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1
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Ortiz-Prado E, Izquierdo-Condoy JS, Vasconez-Gonzalez J, López-Cortés A, Salazar-Santoliva C, Vargas Michay AR, Vélez-Paéz JL, Unigarro L. From pandemic onset to present: five years of insights into ARDS caused by COVID-19. Expert Rev Respir Med 2025:1-20. [PMID: 40372206 DOI: 10.1080/17476348.2025.2507207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2025] [Revised: 04/28/2025] [Accepted: 05/13/2025] [Indexed: 05/16/2025]
Abstract
INTRODUCTION COVID-19-associated acute respiratory distress syndrome (ARDS) has challenged healthcare systems, initially resembling classical ARDS but later recognized as distinct. Unique features such as endothelial injury, microthrombosis, and dysregulated inflammation influenced treatment efficacy. Understanding its evolution is key to optimizing therapy and improving outcomes. AREAS COVERED This review synthesizes current evidence on COVID-19-associated ARDS, covering epidemiology, pathophysiology, clinical phenotypes, and treatments. It explores the shift from L and H phenotypes to a refined disease model and highlights key therapies, including corticosteroids, immunomodulators, prone positioning, ECMO, and vaccination's impact on severity and ARDS incidence. EXPERT OPINION At the onset of the COVID-19 pandemic in December 2019, uncertainty was overwhelming. Early clinical guidelines relied on case reports and small case series, offering only preliminary insights into disease progression and management. Despite the initial chaos, the scientific community launched an unprecedented research effort, with over 11,000 clinical trials registered on ClinicalTrials.gov investigating COVID-19 treatments. Several evidence-based strategies emerged as gold standards for managing COVID-19-associated acute respiratory distress syndrome, surpassing prior approaches. The pandemic exposed vulnerabilities in global healthcare, reshaped modern medicine, accelerated innovation, and reinforced the essential role of evidence-based practice in critical care and public health policy.
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Affiliation(s)
- Esteban Ortiz-Prado
- One Health Research Group, Faculty of Health Science, Universidad de Las Americas, Quito, Ecuador
| | - Juan S Izquierdo-Condoy
- One Health Research Group, Faculty of Health Science, Universidad de Las Americas, Quito, Ecuador
| | - Jorge Vasconez-Gonzalez
- One Health Research Group, Faculty of Health Science, Universidad de Las Americas, Quito, Ecuador
| | - Andrés López-Cortés
- Cancer Research Group (CRG), Faculty of Medicine, Universidad de Las Américas, Quito, Ecuador
| | - Camila Salazar-Santoliva
- One Health Research Group, Faculty of Health Science, Universidad de Las Americas, Quito, Ecuador
| | | | - Jorge Luis Vélez-Paéz
- Universidad Central del Ecuador, Facultad de Ciencias Médicas, Escuela de Medicina, Quito, Ecuador
- Hospital Pablo Arturo Suárez, Unidad de Terapia Intensiva, Centro de Investigación Clínica, Quito, Ecuador
| | - Luis Unigarro
- Department of Intensive Care Unit, Oncologic Hospital SOLCA, Quito, Ecuador
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De Jesús-González LA, León-Juárez M, Lira-Hernández FI, Rivas-Santiago B, Velázquez-Cervantes MA, Méndez-Delgado IM, Macías-Guerrero DI, Hernández-Castillo J, Hernández-Rodríguez X, Calderón-Sandate DN, Mata-Martínez WS, Reyes-Ruíz JM, Osuna-Ramos JF, García-Herrera AC. Advances and Challenges in Antiviral Development for Respiratory Viruses. Pathogens 2024; 14:20. [PMID: 39860981 PMCID: PMC11768830 DOI: 10.3390/pathogens14010020] [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: 11/08/2024] [Revised: 12/26/2024] [Accepted: 12/28/2024] [Indexed: 01/27/2025] Open
Abstract
The development of antivirals for respiratory viruses has advanced markedly in response to the growing threat of pathogens such as Influenzavirus (IAV), respiratory syncytial virus (RSV), and SARS-CoV-2. This article reviews the advances and challenges in this field, highlighting therapeutic strategies that target critical stages of the viral replication cycle, including inhibitors of viral entry, replication, and assembly. In addition, innovative approaches such as inhibiting host cellular proteins to reduce viral resistance and repurposing existing drugs are explored, using advanced bioinformatics tools that optimize the identification of antiviral candidates. The analysis also covers emerging technologies such as nanomedicine and CRISPR gene editing, which promise to improve the stability and efficacy of treatments. While current antivirals offer valuable options, they face challenges such as viral evolution and the need for accessible treatments for vulnerable populations. This article underscores the importance of continued innovation in biotechnology to overcome these limitations and provide safe and effective treatments. Combining traditional and advanced approaches in developing antivirals is essential in order to address respiratory viral diseases that affect global health.
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Affiliation(s)
- Luis Adrián De Jesús-González
- Unidad de Investigación Biomédica de Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas 98000, Mexico; (F.I.L.-H.); (B.R.-S.); (I.M.M.-D.); (D.I.M.-G.); (X.H.-R.); (D.N.C.-S.); (W.S.M.-M.); (A.C.G.-H.)
| | - Moisés León-Juárez
- Laboratorio de Virología Perinatal y Diseño Molecular de Antígenos y Biomarcadores, Departamento de Inmunobioquímica, Instituto Nacional de Perinatología, Ciudad de México 11000, Mexico;
| | - Flor Itzel Lira-Hernández
- Unidad de Investigación Biomédica de Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas 98000, Mexico; (F.I.L.-H.); (B.R.-S.); (I.M.M.-D.); (D.I.M.-G.); (X.H.-R.); (D.N.C.-S.); (W.S.M.-M.); (A.C.G.-H.)
| | - Bruno Rivas-Santiago
- Unidad de Investigación Biomédica de Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas 98000, Mexico; (F.I.L.-H.); (B.R.-S.); (I.M.M.-D.); (D.I.M.-G.); (X.H.-R.); (D.N.C.-S.); (W.S.M.-M.); (A.C.G.-H.)
| | - Manuel Adrián Velázquez-Cervantes
- Laboratorio de Virología Perinatal y Diseño Molecular de Antígenos y Biomarcadores, Departamento de Inmunobioquímica, Instituto Nacional de Perinatología, Ciudad de México 11000, Mexico;
| | - Iridiana Monserrat Méndez-Delgado
- Unidad de Investigación Biomédica de Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas 98000, Mexico; (F.I.L.-H.); (B.R.-S.); (I.M.M.-D.); (D.I.M.-G.); (X.H.-R.); (D.N.C.-S.); (W.S.M.-M.); (A.C.G.-H.)
- Especialidad en Medicina Familiar, Unidad Académica de Medicina Humana y Ciencias de la Salud, Universidad Autónoma de Zacatecas, Zacatecas 98160, Mexico
- Instituto Mexicano del Seguro Social, Unidad de Medicina Familiar # 4, Servicio de Medicina Familiar, Guadalupe, Zacatecas 98618, Mexico
| | - Daniela Itzel Macías-Guerrero
- Unidad de Investigación Biomédica de Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas 98000, Mexico; (F.I.L.-H.); (B.R.-S.); (I.M.M.-D.); (D.I.M.-G.); (X.H.-R.); (D.N.C.-S.); (W.S.M.-M.); (A.C.G.-H.)
- Unidad Académica de Ciencias Químicas, Universidad Autónoma de Zacatecas, Zacatecas 98160, Mexico
| | - Jonathan Hernández-Castillo
- Department of Infectomics and Molecular Pathogenesis, Center for Research and Advanced Studies (CINVESTAV-IPN), Mexico City 07360, Mexico;
| | - Ximena Hernández-Rodríguez
- Unidad de Investigación Biomédica de Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas 98000, Mexico; (F.I.L.-H.); (B.R.-S.); (I.M.M.-D.); (D.I.M.-G.); (X.H.-R.); (D.N.C.-S.); (W.S.M.-M.); (A.C.G.-H.)
- Unidad Académica de Ciencias Químicas, Universidad Autónoma de Zacatecas, Zacatecas 98160, Mexico
| | - Daniela Nahomi Calderón-Sandate
- Unidad de Investigación Biomédica de Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas 98000, Mexico; (F.I.L.-H.); (B.R.-S.); (I.M.M.-D.); (D.I.M.-G.); (X.H.-R.); (D.N.C.-S.); (W.S.M.-M.); (A.C.G.-H.)
- Unidad Académica de Ciencias Químicas, Universidad Autónoma de Zacatecas, Zacatecas 98160, Mexico
| | - Willy Salvador Mata-Martínez
- Unidad de Investigación Biomédica de Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas 98000, Mexico; (F.I.L.-H.); (B.R.-S.); (I.M.M.-D.); (D.I.M.-G.); (X.H.-R.); (D.N.C.-S.); (W.S.M.-M.); (A.C.G.-H.)
- Especialidad en Medicina Familiar, Unidad Académica de Medicina Humana y Ciencias de la Salud, Universidad Autónoma de Zacatecas, Zacatecas 98160, Mexico
- Instituto Mexicano del Seguro Social, Unidad de Medicina Familiar # 4, Servicio de Medicina Familiar, Guadalupe, Zacatecas 98618, Mexico
| | - José Manuel Reyes-Ruíz
- División de Investigación en Salud, Unidad Médica de Alta Especialidad, Hospital de Especialidades No. 14, Centro Médico Nacional “Adolfo Ruiz Cortines”, Instituto Mexicano del Seguro Social (IMSS), Veracruz 91897, Mexico;
- Facultad de Medicina, Región Veracruz, Universidad Veracruzana (UV), Veracruz 91700, Mexico
| | | | - Ana Cristina García-Herrera
- Unidad de Investigación Biomédica de Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas 98000, Mexico; (F.I.L.-H.); (B.R.-S.); (I.M.M.-D.); (D.I.M.-G.); (X.H.-R.); (D.N.C.-S.); (W.S.M.-M.); (A.C.G.-H.)
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de Sousa Pinto M, Fontoura LGO, da Rosa Borges I, Vieira de Melo Bisneto A, Rosa de Oliveira G, Carneiro LC, Chen Chen L, Vieira de Moraes Filho A. Evaluation of infliximab-induced genotoxicity and possible action on BCL-2 and P53 genes. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. PART A 2024; 87:752-761. [PMID: 38922576 DOI: 10.1080/15287394.2024.2368619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/27/2024]
Abstract
Although the last pandemic created an urgency for development of vaccines, there was a continuous and concerted effort to search for therapeutic medications among existing drugs with different indications. One of the medications of interest that underwent this change was infliximab (IFM). This drug is used as an anti-inflammatory, predominantly in patients with Crohn 's disease, colitis ulcerative, and rheumatoid arthritis. In addition to these patients, individuals infected with Coronavirus Disease (COVID-19) were administered this chimeric monoclonal antibody (IMF) to act as an immunomodulator for patients in the absence of comprehensive research. Consequently, the present study aimed to examine the genotoxic effects attributed to IFM treatment employing different assays in vivo using mouse Mus musculus. Therefore, IFM was found to induce genotoxic effects as evidenced by the comet assay but did not demonstrate genotoxic potential utilizing mouse bone marrow MN test. The results of evaluating the expression of the P53 and BCL-2 genes using RT-qPCR showed stimulation of expression of these genes at 24 hr followed by a decline at 48 hr. Although the comet assay provided positive results, it is noteworthy that based upon negative findings in the micronucleus test, the data did not demonstrate significant changes in the genetic material that might affect the therapeutic use of IFM. The stimulation of expression of P53 and BCL-2 genes at 24 hr followed by a decline at 48 hr suggest a transient, if any, effect on genetic material. However, there is still a need for more research to more comprehensively understand the genotoxic profile of this medication.
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Affiliation(s)
- Murillo de Sousa Pinto
- Faculty of Pharmacy, Graduate Program in Health Assistance and Evaluation, Federal University of Goiás, Goiânia, Brazil
- Institute of Health Sciences, Alfredo Nasser University Center, Goiânia, Goiás, Brazil
| | | | | | - Abel Vieira de Melo Bisneto
- Institute of Biological Sciences, Department of Genetics, Laboratory of Radiobiology and Mutagenesis, Federal University of Goiás, Goiânia, Brazil
| | | | - Lílian Carla Carneiro
- Department of Biotechnology, Institute of Tropical Pathology and Public Health, Federal University of Goiás, Goiânia, Goiás, Brazil
| | - Lee Chen Chen
- Institute of Biological Sciences, Department of Genetics, Laboratory of Radiobiology and Mutagenesis, Federal University of Goiás, Goiânia, Brazil
| | - Aroldo Vieira de Moraes Filho
- Faculty of Pharmacy, Graduate Program in Health Assistance and Evaluation, Federal University of Goiás, Goiânia, Brazil
- Institute of Health Sciences, Alfredo Nasser University Center, Goiânia, Goiás, Brazil
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Kim CM, Chung JK, Tamanna S, Bang MS, Tariq M, Lee YM, Seo JW, Kim DY, Yun NR, Seo J, Kim Y, Kim MJ, Kim DM, Cho NH. Comparable Efficacy of Lopinavir/Ritonavir and Remdesivir in Reducing Viral Load and Shedding Duration in Patients with COVID-19. Microorganisms 2024; 12:1696. [PMID: 39203538 PMCID: PMC11357406 DOI: 10.3390/microorganisms12081696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Revised: 08/08/2024] [Accepted: 08/09/2024] [Indexed: 09/03/2024] Open
Abstract
The spread of COVID-19 has significantly increased research on antiviral drugs and measures such as case isolation and contact tracing. This study compared the effects of lopinavir/ritonavir and remdesivir on COVID-19 patients with a control group receiving no antiviral drugs. Patients confirmed to have a SARS-CoV-2 infection via real-time RT-PCR were divided into three groups: lopinavir/ritonavir, remdesivir, and control. We assessed the efficacy of these drugs in reducing viral load and viral shedding duration using real-time RT-PCR and Vero E6 cell cultures. Lopinavir/ritonavir led to no detectable infectious SARS-CoV-2, with a median viral clearance time of one day, whereas one remdesivir-treated case remained culture-positive until day 12. Lopinavir/ritonavir significantly reduced viral load compared to remdesivir and control groups (p = 0.0117 and p = 0.0478). No infectious virus was detected in the lopinavir/ritonavir group, and the non-infectious SARS-CoV-2 proportion remained constant at 90%, higher than in the remdesivir and control groups (p = 0.0097). There was a significant difference in culture positivity among the groups (p = 0.0234), particularly between the lopinavir/ritonavir and remdesivir groups (p = 0.0267). These findings suggest that lopinavir/ritonavir reduces viral load and shortens the viral shedding duration compared to remdesivir, despite not being an effective treatment option.
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Affiliation(s)
- Choon-Mee Kim
- Premedical Science, Chosun University College of Medicine, Gwangju 61452, Republic of Korea
| | - Jae Keun Chung
- Health and Environment Research Institute of Gwangju, Gwangju 61954, Republic of Korea; (J.K.C.)
| | - Sadia Tamanna
- Department of Internal Medicine, Chosun University College of Medicine, Gwangju 61452, Republic of Korea (M.-S.B.)
| | - Mi-Seon Bang
- Department of Internal Medicine, Chosun University College of Medicine, Gwangju 61452, Republic of Korea (M.-S.B.)
| | - Misbah Tariq
- Department of Internal Medicine, Chosun University College of Medicine, Gwangju 61452, Republic of Korea (M.-S.B.)
| | - You Mi Lee
- Department of Internal Medicine, Chosun University College of Medicine, Gwangju 61452, Republic of Korea (M.-S.B.)
| | - Jun-Won Seo
- Department of Internal Medicine, Chosun University College of Medicine, Gwangju 61452, Republic of Korea (M.-S.B.)
| | - Da Young Kim
- Department of Internal Medicine, Chosun University College of Medicine, Gwangju 61452, Republic of Korea (M.-S.B.)
| | - Na Ra Yun
- Department of Internal Medicine, Chosun University College of Medicine, Gwangju 61452, Republic of Korea (M.-S.B.)
| | - Jinjong Seo
- Health and Environment Research Institute of Gwangju, Gwangju 61954, Republic of Korea; (J.K.C.)
| | - Yuri Kim
- Department of Microbiology and Immunology, Seoul National University College of Medicine, 103, Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea
- Institute of Endemic Disease, Seoul National University Medical Research, Seoul 03080, Republic of Korea
| | - Min Ji Kim
- Health and Environment Research Institute of Gwangju, Gwangju 61954, Republic of Korea; (J.K.C.)
| | - Dong-Min Kim
- Department of Internal Medicine, Chosun University College of Medicine, Gwangju 61452, Republic of Korea (M.-S.B.)
| | - Nam-Hyuk Cho
- Department of Microbiology and Immunology, Seoul National University College of Medicine, 103, Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea
- Institute of Endemic Disease, Seoul National University Medical Research, Seoul 03080, Republic of Korea
- Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea
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5
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Obeagu EI, Obeagu GU, Ukibe NR, Oyebadejo SA. Anemia, iron, and HIV: decoding the interconnected pathways: A review. Medicine (Baltimore) 2024; 103:e36937. [PMID: 38215133 PMCID: PMC10783375 DOI: 10.1097/md.0000000000036937] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2023] [Accepted: 12/20/2023] [Indexed: 01/14/2024] Open
Abstract
This review delves into the intricate relationship between anemia, iron metabolism, and human immunodeficiency virus (HIV), aiming to unravel the interconnected pathways that contribute to the complex interplay between these 3 entities. A systematic exploration of relevant literature was conducted, encompassing studies examining the association between anemia, iron status, and HIV infection. Both clinical and preclinical investigations were analyzed to elucidate the underlying mechanisms linking these components. Chronic inflammation, a hallmark of HIV infection, disrupts iron homeostasis, impacting erythropoiesis and contributing to anemia. Direct viral effects on bone marrow function further compound red blood cell deficiencies. Antiretroviral therapy, while essential for managing HIV, introduces potential complications, including medication-induced anemia. Dysregulation of iron levels in different tissues adds complexity to the intricate network of interactions. Effective management of anemia in HIV necessitates a multifaceted approach. Optimization of antiretroviral therapy, treatment of opportunistic infections, and targeted nutritional interventions, including iron supplementation, are integral components. However, challenges persist in understanding the specific molecular mechanisms governing these interconnected pathways. Decoding the interconnected pathways of anemia, iron metabolism, and HIV is imperative for enhancing the holistic care of individuals with HIV/AIDS. A nuanced understanding of these relationships will inform the development of more precise interventions, optimizing the management of anemia in this population. Future research endeavors should focus on elucidating the intricate molecular mechanisms, paving the way for innovative therapeutic strategies in the context of HIV-associated anemia.
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Affiliation(s)
| | | | - Nkiruka Rose Ukibe
- Department of Medical Laboratory Science, Nnamdi Azikiwe University, Nnewi, Anambra State, Nigeria
| | - Samson Adewale Oyebadejo
- Department of Biomedical Laboratory Sciences, Faculty of Fundamental Applied Sciences, Institut d’ Enseignement Superiuor de Ruhengeri (INES-RUHENGERI), Musanze District, Northern Region, Rwanda
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Lopez-Herguedas N, Irazola M, Alvarez-Mora I, Orive G, Lertxundi U, Olivares M, Zuloaga O, Prieto A. Comprehensive micropollutant characterization of wastewater during Covid-19 crisis in 2020: Suspect screening and environmental risk prioritization strategy. THE SCIENCE OF THE TOTAL ENVIRONMENT 2023; 873:162281. [PMID: 36822422 PMCID: PMC9943555 DOI: 10.1016/j.scitotenv.2023.162281] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 02/10/2023] [Accepted: 02/12/2023] [Indexed: 06/04/2023]
Abstract
Micropollutants monitoring in wastewater can serve as a picture of what is consuming society and how it can impact the aquatic environment. In this work, a suspect screening approach was used to detect the known and unknown contaminants in wastewater samples collected from two wastewater treatment plants (WWTPs) located in the Basque Country (Crispijana in Alava, and Galindo in Vizcaya) during two weekly sampling campaigns, which included the months from April to July 2020, part of the confinement period caused by COVID-19. To that aim, high-resolution mass spectrometry was used to collect full-scan data-dependent tandem mass spectra from the water samples using a suspect database containing >40,000 chemical substances. The presence of > 80 contaminants was confirmed (level 1) and quantified in both WWTP samples, while at least 47 compounds were tentatively identified (2a). Among the contaminants of concern, an increase in the occurrence of some compounds used for COVID-19 disease treatment, such as lopinavir and hydroxychloroquine, was observed during the lockdown. A prioritization strategy for environmental risk assessment was carried out considering only the compounds quantified in the effluents of Crispijana and Galindo WWTPs. The compounds were scored based on the removal efficiency, estimated persistency, bioconcentration factor, mobility, toxicity potential and frequency of detection in the samples. With this approach, 33 compounds (e.g. amantadine, clozapine or lopinavir) were found to be considered key contaminants in the analyzed samples based on their concentration, occurrence and potential toxicity. Additionally, antimicrobial (RQ-AR) and antiviral (EDRP) risk of certain compounds was evaluated, where ciprofloxacin and fluconazole represented medium risk for antibiotic resistance (1 > RQ-AR > 0.1) in the aquatic ecosystems. Regarding mixture toxicity, the computed sum of toxic unit values of the different effluents (> 1) suggest that interactions between the compounds need to be considered for future environmental risk assessments.
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Affiliation(s)
- N Lopez-Herguedas
- Department of Analytical Chemistry, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Leioa, Basque Country, Spain; Research Centre for Experimental Marine Biology and Biotechnology (PIE), University of the Basque Country (UPV/EHU), Plentzia, Basque Country, Spain.
| | - M Irazola
- Department of Analytical Chemistry, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Leioa, Basque Country, Spain; Research Centre for Experimental Marine Biology and Biotechnology (PIE), University of the Basque Country (UPV/EHU), Plentzia, Basque Country, Spain
| | - I Alvarez-Mora
- Department of Analytical Chemistry, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Leioa, Basque Country, Spain; Research Centre for Experimental Marine Biology and Biotechnology (PIE), University of the Basque Country (UPV/EHU), Plentzia, Basque Country, Spain
| | - G Orive
- NanoBioCel Group, Laboratory of Pharmaceutics, Faculty of Pharmacy, University of the Basque Country UPV/EHU, Paseo de la Universidad 7, Vitoria-Gasteiz 01006, Spain; Bioaraba, NanoBioCel Research Group, 01009 Vitoria-Gasteiz, Spain
| | - U Lertxundi
- Bioaraba, NanoBioCel Research Group, 01009 Vitoria-Gasteiz, Spain; Bioaraba Health Research Institute; Osakidetza Basque Health Service, Araba Mental Health Network, Araba Psychiatric Hospital, Pharmacy Service, c/Alava 43, 01006 Vitoria-Gasteiz, Alava, Spain
| | - M Olivares
- Department of Analytical Chemistry, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Leioa, Basque Country, Spain; Research Centre for Experimental Marine Biology and Biotechnology (PIE), University of the Basque Country (UPV/EHU), Plentzia, Basque Country, Spain
| | - O Zuloaga
- Department of Analytical Chemistry, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Leioa, Basque Country, Spain; Research Centre for Experimental Marine Biology and Biotechnology (PIE), University of the Basque Country (UPV/EHU), Plentzia, Basque Country, Spain
| | - A Prieto
- Department of Analytical Chemistry, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Leioa, Basque Country, Spain; Research Centre for Experimental Marine Biology and Biotechnology (PIE), University of the Basque Country (UPV/EHU), Plentzia, Basque Country, Spain
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7
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Venturas JP. HIV and COVID-19 Disease. Semin Respir Crit Care Med 2023; 44:35-49. [PMID: 36646084 DOI: 10.1055/s-0042-1758852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Despite effective antiretroviral therapy (ART), HIV infected individuals throughout the world remain at significant risk of respiratory infections and non-communicable disease. Severe disease from SARS-CoV-2 is associated with a hyperinflammatory phenotype which manifests in the lungs as pneumonia and in some cases can lead to acute respiratory failure. Progression to severe COVID-19 is associated with comorbid disease such as obesity, diabetes mellitus and cardiovascular disease, however data concerning the associated risks of HIV coinfection are still conflicting, with large population studies demonstrating poorer outcomes, whilst smaller, case-controlled studies showing better outcomes. Furthermore, underlying immunopathological processes within the lungs and elsewhere, including interactions with other opportunistic infections (OI), remain largely undefined. Nonetheless, new and repurposed anti-viral therapies and vaccines which have been developed are safe to use in this population, and anti-inflammatory agents are recommended with the caveat that the coexistence of opportunistic infections is considered and excluded. Finally, HIV infected patients remain reliant on good ART adherence practices to maintain HIV viral suppression, and some of these practices were disrupted during the COVID-19 pandemic, putting these patients at further risk for acute and long-term adverse outcomes.
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Affiliation(s)
- Jacqui P Venturas
- Department of Internal Medicine and Pulmonology, Charlotte Maxeke Johannesburg Academic Hospital and Universtity of the Witwatersrand, Johannesburg, South Africa
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Al-Rawi TSS, Al-Ani RM. Liver dysfunction-related COVID-19: A narrative review. World J Meta-Anal 2023; 11:5-17. [DOI: 10.13105/wjma.v11.i1.5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Revised: 11/25/2022] [Accepted: 12/14/2022] [Indexed: 01/11/2023] Open
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Li X, Wang W, Yan S, Zhao W, Xiong H, Bao C, Chen J, Yue Y, Su Y, Zhang C. Drug-induced liver injury in COVID-19 treatment: Incidence, mechanisms and clinical management. Front Pharmacol 2022; 13:1019487. [PMID: 36518661 PMCID: PMC9742434 DOI: 10.3389/fphar.2022.1019487] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Accepted: 11/14/2022] [Indexed: 07/21/2023] Open
Abstract
The COVID-19 outbreak triggered a serious and potentially lethal pandemic, resulting in massive health and economic losses worldwide. The most common clinical manifestations of COVID-19 patients are pneumonia and acute respiratory distress syndrome, with a variety of complications. Multiple organ failure and damage, ultimately leading to patient death, are possible as a result of medication combinations, and this is exemplified by DILI. We hope to summarize DILI caused by the antiviral drugs favipiravir, remdesivir, lopinavir/ritonavir, and hydroxychloroquine in COVID-19 patients in this review. The incidence of liver injury in the treatment of COVID-19 patients was searched on PubMed to investigate DILI cases. The cumulative prevalence of acute liver injury was 23.7% (16.1%-33.1%). We discuss the frequency of these events, potential mechanisms, and new insights into surveillance strategies. Furthermore, we also describe medication recommendations aimed at preserving DILI caused by treatment in COVID-19 patients.
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Affiliation(s)
- Xichuan Li
- Tianjin Key Laboratory of Animal and Plant Resistance, College of Life Sciences, Tianjin Normal University, Tianjin, China
| | - Wanting Wang
- Department of Colorectal Surgery, Tianjin Institute of Coloproctology, The Institute of Translational Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, China
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Suying Yan
- Department of Colorectal Surgery, Tianjin Institute of Coloproctology, The Institute of Translational Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, China
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Weipeng Zhao
- Department of Breast Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China
| | - Hui Xiong
- School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China
| | - Cuiping Bao
- Departments of Radiology, Tianjin Union Medical Center, Tianjin, China
| | - Jinqian Chen
- Departments of Pharmacy, NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital, Tianjin, China
| | - Yuan Yue
- Tianjin Key Laboratory of Animal and Plant Resistance, College of Life Sciences, Tianjin Normal University, Tianjin, China
| | - Yanjun Su
- Department of Lung Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China
| | - Chunze Zhang
- Department of Colorectal Surgery, Tianjin Institute of Coloproctology, The Institute of Translational Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, China
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10
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Ruggiero R, Balzano N, Di Napoli R, Sullo MG, Rossi F, Capuano A, Rafaniello C. Utilizing clinical pharmacology in the drug repurposing arena: a look into COVID-19. Expert Rev Clin Pharmacol 2022; 15:1225-1231. [PMID: 36196903 DOI: 10.1080/17512433.2022.2132226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
INTRODUCTION Drug repurposing represented an important contribution in the management of COVID-19, becoming the first line of defense to mitigate the effects of the new coronavirus. In a brief time, drug repurposing (DR) provided potentially effective and already available drugs for COVID-19, while specific therapies against SARS-CoV-2 and/or vaccines were developing. Identifying repurposed drugs requires a multidisciplinary approach, where clinical pharmacology represents the missing piece of the puzzle. AREAS COVERED Nowadays, clinical pharmacology is recognized as a discipline at the core of translational science, whose activities lead to the identification of the right drug for the right patient. In the context of the COVID-19 pandemic, its role in drug development and therapy choice has been decisive and itself repositioned. In this review, we tried to highlight the important role of clinical pharmacology in the identification and evaluation of possible repurposed drugs for COVID-19. EXPERT OPINION We believe that clinical pharmacology had an important role in identifying patient-oriented therapy during the COVID-19 pandemic. In this context, DR was just one of the challenges for clinical pharmacology, which proved that this discipline is ready to respond to future threats.
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Affiliation(s)
- Rosanna Ruggiero
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Department of Experimental Medicine, Section of Pharmacology "L. Donatelli," University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Nunzia Balzano
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Department of Experimental Medicine, Section of Pharmacology "L. Donatelli," University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Raffaella Di Napoli
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Department of Experimental Medicine, Section of Pharmacology "L. Donatelli," University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Maria Giuseppa Sullo
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Department of Experimental Medicine, Section of Pharmacology "L. Donatelli," University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Francesco Rossi
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Department of Experimental Medicine, Section of Pharmacology "L. Donatelli," University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Annalisa Capuano
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Department of Experimental Medicine, Section of Pharmacology "L. Donatelli," University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Concetta Rafaniello
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Department of Experimental Medicine, Section of Pharmacology "L. Donatelli," University of Campania "Luigi Vanvitelli", Naples, Italy
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11
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Nimitvilai S, Suputtamongkol Y, Poolvivatchaikarn U, Rassamekulthana D, Rongkiettechakorn N, Mungaomklang A, Assanasaen S, Wongsawat E, Boonarkart C, Sawaengdee W. A Randomized Controlled Trial of Combined Ivermectin and Zinc Sulfate versus Combined Hydroxychloroquine, Darunavir/Ritonavir, and Zinc Sulfate among Adult Patients with Asymptomatic or Mild Coronavirus-19 Infection. J Glob Infect Dis 2022; 14:69-74. [PMID: 35910820 PMCID: PMC9336605 DOI: 10.4103/jgid.jgid_281_21] [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: 10/17/2021] [Revised: 02/14/2022] [Accepted: 04/08/2022] [Indexed: 11/29/2022] Open
Abstract
Introduction: Ivermectin, hydroxychloroquine (HQ), and darunavir/ritonavir are widely prescribed as an oral treatment for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection despite their uncertainty of clinical benefit. The objective is to determine the safety and the efficacies of two treatment regimens against SARS-CoV-2 infection. Methods: We conducted an open-labeled, randomized, controlled trial to compare the efficacy between a 3-day course of once-daily high-dose oral ivermectin plus zinc sulfate (Group A) and a combination of HQ, darunavir/ritonavir, and zinc sulfate (HQ + antiretroviral, Group B) for 5 days in asymptomatic or mild SARS-CoV-2 infection. The study period was between December 2020 and April 2021. Results: Overall, 113 patients were randomized and analyzed (57 patients in Group A and 56 patients in Group B). The median duration to achieve the virological outcome of either undetected or cycle threshold (Ct) for N gene of SARS-CoV-2 by real-time polymerase chain reaction was 6 days (95% confidence interval [CI] 5.3–6.7) versus 7 days (95% CI: 5.4–8.6) in Group A and Group B, respectively (P = 0.419) in the modified intention-to-treat population. All patients were discharged from hospital quarantine as planned. Two patients in Group A and one patient in Group B were considered clinically worsening and received 10 days of favipiravir treatment. There was no serious adverse event found in both groups. Conclusion: We demonstrated that both treatment regimens were safe, but both treatment regimens had no virological or clinical benefit. Based on this result and current data, there is no supporting evidence for the clinical benefit of ivermectin for coronavirus-19.
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Affiliation(s)
| | - Yupin Suputtamongkol
- Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | | | | | | | - Anek Mungaomklang
- Office of Disease Prevention and Control Region 4 Saraburi, Ministry of Public Health, Bangkok, Thailand
| | - Susan Assanasaen
- Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Ekkarat Wongsawat
- Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Chompunuch Boonarkart
- Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Waritta Sawaengdee
- Department of Medical Sciences, Genomic Medicine and Innovation Support, Ministry of Public Health, Nonthaburi, Thailand
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12
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Significance of Immune Status of SARS-CoV-2 Infected Patients in Determining the Efficacy of Therapeutic Interventions. J Pers Med 2022; 12:jpm12030349. [PMID: 35330349 PMCID: PMC8955701 DOI: 10.3390/jpm12030349] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2021] [Revised: 02/12/2022] [Accepted: 02/14/2022] [Indexed: 12/15/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19) is now being investigated for its distinctive patterns in the course of disease development which can be indicated with miscellaneous immune responses in infected individuals. Besides this series of investigations on the pathophysiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), significant fundamental immunological and physiological processes are indispensable to address clinical markers of COVID-19 disease and essential to identify or design effective therapeutics. Recent developments in the literature suggest that deficiency of type I interferon (IFN) in serum samples can be used to represent a severe progression of COVID-19 disease and can be used as the basis to develop combined immunotherapeutic strategies. Precise control over inflammatory response is a significant aspect of targeting viral infections. This account presents a brief review of the pathophysiological characteristics of the SARS-CoV-2 virus and the understanding of the immune status of infected patients. We further discuss the immune system’s interaction with the SARS-CoV-2 virus and their subsequent involvement of dysfunctional immune responses during the progression of the disease. Finally, we highlight some of the implications of the different approaches applicable in developing promising therapeutic interventions that redirect immunoregulation and viral infection.
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13
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Monroe I, Dale M, Schwabe M, Schenkel R, Schenarts PJ. The COVID-19 Patient in the Surgical Intensive Care Unit. Surg Clin North Am 2022; 102:1-21. [PMID: 34800379 PMCID: PMC8479422 DOI: 10.1016/j.suc.2021.09.015] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/09/2023]
Abstract
COVID-19 continues to rampage around the world. Noncritical care-trained physicians may be deployed into the intensive care unit to manage these complex patients. Although COVID-19 is primarily a respiratory disease, it is also associated with significant pathology in the brain, heart, vasculature, lungs, gastrointestinal tract, and kidneys. This article provides an overview of COVID-19 using an organ-based, systematic approach.
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14
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Xu X, Yue L, Li B, Liu Y, Wang Y, Zhang W, Wang L. DSGAT: predicting frequencies of drug side effects by graph attention networks. Brief Bioinform 2022; 23:6511198. [DOI: 10.1093/bib/bbab586] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Revised: 12/01/2021] [Accepted: 12/20/2021] [Indexed: 12/22/2022] Open
Abstract
Abstract
A critical issue of drug risk–benefit evaluation is to determine the frequencies of drug side effects. Randomized controlled trail is the conventional method for obtaining the frequencies of side effects, while it is laborious and slow. Therefore, it is necessary to guide the trail by computational methods. Existing methods for predicting the frequencies of drug side effects focus on modeling drug–side effect interaction graph. The inherent disadvantage of these approaches is that their performance is closely linked to the density of interactions but which is highly sparse. More importantly, for a cold start drug that does not appear in the training data, such methods cannot learn the preference embedding of the drug because there is no link to the drug in the interaction graph. In this work, we propose a new method for predicting the frequencies of drug side effects, DSGAT, by using the drug molecular graph instead of the commonly used interaction graph. This leads to the ability to learn embeddings for cold start drugs with graph attention networks. The proposed novel loss function, i.e. weighted $\varepsilon$-insensitive loss function, could alleviate the sparsity problem. Experimental results on one benchmark dataset demonstrate that DSGAT yields significant improvement for cold start drugs and outperforms the state-of-the-art performance in the warm start scenario. Source code and datasets are available at https://github.com/xxy45/DSGAT.
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15
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Middha SK, David A, Haldar S, Boro H, Panda P, Bajare N, Milesh L, Devaraj V, Usha T. Databases, DrugBank, and virtual screening platforms for therapeutic development. COMPUTATIONAL APPROACHES FOR NOVEL THERAPEUTIC AND DIAGNOSTIC DESIGNING TO MITIGATE SARS-COV-2 INFECTION 2022. [PMCID: PMC9300480 DOI: 10.1016/b978-0-323-91172-6.00021-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
The upsurge of the severe acute respiratory syndrome-Coronavirus-2 (SARS-CoV-2) has turned into a global health disaster. Many remodeled medications were suggested for treatment in the early stages of this pandemic, but these dosages afterward came across with distinct offshoots. Thus, these consequences compelled the scientists to develop new drugs using various antiviral, antiinflammatory, antibacterial, and phytochemical compounds. A handful of drugs have been scrutinized in silico, in vitro, plus through human trials such as anti-SARS-CoV-2 agents and made available as various databases by various scientific communities. The SARS-CoV-2 pandemic databases are designed to allay difficulties associated with this scenario. Some of the popular databases are GESS (global evaluation of SARS-CoV-2/HCoV-19 sequences) which gives a thorough study of data based on tenfold of thousands of complete coverage and quality of SARS-CoV-2 genomes, CORona Drug InTERactions (CORDITE) database for SARS-CoV-2 which profoundly combines the understanding of potential drugs and make it available for scientists and medicos. SARSCOVIDB set one’s sights to merge all differential gene expression data, at mRNA and protein levels, helping to accelerate analysis and research on the molecular impact of covid-19. This chapter aims to provide a piece of complete information about the SARS-CoV-2 virus databases, potentially available drugs, and virtual screening methods. And also provides a different webserver to reach out for information related to the COVID-19 pandemic and its future.
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16
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Mousavi SA, Heydari K, Mehravaran H, Saeedi M, Alizadeh‐Navaei R, Hedayatizadeh‐Omran A, Shamshirian A. Melatonin effects on sleep quality and outcomes of COVID-19 patients: An open-label, randomized, controlled trial. J Med Virol 2022; 94:263-271. [PMID: 34460132 PMCID: PMC8662261 DOI: 10.1002/jmv.27312] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 08/25/2021] [Accepted: 08/27/2021] [Indexed: 02/05/2023]
Abstract
This trial aims to evaluate the effectiveness of adding melatonin to the treatment protocol of hospitalized coronavirus disease 2019 (COVID-19) patients. This was an open-label, randomized controlled clinical trial in hospitalized COVID-19 patients. Patients were randomized into a treatment arm receiving melatonin plus standard care or a control arm receiving standard care alone. The trial's primary endpoint was sleep quality examined by the Leeds Sleep Evaluation Questionnaire (LSEQ). The trial's secondary endpoints were symptoms alleviation by Day 7, intensive care unit admission, 10-day mortality, white blood cell count, lymphocyte count, C-reactive protein status, and peripheral capillary oxygen saturation. Ninety-six patients were recruited and allocated to either the melatonin arm (n = 48) or control arm (n = 48). Baseline characteristics were similar across treatment arms. There was no significant difference in symptoms on Day 7. The mean of the LSEQ scores was significantly higher in the melatonin group (p < 0.001). There was no significant difference in laboratory data, except for blood oxygen saturation, which has improved significantly in the melatonin group compared with the control group (95.81% vs. 93.65% respectively, p = 0.003). This clinical trial study showed that the combination of oral melatonin tablets and standard treatment could substantially improve sleep quality and blood oxygen saturation in hospitalized COVID-19 patients.
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Affiliation(s)
- Seyed Abbas Mousavi
- Department of Psychiatry, Psychiatry and Behavioral Sciences Research Center, Addiction InstituteMazandaran University of Medical SciencesSariIran
| | - Keyvan Heydari
- Gastrointestinal Cancer Research Center, Non‐Communicable Diseases InstituteMazandaran University of Medical SciencesSariIran
- Student Research Committee, School of MedicineMazandaran University of Medical SciencesRamsarIran
| | - Hossein Mehravaran
- Division of Pulmonary and Critical Care, Department of Internal Medicine, School of MedicineMazandaran University of Medical SciencesSariIran
| | - Majid Saeedi
- Pharmaceutical Sciences Research CenterMazandaran University of Medical SciencesSariIran
| | - Reza Alizadeh‐Navaei
- Gastrointestinal Cancer Research Center, Non‐Communicable Diseases InstituteMazandaran University of Medical SciencesSariIran
| | - Akbar Hedayatizadeh‐Omran
- Gastrointestinal Cancer Research Center, Non‐Communicable Diseases InstituteMazandaran University of Medical SciencesSariIran
| | - Amir Shamshirian
- Gastrointestinal Cancer Research Center, Non‐Communicable Diseases InstituteMazandaran University of Medical SciencesSariIran
- Department of Medical Laboratory Sciences, Student Research Committee, School of Allied Medical ScienceMazandaran University of Medical SciencesSariIran
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17
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Mittal N, Mittal R. Repurposing old molecules for new indications: Defining pillars of success from lessons in the past. Eur J Pharmacol 2021; 912:174569. [PMID: 34653378 DOI: 10.1016/j.ejphar.2021.174569] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 08/30/2021] [Accepted: 10/11/2021] [Indexed: 02/06/2023]
Abstract
Drug repurposing or studying existing drugs for potential therapeutic utility in newer indications has been identified as an attractive option for treating a number of diseases. Various strategies of drug repurposing include serendipitous observation of drug's unexpected effects, directing the failed investigational drugs to new indications and currently adopted systematic approach to identify, screen and develop existing drug molecules for new off-label indications. Drug repurposing is able to constructively overcome the bottleneck restraints encountered during traditional de novo drug development process in grounds of timelines, cost and resources. However, success rates of drug repurposing programs are not very impressive. Through a meticulous examination of some failed repurposing attempts we aimed to identify key factors leading to high attrition rate in such studies. Based on the fundamental elements of knowledge and evaluation, we have defined four pillars toward improving success rate in drug repurposing programs viz. sound knowledge of the repurposed drug's pharmacological characteristics (pillar 1: drug pharmacology); drug formulation considerations in new indication (pillar 2: drug formulation); evaluation in representative biological assays with translational potential (pillar 3: evaluation in biological assays); and robust clinical trial methodologies including biomarker driven approach to provide conclusive evidence of repurposed drug's efficacy in new indication (pillar 4: clinical evaluation). In addition to the pharmacological challenges, certain regulatory concerns, including lack of clear guidelines for evaluation and market exclusivity pose hurdles in the application of drug repurposing, which may however be overcome to a great extent by adopting some strategies as discussed in this review.
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Affiliation(s)
- Niti Mittal
- Dept. of Pharmacology, Postgraduate Institute of Medical Sciences, Rohtak, 124001, India.
| | - Rakesh Mittal
- Dept. of Pharmacology, Postgraduate Institute of Medical Sciences, Rohtak, 124001, India
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18
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Ries MD. CORR Insights®: THAs Performed Within 6 Months of Clostridioides difficile Infection Are Associated with Increased Risk of 90-day Complications. Clin Orthop Relat Res 2021; 479:2712-2713. [PMID: 34280173 PMCID: PMC8726556 DOI: 10.1097/corr.0000000000001898] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 06/23/2021] [Indexed: 01/31/2023]
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19
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Wadaa-Allah A, Emhamed MS, Sadeq MA, Ben Hadj Dahman N, Ullah I, Farrag NS, Negida A. Efficacy of the current investigational drugs for the treatment of COVID-19: a scoping review. Ann Med 2021; 53:318-334. [PMID: 33706639 PMCID: PMC7971293 DOI: 10.1080/07853890.2021.1875500] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Accepted: 01/08/2021] [Indexed: 01/08/2023] Open
Abstract
To date, there is no final FDA-approved treatment for COVID-19. There are thousands of studies published on the available treatments for COVID-19 virus in the past year. Therefore, it is crucial to synthesize and summarize the evidence from published studies on the safety and efficacy of experimental treatments of COVID-19. We conducted a systematic literature search of MEDLINE, PubMed, Cochrane Library, GHL, OpenGrey, ICTRP, and ClinicalTrials.gov databases through April 2020. We obtained 2699 studies from the initial literature search. Of them, we included 28 eligible studies that met our eligibility criteria. The sample size of the included studies is 2079 individuals. We extracted and pooled the available data and conducted a quality assessment for the eligible studies. From the 28 studies, only 13 studies provide strong evidence. Our results showed that Favipiravir and Hydroxycholoroquine shorten viral clearance and clinical recovery time and promote pneumonia absorption. On the other hand, Lopinavir-ritonavir either alone or combined with arbidol or interferons has no significant difference superior to the standard care. Corticosteroids, Convalescent plasma transfusion, and anticoagulant therapies provide a better prognosis. Remedsivir, Tocilizumab, Immunoglobulin, Mesenchymal stem cell transplantation showed effective treatment results, but further confirmatory studies are needed. In conclusion, Favipiravir and Remedsivir might be promising drugs in the treatment of COVID-19 patients. .
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Affiliation(s)
- Ahmed Wadaa-Allah
- Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt
| | | | | | | | - Irfan Ullah
- Kabir Medical College, Gandhara University, Peshawar, Pakistan
| | - Nesrine S. Farrag
- Community Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Ahmed Negida
- Zagazig University Hospitals, Zagazig University, El-Sharkia, Egypt
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20
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Song JE, Kang MK, Lee YR, Lee CH, Park JG, Kweon YO, Tak WY, Park SY, Jang SY, Hwang JS, Jang BK, Jang WY, Suh JI, Chung WJ, Kim BS. Multicenter Analysis of Clinical Features and Prognosis of COVID-19 Patients with Hepatic Impairment. Gut Liver 2021; 15:606-615. [PMID: 33782216 PMCID: PMC8283294 DOI: 10.5009/gnl20267] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2020] [Revised: 01/05/2021] [Accepted: 01/06/2021] [Indexed: 01/08/2023] Open
Abstract
Background/Aims Recent data indicate the presence of liver enzyme abnormalities in patients with coronavirus disease 2019 (COVID-19). We aimed to evaluate the clinical features and treatment outcomes of COVID-19 patients with abnormal liver enzymes. Methods We performed a retrospective, multicenter study of 874 COVID-19 patients admitted to five tertiary hospitals from February 20 to April 14, 2020. Data on clinical features, laboratory parameters, medications, and treatment outcomes were collected until April 30, 2020, and compared between patients with normal and abnormal aminotransferases. Results Abnormal aminotransferase levels were observed in 362 patients (41.1%), of which 94 out of 130 (72.3%) and 268 out of 744 (36.0%) belonged to the severe and non-severe COVID- 19 categories, respectively. The odds ratios (95% confidence interval) for male patients, patients with a higher body mass index, patients with severe COVID-19 status, and patients with lower platelet counts were 1.500 (1.029 to 2.184, p=0.035), 1.097 (1.012 to 1.189, p=0.024), 2.377 (1.458 to 3.875, p=0.001), and 0.995 (0.993 to 0.998, p>0.001), respectively, indicating an independent association of these variables with elevated aminotransferase levels. Lopinavir/ ritonavir and antibiotic use increased the odds ratio of abnormal aminotransferase levels after admission (1.832 and 2.646, respectively, both p<0.05). The median time to release from quarantine was longer (22 days vs 26 days, p=0.001) and the mortality rate was higher (13.0% vs 2.9%, p<0.001) in patients with abnormal aminotransferase levels. Conclusions Abnormal aminotransferase levels are common in COVID-19 patients and are associated with poor clinical outcomes. Multivariate analysis of patients with normal aminotransferase levels on admission showed that the use of lopinavir/ritonavir and antibiotics was associated with abnormal aminotransferase levels; thus, careful monitoring is needed.
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Affiliation(s)
- Jeong Eun Song
- Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea
| | - Min Kyu Kang
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
| | - Yu Rim Lee
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Chang Hyeong Lee
- Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea
| | - Jung Gil Park
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
| | - Young Oh Kweon
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Won Young Tak
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Soo Young Park
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Se Young Jang
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Jae Seok Hwang
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Byoung Kuk Jang
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Won Young Jang
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Jeong Ill Suh
- Department of Internal Medicine, Dongguk University College of Medicine, Gyeongju, Korea
| | - Woo Jin Chung
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Byung Seok Kim
- Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea
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21
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Tang H, Zhou L, Li X, Kinlaw AC, Yang JY, Moon AM, Barnes EL, Wang T. Drug-induced liver injury associated with lopinavir-ritonavir in patients with COVID-19: a disproportionality analysis of U.S. food and drug administration adverse event reporting system (FAERS) data. Int J Clin Pharm 2021; 43:1116-1122. [PMID: 34328585 PMCID: PMC8323539 DOI: 10.1007/s11096-021-01311-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Accepted: 07/21/2021] [Indexed: 02/06/2023]
Abstract
Background Liver injury has been documented independently in novel coronavirus disease 2019 (COVID-19) patients and patients treated with lopinavir-ritonavir. Objective to investigate the drug-induced liver injury associated with lopinavir-ritonavir among the patients with COVID-19. Methods We conducted a disproportionality analysis of US Food and Drug Administration Adverse Event Reporting System (FAERS) between 2020Q1 and 2021Q1 to evaluate the association between lopinavir-ritonavir and risk of drug-induced liver injury (or severe drug-induced liver injury) and calculated their reporting odds ratios (RORs) with 95% confidence intervals (CIs). Results A total of 3,425 cases of drug-induced liver injury were reported in 19,782 patients with COVID-19. The ROR for drug-induced liver injury was 2.99 (2.59-3.46), 3.16 (2.68-3.73), and 5.39 (4.63-6.26) when comparing lopinavir-ritonavir with all other drugs, hydroxychloroquine/chloroquine only, and remdesivir, respectively. For severe drug-induced liver injury, RORs for lopinavir-ritonavir provided evidence of an association compared with all other drugs (3.98; 3.15-5.05), compared with hydroxychloroquine/chloroquine only (5.33; 4.09-6.94), and compared with remdesivir (3.85; 3.03-4.89). Conclusions In the FAERS, we observed a disproportional signal for drug-induced liver injury associated with lopinavir-ritonavir in patients with COVID-19.
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Affiliation(s)
- Huilin Tang
- Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, FL, USA.
| | - Liyuan Zhou
- Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina At Chapel Hill, Chapel Hill, NC, USA
| | - Xiaotong Li
- Institute for Drug Evaluation, Peking University Health Science Center, Beijing, China
| | - Alan C Kinlaw
- Division of Pharmaceutical Outcome and Policy, University of North Carolina School of Pharmacy, Chapel Hill, NC, USA
- Cecil G. Sheps Center for Health Services Research, University of North Carolina At Chapel Hill, Chapel Hill, NC, USA
| | - Jeff Y Yang
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina At Chapel Hill, Chapel Hill, NC, USA
| | - Andrew M Moon
- Center for Gastrointestinal Biology and Disease, School of Medicine, University of North Carolina At Chapel Hill, Chapel Hill, NC, USA
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina At Chapel Hill, Chapel Hill, NC, USA
| | - Edward L Barnes
- Center for Gastrointestinal Biology and Disease, School of Medicine, University of North Carolina At Chapel Hill, Chapel Hill, NC, USA
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina At Chapel Hill, Chapel Hill, NC, USA
| | - Tiansheng Wang
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina At Chapel Hill, Chapel Hill, NC, USA
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22
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Karahalil B, Elkama A. COVID-19: Are Experimental Drugs Cure or Ill? Curr Drug Saf 2021; 17:83-89. [PMID: 34315382 DOI: 10.2174/1574886316666210727150127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Revised: 12/17/2020] [Accepted: 04/16/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) is a new strain of coronavirus. It is characterized by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has quickly influenced all over the world since it spreads easily. Common symptoms are fever, cough, difficulty in breathing and muscle aches. Despite the urgent need to find an effective antiviral treatment, already available agents are being used alone or in combination all over the world. At the beginning of the pandemic, death rates of infection caused by COVID-19 are high but "is COVID-19 responsible for all deaths?", or "are there any contributions of the frequently used drugs in this period to these deaths?" Surely herd immunity plays a major role and has the contribution in the decline in mortality rates. Meanwhile, it is kept in mind that due to safety concerns, changes have also been made to the dosage and combined use of frequently used drugs. OBJECTIVE In this review, answers to two questions above and the safety of treatments, toxicities of agents involving chloroquine, hydroxychloroquine, remdesivir, favipiravir, lopiravir/ritonavir, sarilumab, tocilizumab, siltuximab, corticosteroids and bromhexine which are the most frequently used in both Turkey and all over the world will be summarized. CONCLUSION Among these drugs favipiravir seems the most promising drug due to more tolerable adverse effects. More clinical trials with large sample sizes are needed to find the most effective and safe drug for COVID-19 treatment.
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23
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Kumari M, Kumar A. Can pharmaceutical drugs used to treat Covid-19 infection leads to human health risk? A hypothetical study to identify potential risk. THE SCIENCE OF THE TOTAL ENVIRONMENT 2021; 778:146303. [PMID: 34030377 PMCID: PMC7942154 DOI: 10.1016/j.scitotenv.2021.146303] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Revised: 02/18/2021] [Accepted: 03/02/2021] [Indexed: 05/21/2023]
Abstract
This is the first study to assess human health risks due to the exposure of 'repurposed' pharmaceutical drugs used to treat Covid-19 infection. The study used a six-step approach to determine health risk estimates. For this, consumption of pharmaceuticals under normal circumstances and in Covid-19 infection was compiled to calculate the predicted environmental concentrations (PECs) in river water and in fishes. Risk estimates of pharmaceutical drugs were evaluated for adults as they are most affected by Covid-19 pandemic. Acceptable daily intakes (ADIs) are estimated using the no-observed-adverse-effect-level (NOAEL) or no observable effect level (NOEL) values in rats. The estimated ADI values are then used to calculate predicted no-effect concentrations (PNECs) for three different exposure routes (i) through the accidental ingestion of contaminated surface water during recreational activities only, (ii) through fish consumption only, and (iii) through combined accidental ingestion of contaminated surface water during recreational activities and fish consumption. Higher risk values (hazard quotient, HQ: 337.68, maximum; 11.83, minimum) were obtained for the combined ingestion of contaminated water during recreational activities and fish consumption exposure under the assumptions used in this study indicating possible effects to human health. Amongst the pharmaceutical drugs, ritonavir emerged as main drug, and is expected to pose adverse effects on r human health through fish consumption. Mixture toxicity analysis showed major risk effects of exposure of pharmaceutical drugs (interaction-based hazard index, HIint: from 295.42 (for lopinavir + ritonavir) to 1.20 for chloroquine + rapamycin) demonstrating possible risks due to the co-existence of pharmaceutical in water. The presence of background contaminants in contaminated water does not show any influence on the observed risk estimates as indicated by low HQadd values (<1). Regular monitoring of pharmaceutical drugs in aquatic environment needs to be carried out to reduce the adverse effects of pharmaceutical drugs on human health.
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Affiliation(s)
- Minashree Kumari
- Department of Civil Engineering, Indian Institute of Technology Delhi, Hauz Khas, Delhi 110016, India.
| | - Arun Kumar
- Department of Civil Engineering, Indian Institute of Technology Delhi, Hauz Khas, Delhi 110016, India.
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24
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Maya PG, Mahayasih W, Harizal, Herman, Ahmad I. In silico identification of natural products from Centella asiatica as severe acute respiratory syndromecoronavirus 2 main protease inhibitor. J Adv Pharm Technol Res 2021; 12:261-266. [PMID: 34345605 PMCID: PMC8300333 DOI: 10.4103/japtr.japtr_297_20] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 02/08/2021] [Accepted: 03/28/2021] [Indexed: 11/04/2022] Open
Abstract
Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) main protease (S-CoV-2 Mpro) is one of the main targets in designing antiviral against SARS-CoV-2. Centella asiatica contains several triterpenoids, polyacetylenes, and benzoic ester derivative with various biological activities including anti-inflammation and antiviral. Triterpenoids from C. asiatica could act as inhibitors of S-CoV-2 Mpro. The main objective of this study was to identify potential natural products from C. asiatica as S-CoV-2 Mpro inhibitor with better pharmacokinetic through in silico molecular docking method. : As much as 11 compounds from C. asiatica were docked with S-CoV-2 Mpro (PDB ID: 6LU7) using AutoDock v4.2.6. Pharmacokinetic parameters of these compounds were assessed using SwissADME (free access webserver). Molecular docking results of 11 natural products indicated that asiatate 6 and asiatate 10 have strong interaction with quite similar binding free energy compared to native ligand (‒9.00 and‒9.58 kcal/mol compared to ‒9.18 kcal/mol, respectively) with proper interaction to the catalytic dyad (His41 and Cys145). Pharmacokinetic analysis revealed that asiatate 4, asiatate 10, and asiatate 11 have poor pharmacokinetic properties. These results indicated that asiatate 6 could be recommended for further study as S-CoV-2 Mpro inhibitor.
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Affiliation(s)
- Putu Gita Maya
- Department of Pharmacy, Faculty of Health Sciences, Universitas Esa Unggul, West Jakarta, DKI Jakarta, Indonesia
| | - Widyaswari Mahayasih
- Department of Pharmacy, Faculty of Health Sciences, Universitas Esa Unggul, West Jakarta, DKI Jakarta, Indonesia
| | - Harizal
- Department of Pharmacy, Faculty of Health Sciences, Universitas Esa Unggul, West Jakarta, DKI Jakarta, Indonesia
| | - Herman
- Laboratory of Pharmaceutical Research and Development of FARMAKA TROPIS, Faculty of Pharmacy, Universitas Mulawarman, Samarinda, Indonesia
| | - Islamudin Ahmad
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Mulawarman, Samarinda, East Kalimantan, Indonesia
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25
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McGrowder DA, Miller F, Anderson Cross M, Anderson-Jackson L, Bryan S, Dilworth L. Abnormal Liver Biochemistry Tests and Acute Liver Injury in COVID-19 Patients: Current Evidence and Potential Pathogenesis. Diseases 2021; 9:diseases9030050. [PMID: 34287285 PMCID: PMC8293258 DOI: 10.3390/diseases9030050] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2021] [Revised: 06/16/2021] [Accepted: 06/24/2021] [Indexed: 02/07/2023] Open
Abstract
Globally, millions of persons have contracted the coronavirus disease 2019 (COVID-19) over the past several months, resulting in significant mortality. Health care systems are negatively impacted including the care of individuals with cancers and other chronic diseases such as chronic active hepatitis, cirrhosis and hepatocellular carcinoma. There are various probable pathogenic mechanisms that have been presented to account for liver injury in COVID-19 patients such as hepatotoxicity cause by therapeutic drugs, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of the bile duct cells and hepatocytes, hypoxia and systemic inflammatory response. Liver biochemistry tests such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) are deranged in COVID-19 patients with liver injury. Hepatocellular damage results in the elevation of serum AST and ALT levels in early onset disease while a cholestatic pattern that develops as the disease progress causes higher levels of ALP, GGT, direct and total bilirubin. These liver biochemistry tests are prognostic markers of disease severity and should be carefully monitored in COVID-19 patients. We conducted a systematic review of abnormal liver biochemistry tests in COVID-19 and the possible pathogenesis involved. Significant findings regarding the severity, hepatocellular pattern, incidence and related clinical outcomes in COVID-19 patients are highlighted.
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Affiliation(s)
- Donovan A. McGrowder
- Department of Pathology, Faculty of Medical Sciences, The University of the West Indies, Kingston 7, Jamaica; (L.A.-J.); (L.D.)
- Correspondence:
| | - Fabian Miller
- Department of Physical Education, Faculty of Education, The Mico University College, 1A Marescaux Road, Kingston 5, Jamaica;
- Department of Biotechnology, Faculty of Science and Technology, The University of the West Indies, Kingston 7, Jamaica
| | - Melisa Anderson Cross
- School of Allied Health and Wellness, College of Health Sciences, University of Technology, Kingston 7, Jamaica;
| | - Lennox Anderson-Jackson
- Department of Pathology, Faculty of Medical Sciences, The University of the West Indies, Kingston 7, Jamaica; (L.A.-J.); (L.D.)
| | - Sophia Bryan
- Department of Basic Medical Sciences, Faculty of Medical Sciences, The University of the West Indies, Kingston 7, Jamaica;
| | - Lowell Dilworth
- Department of Pathology, Faculty of Medical Sciences, The University of the West Indies, Kingston 7, Jamaica; (L.A.-J.); (L.D.)
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26
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Adhikary P, Kandel S, Mamani U, Mustafa B, Hao S, Qiu J, Fetse J, Liu Y, Ibrahim NM, Li Y, Lin C, Omoscharka E, Cheng K. Discovery of Small Anti-ACE2 Peptides to Inhibit SARS-CoV-2 Infectivity. ADVANCED THERAPEUTICS 2021; 4:2100087. [PMID: 34179347 PMCID: PMC8212088 DOI: 10.1002/adtp.202100087] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2021] [Indexed: 12/26/2022]
Abstract
COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which infects host cells by binding its viral spike protein receptor-binding domain (RBD) to the angiotensin converting enzyme 2 (ACE2) on host cells. Blocking the SARS-CoV-2-RBD/ACE2 interaction is, therefore, a potential strategy to inhibit viral infections. Using a novel biopanning strategy, a small anti-ACE2 peptide is discovered, which shows high affinity and specificity to human ACE2. It blocks not only the SARS-CoV-2-RBD/ACE2 interaction but also the SARS-CoV-1-RBD/ACE2 interaction. Moreover, it inhibits SARS-CoV-2 infection in Vero-E6 cells. The peptide shows negligible cytotoxicity in Vero-E6 cells and Huh7 cells. In vivo short-term lung toxicity study also demonstrates a good safety of the peptide after intratracheal administration. The anti-ACE2 peptide can be potentially used as a prophylactic or therapeutic agent for SARS-CoV-2 or other ACE2-mediated viruses. The strategy used in this study also provides a fast-track platform to discover other antiviral peptides, which will prepare the world for future pandemics.
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Affiliation(s)
- Pratik Adhikary
- Division of Pharmacology and Pharmaceutical SciencesSchool of PharmacyUniversity of Missouri‐Kansas City2464 Charlotte StreetKansas CityMO64108USA
| | - Sashi Kandel
- Division of Pharmacology and Pharmaceutical SciencesSchool of PharmacyUniversity of Missouri‐Kansas City2464 Charlotte StreetKansas CityMO64108USA
| | - Umar‐Farouk Mamani
- Division of Pharmacology and Pharmaceutical SciencesSchool of PharmacyUniversity of Missouri‐Kansas City2464 Charlotte StreetKansas CityMO64108USA
| | - Bahaa Mustafa
- Division of Pharmacology and Pharmaceutical SciencesSchool of PharmacyUniversity of Missouri‐Kansas City2464 Charlotte StreetKansas CityMO64108USA
| | - Siyuan Hao
- Department of MicrobiologyMolecular Genetics and ImmunologyUniversity of Kansas Medical Center3901 Rainbow BlvdKansas CityKS66160USA
| | - Jianming Qiu
- Department of MicrobiologyMolecular Genetics and ImmunologyUniversity of Kansas Medical Center3901 Rainbow BlvdKansas CityKS66160USA
| | - John Fetse
- Division of Pharmacology and Pharmaceutical SciencesSchool of PharmacyUniversity of Missouri‐Kansas City2464 Charlotte StreetKansas CityMO64108USA
| | - Yanli Liu
- Division of Pharmacology and Pharmaceutical SciencesSchool of PharmacyUniversity of Missouri‐Kansas City2464 Charlotte StreetKansas CityMO64108USA
| | - Nurudeen Mohammed Ibrahim
- Division of Pharmacology and Pharmaceutical SciencesSchool of PharmacyUniversity of Missouri‐Kansas City2464 Charlotte StreetKansas CityMO64108USA
| | - Yongren Li
- Division of Pharmacology and Pharmaceutical SciencesSchool of PharmacyUniversity of Missouri‐Kansas City2464 Charlotte StreetKansas CityMO64108USA
| | - Chien‐Yu Lin
- Division of Pharmacology and Pharmaceutical SciencesSchool of PharmacyUniversity of Missouri‐Kansas City2464 Charlotte StreetKansas CityMO64108USA
| | - Evanthia Omoscharka
- Department of PathologyTruman Medical CenterSchool of MedicineUniversity of Missouri‐Kansas City2301 Holmes StreetKansas CityMO64108USA
| | - Kun Cheng
- Division of Pharmacology and Pharmaceutical SciencesSchool of PharmacyUniversity of Missouri‐Kansas City2464 Charlotte StreetKansas CityMO64108USA
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27
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Istampoulouoglou I, Zimmermanns B, Grandinetti T, Marzolini C, Harings-Kaim A, Koechlin-Lemke S, Scholz I, Bassetti S, Leuppi-Taegtmeyer AB. Cardiovascular adverse effects of lopinavir/ritonavir and hydroxychloroquine in COVID-19 patients: Cases from a single pharmacovigilance centre. Glob Cardiol Sci Pract 2021; 2021:e202111. [PMID: 34285902 PMCID: PMC8272412 DOI: 10.21542/gcsp.2021.11] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2021] [Accepted: 05/31/2021] [Indexed: 01/08/2023] Open
Abstract
In this article we summarize the cardiovascular adverse events that were observed in three patients during their treatment for COVID-19 and discuss their association with lopinavir/ ritonavir (LPV/r) and hydroxychloroquine (HCQ). The cases were reported to our regional pharmacovigilance centre in April 2020. All three patients were above 75 years in age, male and multimorbid, and had been hospitalized for treatment of COVID-19. As part of their treatment, all of them received a very strictly monitored off-label therapy with LPV/r and HCQ, for which they had given their prior, written, informed consent. In one patient, erythromycin was also administered. All three patients developed a significant QTc time prolongation during or shortly after therapy with the above drugs. On account of this, the treatment had to be discontinued early in each case and QTc time recovered in all three patients.
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Affiliation(s)
- Ioanna Istampoulouoglou
- Department of Clinical Pharmacology & Toxicology, University Hospital Basel, Switzerland.,University of Basel, Basel, Switzerland
| | - Barbara Zimmermanns
- Department of Clinical Pharmacology & Toxicology, University Hospital Basel, Switzerland.,Regional Pharmacovigilance Centre Basel, University Hospital Basel, Switzerland.,University of Basel, Basel, Switzerland
| | - Tanja Grandinetti
- Department of Clinical Pharmacology & Toxicology, University Hospital Basel, Switzerland.,University of Basel, Basel, Switzerland
| | - Catia Marzolini
- Division of Infectious Diseases & Hospital Hygiene, University Hospital Basel, Switzerland.,University of Basel, Basel, Switzerland
| | - Annette Harings-Kaim
- Regional Pharmacovigilance Centre Basel, University Hospital Basel, Switzerland.,University of Basel, Basel, Switzerland
| | - Sarah Koechlin-Lemke
- Department of Clinical Pharmacology & Toxicology, University Hospital Basel, Switzerland.,Regional Pharmacovigilance Centre Basel, University Hospital Basel, Switzerland.,University of Basel, Basel, Switzerland
| | - Irene Scholz
- Swissmedic, Schweizerisches Heilmittelinstitut, Bern, Switzerland
| | - Stefano Bassetti
- Division of Internal Medicine, University Hospital Basel, Switzerland.,University of Basel, Basel, Switzerland
| | - Anne B Leuppi-Taegtmeyer
- Department of Clinical Pharmacology & Toxicology, University Hospital Basel, Switzerland.,Regional Pharmacovigilance Centre Basel, University Hospital Basel, Switzerland.,University of Basel, Basel, Switzerland
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28
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Negrut N, Codrean A, Hodisan I, Bungau S, Tit DM, Marin R, Behl T, Banica F, Diaconu CC, Nistor-Cseppento DC. Efficiency of antiviral treatment in COVID-19. Exp Ther Med 2021; 21:648. [PMID: 33968179 PMCID: PMC8097236 DOI: 10.3892/etm.2021.10080] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Accepted: 03/31/2021] [Indexed: 12/12/2022] Open
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is responsible for generating a global effort to discover urgent therapeutic solutions to limit the human damage caused by COVID-19. In the period of April to June 2020, 105 patients diagnosed with COVID-19 met the conditions for inclusion in the present study. They were treated with antiviral therapy according to local guidelines: D group (53 cases), treated with darunavir/ritonavir (DRV/r); and K group (52 cases), treated with lopinavir/ritonavir (LPV/r). Patients from the K group required 7.5 days of hospitalization less compared to those from the D group (P<0.001). The blood oxygen saturation values recorded in the groups were statistically different [K group (94.02±3.12%) vs. D group (92.13±4.24%), P=0.010]. The percentage of patients with unsatisfactory clinical evolution were non-significantly higher in the D group compared with the K group [20 (37.74%) vs. 12 (23.08%), P=0.157]. We did not note statistically significant differences between the two groups tracked considering the values for the Brescia-COVID Respiratory Severity Scale (BCRSS) of the patients with unsatisfactory clinical evolution, nor of the chest CT' evolution after 10 days of therapy. We did not register significant adverse effects after antiviral therapy in the two groups. Antiviral therapy with LPV/r had some favorable results compared to DRV/r in patients with COVID-19. Both therapies were well tolerated.
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Affiliation(s)
- Nicoleta Negrut
- Department of Psycho-Neuroscience and Recovery, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
| | - Adriana Codrean
- Department of Psycho-Neuroscience and Recovery, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
| | - Ioana Hodisan
- Department of infectious Diseases, ‘Gavril Curteanu’ Municipal Hospital Oradea, 410469 Oradea, Romania
| | - Simona Bungau
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania
| | - Delia Mirela Tit
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania
| | - Ruxandra Marin
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania
| | - Tapan Behl
- Chitkara College of Pharmacy, Chitkara University, 140401 Punjab, India
| | - Florin Banica
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania
| | - Camelia C. Diaconu
- Department 5, ‘Carol Davila’ University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Delia Carmen Nistor-Cseppento
- Department of Psycho-Neuroscience and Recovery, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
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29
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Nguyen KV. Problems associated with antiviral drugs and vaccines development for COVID-19: approach to intervention using expression vectors via GPI anchor. NUCLEOSIDES, NUCLEOTIDES & NUCLEIC ACIDS 2021; 40:665-706. [PMID: 33982646 PMCID: PMC8127170 DOI: 10.1080/15257770.2021.1914851] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/28/2020] [Revised: 04/06/2021] [Accepted: 04/06/2021] [Indexed: 12/03/2022]
Abstract
The outbreak of a novel coronavirus responsible for the severe acquired respiratory syndrome: SARS-CoV-2, also known as coronavirus disease 2019: COVID-19, represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for diagnostic, development of antibodies, entry inhibitors, and vaccines. COVID-19 also recognizes angiotensin-converting enzyme 2 (ACE2) as its host receptor binding to viral S protein. Several antiviral drugs and vaccines have been evaluated for the treatment and prevention of the infection by the virus. To facilitate medical countermeasure development, the problems associated with antiviral drugs and vaccines development for containing the spread of COVID-19 are discussed. There is an urgent need to study deeply on the structure, mutations, and function of COVID-19 as well as its pathophysiology from a large population. Construction of expression vectors for any protein targeting to the cell plasma membrane via the glycosyl-phosphatidylinositol, GPI, anchor for studying intermolecular interactions, as described in Ref. # 62 (Nguyen, K. V., Naviaux, R. K., Nyhan, W. L. Lesch-Nyhan disease: I. Construction of expression vectors for hypoxanthine-guanine phosphoribosyltransferase (HGprt) enzyme and amyloid precursor protein (APP). Nucleosides Nucleotides Nucleic Acids 2020, 39, 905-922), between the S protein of COVID-19 as well as its variants and ACE2 could be useful in antiviral drugs and vaccines development.
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Affiliation(s)
- Khue Vu Nguyen
- Department of Medicine, Biochemical Genetics and Metabolism, The Mitochondrial and Metabolic Disease Center, School of Medicine, University of California, San Diego, San Diego, CA, USA
- Department of Pediatrics, University of California, San Diego, School of Medicine, CA, USA
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30
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Abeldaño Zuñiga RA, Coca SM, Abeldaño GF, González-Villoria RAM. Clinical effectiveness of drugs in hospitalized patients with COVID-19: a systematic review and meta-analysis. Ther Adv Respir Dis 2021; 15:17534666211007214. [PMID: 33765902 PMCID: PMC8010807 DOI: 10.1177/17534666211007214] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
The aim was to assess the clinical effectiveness of drugs used in hospitalized patients with COVID-19 infection. We conducted a systematic review of randomized clinical trials assessing treatment with remdesivir, chloroquine, hydroxychloroquine, lopinavir, ritonavir, dexamethasone, and convalescent plasma, for hospitalized patients with a diagnosis of SARS-CoV-2 infection. The outcomes were mortality, clinical improvement, duration of ventilation, duration of oxygen support, duration of hospitalization, virological clearance, and severe adverse events. A total of 48 studies were retrieved from the databases. Eleven articles were finally included in the data extraction and qualitative synthesis of results. The meta-analysis suggests a benefit of dexamethasone versus standard care in the reduction of risk of mortality at day 28; and the clinical improvement at days 14 and 28 in patients treated with remdesivir. We can conclude that dexamethasone would have a better result in hospitalized patients, especially in low-resources settings. The analysis of the main treatments proposed for hospitalized patients is of vital importance to reduce mortality in low-income countries, since the COVID-19 pandemic had an economic impact worldwide with the loss of jobs and economic decline in countries with scarce resources. The reviews of this paper are available via the supplemental material section.
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Affiliation(s)
- Roberto Ariel Abeldaño Zuñiga
- Guillermo Rojas Mijangos SN, Ciudad Universitaria, Miahuatlan de Porfirio Diaz, Oaxaca, 70800, Mexico.,Postgraduate Department, University of Sierra Sur, Miahuatlan de Porfirio Diaz, Oaxaca, 70800, Mexico
| | - Silvia Mercedes Coca
- Public Health Research Institute, University of Sierra Sur, Miahuatlan de Porfirio Diaz, Oaxaca, Mexico
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31
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Lopes-Pacheco M, Silva PL, Cruz FF, Battaglini D, Robba C, Pelosi P, Morales MM, Caruso Neves C, Rocco PRM. Pathogenesis of Multiple Organ Injury in COVID-19 and Potential Therapeutic Strategies. Front Physiol 2021; 12:593223. [PMID: 33584343 PMCID: PMC7876335 DOI: 10.3389/fphys.2021.593223] [Citation(s) in RCA: 109] [Impact Index Per Article: 27.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Accepted: 01/08/2021] [Indexed: 01/08/2023] Open
Abstract
Severe acute respiratory disease coronavirus 2 (SARS-CoV-2, formerly 2019-nCoV) is a novel coronavirus that has rapidly disseminated worldwide, causing the coronavirus disease 2019 (COVID-19) pandemic. As of January 6th, 2021, there were over 86 million global confirmed cases, and the disease has claimed over 1.87 million lives (a ∼2.2% case fatality rate). SARS-CoV-2 is able to infect human cells by binding its spike (S) protein to angiotensin-conversing enzyme 2 (ACE2), which is expressed abundantly in several cell types and tissues. ACE2 has extensive biological activities as a component of the renin-angiotensin-aldosterone system (RAAS) and plays a pivotal role as counter-regulator of angiotensin II (Ang II) activity by converting the latter to Ang (1-7). Virion binding to ACE2 for host cell entry leads to internalization of both via endocytosis, as well as activation of ADAM17/TACE, resulting in downregulation of ACE2 and loss of its protective actions in the lungs and other organs. Although COVID-19 was initially described as a purely respiratory disease, it is now known that infected individuals can rapidly progress to a multiple organ dysfunction syndrome. In fact, all human structures that express ACE2 are susceptible to SARS-CoV-2 infection and/or to the downstream effects of reduced ACE2 levels, namely systemic inflammation and injury. In this review, we aim to summarize the major features of SARS-CoV-2 biology and the current understanding of COVID-19 pathogenesis, as well as its clinical repercussions in the lung, heart, kidney, bowel, liver, and brain. We also highlight potential therapeutic targets and current global efforts to identify safe and effective therapies against this life-threatening condition.
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Affiliation(s)
- Miquéias Lopes-Pacheco
- Biosystems & Integrative Sciences Institute, Faculty of Sciences, University of Lisbon, Lisbon, Portugal
| | - Pedro Leme Silva
- Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
- National Institute of Science and Technology for Regenerative Medicine, Rio de Janeiro, Brazil
- Rio de Janeiro Innovation Network in Nanosystems for Health-NanoSAÚDE/FAPERJ, Rio de Janeiro, Brazil
- COVID-19 Virus Network, Ministry of Science, Technology and Innovation, Brasília, Brazil
- COVID-19 Virus Network, Brazilian Council for Scientific and Technological Development, Brasília, Brazil
- COVID-19 Virus Network, Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro – FAPERJ, Rio de Janeiro, Brazil
| | - Fernanda Ferreira Cruz
- Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
- National Institute of Science and Technology for Regenerative Medicine, Rio de Janeiro, Brazil
- Rio de Janeiro Innovation Network in Nanosystems for Health-NanoSAÚDE/FAPERJ, Rio de Janeiro, Brazil
- COVID-19 Virus Network, Ministry of Science, Technology and Innovation, Brasília, Brazil
- COVID-19 Virus Network, Brazilian Council for Scientific and Technological Development, Brasília, Brazil
- COVID-19 Virus Network, Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro – FAPERJ, Rio de Janeiro, Brazil
| | - Denise Battaglini
- Anesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neuroscience, Genoa, Italy
| | - Chiara Robba
- Anesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neuroscience, Genoa, Italy
| | - Paolo Pelosi
- Anesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neuroscience, Genoa, Italy
- Department of Surgical Sciences and Integrated Diagnostic, University of Genoa, Genoa, Italy
| | - Marcelo Marcos Morales
- National Institute of Science and Technology for Regenerative Medicine, Rio de Janeiro, Brazil
- Rio de Janeiro Innovation Network in Nanosystems for Health-NanoSAÚDE/FAPERJ, Rio de Janeiro, Brazil
- COVID-19 Virus Network, Ministry of Science, Technology and Innovation, Brasília, Brazil
- COVID-19 Virus Network, Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro – FAPERJ, Rio de Janeiro, Brazil
- Laboratory of Cellular and Molecular Physiology, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Celso Caruso Neves
- National Institute of Science and Technology for Regenerative Medicine, Rio de Janeiro, Brazil
- Rio de Janeiro Innovation Network in Nanosystems for Health-NanoSAÚDE/FAPERJ, Rio de Janeiro, Brazil
- COVID-19 Virus Network, Brazilian Council for Scientific and Technological Development, Brasília, Brazil
- COVID-19 Virus Network, Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro – FAPERJ, Rio de Janeiro, Brazil
- Laboratory of Biochemistry and Cell Signaling, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Patricia Rieken Macedo Rocco
- Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
- National Institute of Science and Technology for Regenerative Medicine, Rio de Janeiro, Brazil
- Rio de Janeiro Innovation Network in Nanosystems for Health-NanoSAÚDE/FAPERJ, Rio de Janeiro, Brazil
- COVID-19 Virus Network, Ministry of Science, Technology and Innovation, Brasília, Brazil
- COVID-19 Virus Network, Brazilian Council for Scientific and Technological Development, Brasília, Brazil
- COVID-19 Virus Network, Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro – FAPERJ, Rio de Janeiro, Brazil
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Lee C, Choi WJ. Overview of COVID-19 inflammatory pathogenesis from the therapeutic perspective. Arch Pharm Res 2021; 44:99-116. [PMID: 33398692 PMCID: PMC7781412 DOI: 10.1007/s12272-020-01301-7] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Accepted: 12/01/2020] [Indexed: 02/08/2023]
Abstract
The novel beta coronavirus (SARS-CoV-2, designated as COVID-19) that is responsible for severe acute respiratory syndrome has devastated the global economy and health care system. Since COVID-19 changed the definition of “normal” in ordinary life around the world, the development of effective therapeutics and preventive measures is desperately needed to fight SARS-CoV-2 infection and restore normalcy. A clear understanding of COVID-19 pathogenesis is crucial in providing the scientific rationale necessary to develop anti-COVID19 drugs and vaccines. According to the most recently published literature, COVID-19 pathogenesis was postulated to occur in three sequential phases: pulmonary, proinflammatory, and prothrombic. Herein, virus-host interactions, potential pathogenic mechanisms, and clinical manifestations are described for each phase. Additionally, based on this pathogenesis model, various therapeutic strategies involving current clinical trials are presented with an explanation of their modes of action and example drugs. This review is a thorough, updated summary of COVID-19 pathogenesis and the therapeutic options available for this disease.
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Affiliation(s)
- Choongho Lee
- College of Pharmacy, Dongguk University, Goyang, 10326, Republic of Korea.
| | - Won Jun Choi
- College of Pharmacy, Dongguk University, Goyang, 10326, Republic of Korea
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Hossain MJ, Rahman SMA. Repurposing therapeutic agents against SARS-CoV-2 infection: most promising and neoteric progress. Expert Rev Anti Infect Ther 2020; 19:1009-1027. [PMID: 33355520 DOI: 10.1080/14787210.2021.1864327] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
INTRODUCTION The pathogenic and highly transmissible etiological agent, SARS-CoV-2, has caused a serious threat COVID-19 pandemic. WHO has declared the epidemic a public health emergency of international concern owing to its high contagiosity, mortality rate, and morbidity. Till now, there is no approved vaccine or drug to combat the COVID-19 and avert this global crisis. AREAS COVERED In this narrative review, we summarized the updated results (January to August 2020) of the most promising repurposing therapeutic candidates to treat the SARS-CoV-2 viral infection. The repurposed drugs classified under four headlines like antivirals, anti-parasitic, immune-modulating, and miscellaneous drugs were discussed with their in vitro efficacy to recent clinical advancements against COVID-19. EXPERT OPINION Currently, palliative care, ranging from outpatient management to intensive care, including oxygen administration, ventilator support, intravenous fluids therapy, with some repurposed drugs, are the primary weapons to fight against COVID-19. Until a safe and effective vaccine is developed, an evidence-based drug repurposing strategy might be the wisest option to save people from this catastrophe. Several existing drugs are now under clinical trials, and some of them are approved in different places of the world for emergency use or as adjuvant therapy in COVID-19 with standard of care.
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Affiliation(s)
- Md Jamal Hossain
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Dhaka, Dhaka-1000, Bangladesh
| | - S M Abdur Rahman
- Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka-1000, Bangladesh
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Drożdżal S, Rosik J, Lechowicz K, Machaj F, Kotfis K, Ghavami S, Łos MJ. FDA approved drugs with pharmacotherapeutic potential for SARS-CoV-2 (COVID-19) therapy. Drug Resist Updat 2020; 53:100719. [PMID: 32717568 PMCID: PMC7362818 DOI: 10.1016/j.drup.2020.100719] [Citation(s) in RCA: 91] [Impact Index Per Article: 18.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2020] [Revised: 07/10/2020] [Accepted: 07/13/2020] [Indexed: 02/06/2023]
Abstract
In December 2019, a novel SARS-CoV-2 coronavirus emerged, causing an outbreak of life-threatening pneumonia in the Hubei province, China, and has now spread worldwide, causing a pandemic. The urgent need to control the disease, combined with the lack of specific and effective treatment modalities, call for the use of FDA-approved agents that have shown efficacy against similar pathogens. Chloroquine, remdesivir, lopinavir/ritonavir or ribavirin have all been successful in inhibiting SARS-CoV-2 in vitro. The initial results of a number of clinical trials involving various protocols of administration of chloroquine or hydroxychloroquine mostly point towards their beneficial effect. However, they may not be effective in cases with persistently high viremia, while results on ivermectin (another antiparasitic agent) are not yet available. Interestingly, azithromycin, a macrolide antibiotic in combination with hydroxychloroquine, might yield clinical benefit as an adjunctive. The results of clinical trials point to the potential clinical efficacy of antivirals, especially remdesivir (GS-5734), lopinavir/ritonavir, and favipiravir. Other therapeutic options that are being explored involve meplazumab, tocilizumab, and interferon type 1. We discuss a number of other drugs that are currently in clinical trials, whose results are not yet available, and in various instances we enrich such efficacy analysis by invoking historic data on the treatment of SARS, MERS, influenza, or in vitro studies. Meanwhile, scientists worldwide are seeking to discover novel drugs that take advantage of the molecular structure of the virus, its intracellular life cycle that probably elucidates unfolded-protein response, as well as its mechanism of surface binding and cell invasion, like angiotensin converting enzymes-, HR1, and metalloproteinase inhibitors.
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Affiliation(s)
- Sylwester Drożdżal
- Department of Pharmacokinetics and Monitored Therapy, Pomeranian Medical University in Szczecin, Poland
| | - Jakub Rosik
- Department of Pathology, Pomeranian Medical University in Szczecin, Poland
| | - Kacper Lechowicz
- Department of Anaesthesiology, Intensive Therapy and Acute Intoxications, Pomeranian Medical University in Szczecin, Poland
| | - Filip Machaj
- Department of Pathology, Pomeranian Medical University in Szczecin, Poland
| | - Katarzyna Kotfis
- Department of Anaesthesiology, Intensive Therapy and Acute Intoxications, Pomeranian Medical University in Szczecin, Poland
| | - Saeid Ghavami
- Department of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada
| | - Marek J Łos
- Biotechnology Centre, Silesian University of Technology, Krzywoustego 8 Str., 44-100, Gliwice, Poland.
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35
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Babaei F, Mirzababaei M, Nassiri-Asl M, Hosseinzadeh H. Review of registered clinical trials for the treatment of COVID-19. Drug Dev Res 2020; 82:474-493. [PMID: 33251593 PMCID: PMC7753306 DOI: 10.1002/ddr.21762] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Revised: 11/05/2020] [Accepted: 11/13/2020] [Indexed: 01/08/2023]
Abstract
Coronavirus disease 2019 (COVID‐19) is a viral disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). The disease was first reported in December 2019 in Wuhan, China, but now more than 200 countries have been affected and the coronavirus pandemic is still ongoing. The severity of COVID‐19 symptoms can range from mild to severe. FDA approved remdesivir as a treatment of COVID‐19 so far. Various clinical trials are underway to find an effective method to treat patients with COVID‐19. This review aimed at summarizing 219 registered clinical trials in the ClinicalTrials.gov database with possible mechanisms, and novel findings of them, and other recent publications related to COVID‐19. According to our analyses, various treatment approaches and drugs are being investigated to find an effective drug to cure COVID‐19 and among all strategies, three important mechanisms are suggested to be important against COVID‐19 including antiviral, anti‐inflammatory, and immunomodulatory properties. Our review can help future studies get on the way to finding an effective drug for COVID‐19 treatment by providing ideas for similar researches.
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Affiliation(s)
- Fatemeh Babaei
- Department of Clinical Biochemistry, School of Medicine, Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammadreza Mirzababaei
- Department of Clinical Biochemistry, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Marjan Nassiri-Asl
- Department of Pharmacology and Neurobiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hossein Hosseinzadeh
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.,Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
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36
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Horby PW, Mafham M, Bell JL, Linsell L, Staplin N, Emberson J, Palfreeman A, Raw J, Elmahi E, Prudon B, Green C, Carley S, Chadwick D, Davies M, Wise MP, Baillie JK, Chappell LC, Faust SN, Jaki T, Jefferey K, Lim WS, Montgomery A, Rowan K, Juszczak E, Haynes R, Landray MJ. Lopinavir-ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet 2020; 396:1345-1352. [PMID: 33031764 PMCID: PMC7535623 DOI: 10.1016/s0140-6736(20)32013-4] [Citation(s) in RCA: 462] [Impact Index Per Article: 92.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Revised: 09/07/2020] [Accepted: 09/17/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Lopinavir-ritonavir has been proposed as a treatment for COVID-19 on the basis of in vitro activity, preclinical studies, and observational studies. Here, we report the results of a randomised trial to assess whether lopinavir-ritonavir improves outcomes in patients admitted to hospital with COVID-19. METHODS In this randomised, controlled, open-label, platform trial, a range of possible treatments was compared with usual care in patients admitted to hospital with COVID-19. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients were randomly allocated to either usual standard of care alone or usual standard of care plus lopinavir-ritonavir (400 mg and 100 mg, respectively) by mouth for 10 days or until discharge (or one of the other RECOVERY treatment groups: hydroxychloroquine, dexamethasone, or azithromycin) using web-based simple (unstratified) randomisation with allocation concealment. Randomisation to usual care was twice that of any of the active treatment groups (eg, 2:1 in favour of usual care if the patient was eligible for only one active group, 2:1:1 if the patient was eligible for two active groups). The primary outcome was 28-day all-cause mortality. Analyses were done on an intention-to-treat basis in all randomly assigned participants. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. FINDINGS Between March 19, 2020, and June 29, 2020, 1616 patients were randomly allocated to receive lopinavir-ritonavir and 3424 patients to receive usual care. Overall, 374 (23%) patients allocated to lopinavir-ritonavir and 767 (22%) patients allocated to usual care died within 28 days (rate ratio 1·03, 95% CI 0·91-1·17; p=0·60). Results were consistent across all prespecified subgroups of patients. We observed no significant difference in time until discharge alive from hospital (median 11 days [IQR 5 to >28] in both groups) or the proportion of patients discharged from hospital alive within 28 days (rate ratio 0·98, 95% CI 0·91-1·05; p=0·53). Among patients not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion who met the composite endpoint of invasive mechanical ventilation or death (risk ratio 1·09, 95% CI 0·99-1·20; p=0·092). INTERPRETATION In patients admitted to hospital with COVID-19, lopinavir-ritonavir was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death. These findings do not support the use of lopinavir-ritonavir for treatment of patients admitted to hospital with COVID-19. FUNDING Medical Research Council and National Institute for Health Research.
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37
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Abdelzaher H, Saleh BM, Ismail HA, Hafiz M, Gabal MA, Mahmoud M, Hashish S, Gawad RMA, Gharieb RY, Abdelnaser A. COVID-19 Genetic and Environmental Risk Factors: A Look at the Evidence. Front Pharmacol 2020; 11:579415. [PMID: 33117174 PMCID: PMC7577231 DOI: 10.3389/fphar.2020.579415] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Accepted: 09/07/2020] [Indexed: 01/08/2023] Open
Abstract
The Covid-19 pandemic is with no doubt the biggest health crisis of the 21st century. The disease is caused by a virus of the Coronaviridae family and is closely related to the virus responsible for the severe acute respiratory Syndrome (SARS). Since December 2019, the virus has continued to spread way beyond the location of the first recorded cases (Wuhan, China). As of now, over 5 million cases have been diagnosed with the disease worldwide and over 300 thousand have died. COVID-19 patients suffer from respiratory symptoms that can rapidly turn into potentially fatal acute respiratory distress syndrome (ARDS) in a portion of patients. Although many drugs and vaccines are currently under clinical trials, there is no currently approved treatment or vaccine. It is therefore critical to correctly identify risk factors that lead to the exacerbation of symptoms in highly susceptible groups. Groups that are at high risk include those aged 55 or older especially those with underlying conditions such as cardiovascular diseases. Certain ethnicities such as African-Americans have been found to be at a higher risk and males seem to be higher both in numbers as well as severity of cases. It is hypothesized that these groups are at risk as their molecular landscape is more permissive of viral infection and growth. Different occupations, especially those related to health-care as well as populations that do not cultivate a mask-wearing culture are at higher risk due to environmental exposure. In this article, we examine the evidence regarding different groups that are more sensitive to the disease and review hypotheses pertaining to COVID-19 infection and prognosis. Risk factors that can be related to the molecular landscape of COVID-19 infection as well as those related to environmental and occupational conditions are discussed.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Anwar Abdelnaser
- School of Science and Engineering, Institute of Global Health and Human Ecology, The American University in Cairo, Cairo, Egypt
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Kumar R, Srivastava JK, Singh R, Siddiqui MH, Mansouri RA, Abdulhakim JA, Bin-Jumah MN, Alkahtani S, Abdel-Daim MM, Uddin MS. Available Compounds With Therapeutic Potential Against COVID-19: Antimicrobial Therapies, Supportive Care, and Probable Vaccines. Front Pharmacol 2020; 11:582025. [PMID: 33123014 PMCID: PMC7573470 DOI: 10.3389/fphar.2020.582025] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Accepted: 09/15/2020] [Indexed: 12/15/2022] Open
Abstract
The recent outbreak of the COVID-2019 (coronavirus disease 2019) due to the infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has realized the requirement of alternative therapeutics to mitigate and alleviate this lethal infection. These alternative therapies are effective when they are started at the initial stage of the infection. Some drugs that were used in previous other related infections SARS-CoV-2003 and Middle East respiratory syndrome coronavirus (MERS-CoV)-2012 could be potentially active against currently emerging SARS-CoV-2. This fact imparts some rationale of current interventions, in the absence of any specific therapeutics for SARS-CoV-2. It is imperative to focus on the available antimicrobial and adjunct therapies during the current emergency state and overcome the challenges associated with the absence of robust controlled studies. There is no established set of drugs to manage SARS-CoV-2 infected patients. However, closely following patients’ conditions and responding with the dosage guidelines of available drugs may significantly impact our ability to slow down the infection. Of note, it depends upon the condition of the patients and associated comorbid; therefore, the health workers need to choose the drug combinations judiciously until COVID-19 specific drug or vaccine is developed with the collective scientific rigor. In this article, we reviewed the available antimicrobial drug, supportive therapies, and probable high importance vaccines for the COVID-19 treatment.
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Affiliation(s)
- Rajnish Kumar
- Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow Campus, Lucknow, India
| | | | - Rachana Singh
- Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow Campus, Lucknow, India
| | | | - Rasha A Mansouri
- Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Jawaher A Abdulhakim
- Department of Medical Laboratory, Faculty of Applied Medical Sciences, Taibah University, Yanbu, Saudi Arabia
| | - May N Bin-Jumah
- Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Saad Alkahtani
- Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Mohamed M Abdel-Daim
- Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia.,Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, Egypt
| | - Md Sahab Uddin
- Department of Pharmacy, Southeast University, Dhaka, Bangladesh.,Pharmakon Neuroscience Research Network, Dhaka, Bangladesh
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Lundstrom K. Coronavirus pandemic: treatment and future prevention. Future Microbiol 2020; 15:1507-1521. [PMID: 33140657 PMCID: PMC7675013 DOI: 10.2217/fmb-2020-0174] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Accepted: 10/05/2020] [Indexed: 02/06/2023] Open
Abstract
The rapid spread of SARS-CoV-2 leading to the COVID-19 pandemic with more than 400,000 deaths worldwide and the global economy shut down has substantially accelerated the research and development of novel and efficient COVID-19 antiviral drugs and vaccines. In the short term, antiviral and other drugs have been subjected to repurposing against COVID-19 demonstrating some success, but some excessively hasty conclusions drawn from significantly suboptimal clinical evaluations have provided false hope. On the other hand, more than 300 potential therapies and at least 150 vaccine studies are in progress at various stages of preclinical or clinical research. The aim here is to provide a timely update of the development, which, due to the intense activities, moves forward with unprecedented speed.
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40
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Esposito S, Gnocchi M, Gagliardi M, Affanni P, Veronesi L, Colucci ME, Neglia C, Argentiero A, Principi N. Therapeutic strategies against COVID-19. ACTA BIO-MEDICA : ATENEI PARMENSIS 2020; 91:e2020038. [PMID: 32921732 PMCID: PMC7716986 DOI: 10.23750/abm.v91i3.10450] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Subscribe] [Scholar Register] [Received: 08/15/2020] [Accepted: 08/17/2020] [Indexed: 12/15/2022]
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that mainly affects the upper and lower respiratory tract and is responsible for extremely different degrees of disease, ranging from flu-like symptoms to atypical pneumonia that may evolve to acute respiratory distress syndrome and, ultimately, death. No specific therapy for SARS-CoV-2 has yet been identified, but since the beginning of the outbreak, several pre-existing therapeutics have been reconsidered for the treatment of infected patients. The aim of this article is to discuss current therapeutics against SARS-CoV-2. A literature review was performed using PubMed, collecting data from English-language articles published until June 20th, 2020. Literature analysis showed that with the acquisition of more in-depth knowledge on the characteristics of SARS-CoV-2 and the pathogenesis of the different clinical manifestations, a more rationale use of available drugs has become possible. However, the road to defining which drugs are effective and which schedules of administration must be used to maximize efficacy and minimize adverse events is still very long. To date, it is only clear that no drug can alone cope with all the problems posed by SARS-CoV-2 infection and effective antivirals and inflammatory drugs must be given together to reduce COVID-19 clinical manifestations. Moreover, choice of therapy must always be tailored on clinical manifestations and, when they occur, drugs able to fight coagulopathy and venous thromboembolism that may contribute to respiratory deterioration must be prescribed.
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Affiliation(s)
| | - Margherita Gnocchi
- Pediatric Clinic, Pietro Barilla Children's Hospital, Department of Medicine and Surgery, University of Parma, Parma, Italy.
| | - Martina Gagliardi
- Pediatric Clinic, Pietro Barilla Children's Hospital, Department of Medicine and Surgery, University of Parma, Parma, Italy.
| | - Paola Affanni
- Department of Medicine and Surgery, University of Parma, Italy.
| | - Licia Veronesi
- Department of Medicine and Surgery, University of Parma, Italy.
| | | | - Cosimo Neglia
- Pediatric Clinic, Pietro Barilla Children's Hospital, Department of Medicine and Surgery, University of Parma, Parma, Italy.
| | - Alberto Argentiero
- Pediatric Clinic, Pietro Barilla Children's Hospital, Department of Medicine and Surgery, University of Parma, Parma, Italy.
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Costenaro P, Minotti C, Barbieri E, Giaquinto C, Donà D. SARS-CoV-2 infection in people living with HIV: a systematic review. Rev Med Virol 2020; 31:1-12. [PMID: 32875716 DOI: 10.1002/rmv.2155] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Revised: 07/24/2020] [Accepted: 07/27/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND SETTING Little is known about SARS-CoV-2 impact on some vulnerable subgroups, such as people living with HIV/AIDS (PLWHA). In our study we reviewed the current knowledge on SARS-CoV-2 cases in PLWHA. METHODS A systematic review was conducted by searching the MEDLINE, EMBASE and Google Scholar databases. Studies reporting data on PLWHA affected by SARS-CoV-2 were considered for inclusion. The aim of this study was the systematic characterization of cases of SARS-CoV-2 infection among PLWHA, particularly focusing on age, clinical findings at diagnosis, radiological features, therapeutic management and clinical outcomes. RESULTS Twenty three relevant articles were identified, which reported 164 adults with both HIV and SARS-CoV-2 infection. Of those, the large majority were males (120/142, 84.5%), often with one or more comorbidities. Fifteen cases needed intensive care treatment and 16 died. For each group, respectively three patients had underlying comorbidities. There were no studies on children. The included studies were mostly retrospective or case series/reports (19 studies). The overall risk of bias was moderate, due to the study types and characteristics. CONCLUSION It is still unclear if HIV infection may influence SARS-CoV-2 infection and disease course, however some PLWHA and particularly males affected by ARV-related complications may be at greater risk of severe Covid-19 course.
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Affiliation(s)
- Paola Costenaro
- Division of Pediatric Infectious Diseases, Department of Women's and Children's Health, University of Padua, Padua, Italy.,Infectious Diseases Department, Alto Vicentino Hospital, Santorso (Vicenza), Italy
| | - Chiara Minotti
- Department of Women's and Children's Health, University of Padua, Padua, Italy
| | - Elisa Barbieri
- Division of Pediatric Infectious Diseases, Department of Women's and Children's Health, University of Padua, Padua, Italy
| | - Carlo Giaquinto
- Division of Pediatric Infectious Diseases, Department of Women's and Children's Health, University of Padua, Padua, Italy
| | - Daniele Donà
- Division of Pediatric Infectious Diseases, Department of Women's and Children's Health, University of Padua, Padua, Italy
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Benani A, Ben Mkaddem S. Mechanisms Underlying Potential Therapeutic Approaches for COVID-19. Front Immunol 2020; 11:1841. [PMID: 32793246 PMCID: PMC7385230 DOI: 10.3389/fimmu.2020.01841] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Accepted: 07/08/2020] [Indexed: 12/16/2022] Open
Abstract
Coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is a betacoronavirus, and is associated with cytokine storm inflammation and lung injury, leading to respiratory distress. The transmission of the virus is mediated by human contact. To control and prevent the spread of this virus, the majority of people worldwide are facing quarantine; patients are being subjected to non-specific treatments under isolation. To prevent and stop the COVID-19 pandemic, several clinical trials are in the pipeline. The current clinical trials either target the intracellular replication and spread of the virus or the cytokine storm inflammation seen in COVID-19 cases during the later stages of the disease. Since both targeting strategies are different, the window drug administration plays a crucial role in the efficacy of the treatment. Here, we review the mechanism underlying SARS-CoV-2 cell infection and potential future therapeutic approaches.
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Affiliation(s)
- Abdelouaheb Benani
- Unité de Biologie Moléculaire, Institut Pasteur du Maroc, Casablanca, Morocco
| | - Sanae Ben Mkaddem
- U978 Institut National de la Santé et de la Recherche Médicale, Bobigny, France.,UFR SMBH, Université Sorbonne Paris Nord, Bobigny, France
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