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Review of four major biomolecular target sites for COVID-19 and possible inhibitors as treatment interventions

Vigbedor et al., Journal of Applied Pharmaceutical Science, doi:10.7324/JAPS.2021.110825
May 2021  
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HCQ for COVID-19
1st treatment shown to reduce risk in March 2020
 
*, now known with p < 0.00000000001 from 422 studies, recognized in 42 countries.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
3,900+ studies for 60+ treatments. c19hcq.org
Review of major target sites in SARS-CoV-2 and the host organism along with potential inhibitors.
Reviews covering hydroxychloroquine for COVID-19 include Al-Bari, Brouqui, Colson, Derwand, Gao, Goldstein, Hecel, IHU, Kaur, Li, Loo, Matada, Roussel, Sahraei, Todaro, Vigbedor.
Vigbedor et al., 8 May 2021, peer-reviewed, 8 authors.
This PaperHCQAll
Review of four major biomolecular target sites for COVID-19 and possible inhibitors as treatment interventions
Vigbedor Bright, Tettey Clement Okraku, Essuman Edward Ken, Kyere Isaac, Aniagyei Albert, Kortei Nii Korley, Boakye Adjoa Agyemang, Osei-Owusu Jonathan
Journal of Applied Pharmaceutical Science, doi:10.7324/japs.2021.110825
This paper focuses on the review of major target sites in both the host organism and the severe acute respiratory syndrome coronavirus 2 virus and the inhibitors that have been screened so far to unravel possible treatment agents. In this review, four major target sites were found to be the main sites where the design of possible inhibitors and treatment interventions could be probed. The four major sites that were reviewed include main protease, transmembrane protease, serine 2, RNA-dependent RNA polymerase, and angiotensin-converting enzyme 2. Several existing drug candidates have been screened as inhibitors of the reviewed target sites and could serve as lead agents, prodrugs, and prospects for the treatment of coronavirus disease 2019. In this review, several inhibitors such as chloroquine (CQ) and hydroxychloroquine have gone through the clinical trial phase and are being utilized for the management of the disease. Drug candidates such as CQ, derivatives, remdesivir, and favipiravir have been used for the treatment of infected persons with 100% recovery rate. It is, therefore, imperative that further structural activity relationship and modifications be carried out using these drug candidates as models for synthesizing new analogues as treatment options.
AUTHORS' CONTRIBUTIONS Vigbedor, B.Y. drafted the manuscript and was in charge of the supervision. Tettey, C.O., Essuman, E. K., and Kortei, N.K. drafted the manuscript. Osei-Owusu, J., Aniagyei, A., Kyere, I., and Boakye, A. A. conducted a critical revision of the manuscript. CONFLICT OF INTEREST The authors report no financial or any other conflicts of interest in this work. FUNDING The authors received no funding for the study. ETHICAL APPROVALS Not Applicable. PUBLISHER'S NOTE This journal remains neutral with regard to jurisdictional claims in published institutional affiliation.
References
Biorxiv ; Wu, Liu, Yang, Zhang, Zhong et al., Review of four major biomolecular target sites for COVID-19 and possible inhibitors as treatment interventions
Cheng, Zhang, Xie, Jiang, Arnold et al., Chemical-informatics approach to COVID-19 drug discovery: Exploration of important fragments and data mining-based prediction of some hits from natural origins as main protease (Mpro) inhibitors, Journal of Molecular Structure
Goor, Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis, J Pathol
Hoffmann, Kleine-Weber, Schroeder, Krüger, Herrler et al., SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor, Cell
Kaufmann, Mcelrath, Lewis, Giudice, Letko et al., Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro
Verma, Kapoor, Das, Thakur, Potential inhibitors of SARS-CoV-2 main protease (Mpro) identified from the library of FDA approved drugs using molecular docking studies, Preprints, doi:10.20944/preprints202004.0149.v1WHO(2021).Covid19globalsituation
Vigbedor, None, Journal of Applied Pharmaceutical Science
Wong, Cregeen, Ajami, Petrosino, Evidence of recombination in coronaviruses implicating pangolin origins of nCoV
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