 76100, Israel
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Di Pierro F, Iqtadar S, Khan A, Ullah Mumtaz S, Masud Chaudhry M, Bertuccioli A, Derosa G, Maffioli P, Togni S, Riva A, Allegrini P, Khan S. Potential Clinical Benefits of Quercetin in the Early Stage of COVID-19: Results of a Second, Pilot, Randomized, Controlled and Open-Label Clinical Trial. Int J Gen Med 2021; 14:2807-2816. [PMID: 34194240 PMCID: PMC8238537 DOI: 10.2147/ijgm.s318949] [Citation(s) in RCA: 117] [Impact Index Per Article: 29.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Accepted: 06/11/2021] [Indexed: 12/14/2022] Open
Abstract
Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing global pandemic known as COVID-19. Based on the potential antiviral role of quercetin, and on its described anti-blood clotting, anti-inflammatory and antioxidant properties, we hypothesize that subjects with mild COVID-19 treated with Quercetin Phytosome® (QP), a novel bioavailable form of quercetin, may have a shorter time to virus clearance, a milder symptomatology, and higher probabilities of a benign earlier resolution of the disease. Methods In our 2-week, randomized, open-label, and controlled clinical study, we have enrolled 42 COVID-19 outpatients. Twenty-one have been treated with the standard of care (SC), and 21 with QP as add-on supplementation to the SC. Our main aims were to check virus clearance and symptoms. Results The interim results reveal that after 1 week of treatment, 16 patients of the QP group were tested negative for SARS-CoV-2 and 12 patients had all their symptoms diminished; in the SC group, 2 patients were tested SARS-CoV-2 negative and 4 patients had their symptoms partially improved. By 2 weeks, the remaining 5 patients of the QP group tested negative for SARS-CoV-2, whereas in the SC group out of 19 remaining patients, 17 tested negatives by week 2, one tested negative by week 3 and one patient, still positive, expired by day 20. Concerning blood parameters, the add on therapy with QP, reduced LDH (−35.5%), Ferritin (−40%), CRP (−54.8%) and D-dimer (−11.9%). Conclusion QP statistically shortens the timing of molecular test conversion from positive to negative, reducing at the same time symptoms severity and negative predictors of COVID-19.
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Affiliation(s)
- Francesco Di Pierro
- Scientific & Research Department, Velleja Research, Milan, Italy.,Digestive Endoscopy, Fondazione Poliambulanza, Brescia, Italy
| | - Somia Iqtadar
- Department of Medicine, King Edward Medical University, Lahore, Pakistan
| | - Amjad Khan
- Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford, UK.,University of Health Sciences, Lahore, Pakistan
| | - Sami Ullah Mumtaz
- Department of Medicine, King Edward Medical University, Lahore, Pakistan
| | | | | | - Giuseppe Derosa
- Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.,Laboratory of Molecular Medicine, University of Pavia, Pavia, Italy
| | - Pamela Maffioli
- Laboratory of Molecular Medicine, University of Pavia, Pavia, Italy
| | | | | | | | - Saeed Khan
- Department of Molecular Pathology, Dow University of Health Sciences, Karachi, Pakistan
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Beyrampour-Basmenj H, Milani M, Ebrahimi-Kalan A, Ben Taleb Z, Ward KD, Dargahi Abbasabad G, Aliyari-serej Z, Ebrahimi Kalan M. An Overview of the Epidemiologic, Diagnostic and Treatment Approaches of COVID-19: What do We Know? Public Health Rev 2021; 42:1604061. [PMID: 34381626 PMCID: PMC8245675 DOI: 10.3389/phrs.2021.1604061] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Accepted: 06/01/2021] [Indexed: 01/08/2023] Open
Abstract
Background: In late December 2019, a new infectious respiratory disease (COVID-19) was reported in a number of patients with a history of exposure to the Huanan seafood market in China. The World Health Organization officially announced the COVID-19 pandemic on March 11, 2020. Here, we provided an overview of the epidemiologic, diagnostic and treatment approaches associated with COVID-19. Methods: We reviewed the publications indexed in major biomedical databases by December 20, 2020 or earlier (updated on May 16, 2021). Search keywords included a combination of: COVID-19, Coronavirus disease 2019, SARS-CoV-2, Epidemiology, Prevention, Diagnosis, Vaccine, and Treatment. We also used available information about COVID-19 from valid sources such as WHO. Results and Conclusion: At the time of writing this review, while most of the countries authorized COVID-19 vaccines for emergency use starting December 8, 2020, there is no a definite cure for it. This review synthesizes current knowledge of virology, epidemiology, clinical symptoms, diagnostic approaches, common treatment strategies, novel potential therapeutic options for control and prevention of COVID-19 infection, available vaccines, public health and clinical implications.
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Affiliation(s)
| | | | | | - Ziyad Ben Taleb
- University of Texas at Arlington, Arlington, VA, United States
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50
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Wuneh A, Kahsay A, Tinsae F, Ashebir F, Giday G, Mirutse G, Gebretsadik G, Gebremedhin G, Weldearegay H, Berhe K, Woldegebriel M, Weldeselassie T, Berhane Y, Hadis Z. Knowledge, Perceptions, Satisfaction, and Readiness of Health-Care Providers Regarding COVID-19 in Northern Ethiopia. J Multidiscip Healthc 2021; 14:1349-1359. [PMID: 34135593 PMCID: PMC8197581 DOI: 10.2147/jmdh.s284106] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2020] [Accepted: 05/17/2021] [Indexed: 12/23/2022] Open
Abstract
Background To protect health-care providers (HCPs) from COVID-19, the WHO recommends applying basic principles of infection prevention and control measures at all health-care facilities. This study aimed to assess the knowledge, perceptions, satisfaction, and readiness of HCPs regarding COVID-19 in Tigrai, Ethiopia in 2020. Methods This cross-sectional study was conducted from June 1 to July, 2020. Data were collected using a self-administered structured questionnaire. Multistage sampling followed by purposive sampling were used to recruit study subjects. SPSS 21 was used to compute proportions and χ2 to identify risk factors. Results Of 765 participants, 88% had adequate knowledge, close to a third showed positive perceptions and were satisfied with their job and nearly a quarter demonstrated readiness to prevent and control COVID-19. Education, knowledge, readiness, perceptions, and job satisfaction with associated with type and readiness of health facilities. Conclusion Despite adequate knowledge of the HCPs about COVID-19, their perceptions and job satisfaction are a concern for the health-care system. Only one in five HCPs was found to be ready to prevent and control COVID-19. Efforts should be exerted to improve perceptions, job satisfaction, and readiness of HCPs to fight COVID-19.
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Affiliation(s)
- Alem Wuneh
- Health System, Mekelle University College of Health Sciences, Mekelle, Tigrai, Ethiopia
| | - Amaha Kahsay
- Nutrition and Dietetics, Mekelle University College of Health Sciences, Mekelle, Tigrai, Ethiopia
| | - Fitiwi Tinsae
- Nursing, Adigrat University College of Health Sciences, Adigrat, Tigrai, Ethiopia
| | - Fisseha Ashebir
- Maternal and Child Health, Tigrai Regional Health Bureau, Mekelle, Tigrai, Ethiopia
| | - Gebreamlak Giday
- Midwifery, Axum University College of Health Sciences, Axum, Tigrai, Ethiopia
| | - Gebremeskel Mirutse
- Environmental and Behavioral Sciences, Mekelle University College of Health Sciences, Mekelle, Tigrai, Ethiopia
| | | | - Getachew Gebremedhin
- Nursing, Adigrat University College of Health Sciences, Adigrat, Tigrai, Ethiopia
| | - Haftom Weldearegay
- Midwifery, Mekelle University College of Health Sciences, Mekelle, Tigrai, Ethiopia
| | - Kalayou Berhe
- Nursing, Mekelle University College of Health Sciences, Mekelle, Tigrai, Ethiopia
| | - Manay Woldegebriel
- Public Health, Axum University College of Health Sciences, Axum, Tigrai, Ethiopia
| | - Tesfay Weldeselassie
- Research Monitoring, Training and Publication, Tigrai Health Research Institute, Mekelle, Tigrai, Ethiopia
| | - Yemane Berhane
- Nursing, Adigrat University College of Health Sciences, Adigrat, Tigrai, Ethiopia
| | - Zinabu Hadis
- Environmental and Behavioral Sciences, Mekelle University College of Health Sciences, Mekelle, Tigrai, Ethiopia
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