Innovative, rapid, high-throughput method for drug repurposing in a pandemic—A case study of SARS-CoV-2 and COVID-19

Frontiers in Pharmacology

Pharmacology

Mustapha Umar Imam¹  Abdulmalik Shuaibu²  Muhammad Bashir Bello²  Aishatu Yahaya Bello³  Adamu Ahmed Adamu⁴  Abdulmajeed Yunusa⁴  Shaibu Oricha Bello⁵  Mustapha Ayodele Popoola⁶  Zaiyad Garba Habib⁷  Yusuf Yahaya Deeni⁸  Chinwe Lucia Ochu⁹  Ehimario Uche Igumbor^1,10  Ifeoma Okoye^1,11 

[1] Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, Sokoto, Nigeria;Department of Medical Biochemistry, Usmanu Danfodiyo University, Sokoto, Nigeria;Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, Sokoto, Nigeria;Department of veterinary Microbiology, Usmanu Danfodiyo University, Sokoto, Nigeria;Department of Clinical pharmacy and Pharmacy Practice, Faculty of Pharmaceutical sciences, Usmanu Danfodiyo University, Sokoto, Nigeria;Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto, Nigeria;Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, Sokoto, Nigeria;Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto, Nigeria;Nigerian COVID-19 Research Coalition, Nigerian Institute of Medical Research Institute, Abuja, Nigeria;Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, Sokoto, Nigeria;Nigerian COVID-19 Research Coalition, Nigerian Institute of Medical Research Institute, Abuja, Nigeria;Nigerian COVID-19 Research Coalition, Nigerian Institute of Medical Research Institute, Abuja, Nigeria;Department of Medicine, University of Abuja Teaching Hospital, Gwagwalada, Abuja, Nigeria;Nigerian COVID-19 Research Coalition, Nigerian Institute of Medical Research Institute, Abuja, Nigeria;Department of Microbiology and Biotechnology, Federal University of Dutse, Dutse, Nigeria;Centre for Environmental and Public Health Research and Development, Kano, Nigeria;Nigerian COVID-19 Research Coalition, Nigerian Institute of Medical Research Institute, Abuja, Nigeria;Nigerian Centre for Disease Control and Prevention, Abuja, Nigeria;Nigerian COVID-19 Research Coalition, Nigerian Institute of Medical Research Institute, Abuja, Nigeria;School of Public Health, University of the Western Cape, Cape Town, South Africa;University of Nigeria Centre for Clinical Trials, University of Nigeria Teaching Hospital, Enugu, Ituku Ozalla, Nigeria;

关键词: SARS-CoV-2;    COVID-19 treatment;    repurpose;    cytopathic action;    docking & simulation;   

DOI  :  10.3389/fphar.2023.1130828

 received in 2022-12-23, accepted in 2023-02-20,  发布年份 2023

来源: Frontiers

【 摘 要 】

Several efforts to repurpose drugs for COVID-19 treatment have largely either failed to identify a suitable agent or agents identified did not translate to clinical use. Reasons that have been suggested to explain the failures include use of inappropriate doses, that are not clinically achievable, in the screening experiments, and the use of inappropriate pre-clinical laboratory surrogates to predict efficacy. In this study, we used an innovative algorithm, that incorporates dissemination and implementation considerations, to identify potential drugs for COVID-19 using iterative computational and wet laboratory methods. The drugs were screened at doses that are known to be achievable in humans. Furthermore, inhibition of viral induced cytopathic effect (CPE) was used as the laboratory surrogate to predict efficacy. Erythromycin, pyridoxine, folic acid and retapamulin were found to inhibit SARS-CoV-2 induced CPE in Vero cells at concentrations that are clinically achievable. Additional studies may be required to further characterize the inhibitions of CPE and the possible mechanisms.

【 授权许可】

Unknown   
Copyright © 2023 Bello, Yunusa, Adamu, Imam, Bello, Shuaibu, Igumbor, Habib, Popoola, Ochu, Bello, Deeni and Okoye.