Sen Liu1,2, Qiang Zheng1,2, Zhiying Wang1,2. 1. National '111' Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Industrial Fermentation (Ministry of Education). 2. Institute of Biomedical and Pharmaceutical Sciences, Hubei Key Laboratory of Industrial Microbiology, School of Food and Biological Engineering, Hubei University of Technology, Wuhan 430068, China.
Abstract
MOTIVATION: Since December 2019, the newly identified coronavirus SARS-CoV-2 has caused a massive health crisis worldwide and resulted in over 70 000 COVID-19 infections so far. Clinical drugs targeting SARS-CoV-2 are urgently needed to decrease the high fatality rate of confirmed COVID-19 patients. Traditional de novo drug discovery needs more than 10 years, so drug repurposing seems the best option currently to find potential drugs for treating COVID-19. RESULTS: Compared with traditional non-covalent drugs, covalent drugs have attracted escalating attention recent years due to their advantages in potential specificity upon careful design, efficiency and patient burden. We recently developed a computational protocol named as SCAR (steric-clashes alleviating receptors) for discovering covalent drugs. In this work, we used the SCAR protocol to identify possible covalent drugs (approved or clinically tested) targeting the main protease (3CLpro) of SARS-CoV-2. We identified 11 potential hits, among which at least six hits were exclusively enriched by the SCAR protocol. Since the preclinical or clinical information of these identified drugs is already available, they might be ready for being clinically tested in the treatment of COVID-19. CONTACT: senliu.ctgu@gmail.com.
MOTIVATION: Since December 2019, the newly identified coronavirusSARS-CoV-2 has caused a massive health crisis worldwide and resulted in over 70 000 COVID-19infections so far. Clinical drugs targeting SARS-CoV-2 are urgently needed to decrease the high fatality rate of confirmed COVID-19patients. Traditional de novo drug discovery needs more than 10 years, so drug repurposing seems the best option currently to find potential drugs for treating COVID-19. RESULTS: Compared with traditional non-covalent drugs, covalent drugs have attracted escalating attention recent years due to their advantages in potential specificity upon careful design, efficiency and patient burden. We recently developed a computational protocol named as SCAR (steric-clashes alleviating receptors) for discovering covalent drugs. In this work, we used the SCAR protocol to identify possible covalent drugs (approved or clinically tested) targeting the main protease (3CLpro) of SARS-CoV-2. We identified 11 potential hits, among which at least six hits were exclusively enriched by the SCAR protocol. Since the preclinical or clinical information of these identified drugs is already available, they might be ready for being clinically tested in the treatment of COVID-19. CONTACT: senliu.ctgu@gmail.com.
Authors: Jackson L Amaral; Jose T A Oliveira; Francisco E S Lopes; Cleverson D T Freitas; Valder N Freire; Leonardo V Abreu; Pedro F N Souza Journal: J Biomol Struct Dyn Date: 2021-05-05