Potential covalent drugs targeting the main protease of the SARS-CoV-2 coronavirus

• DOI: 10.1093/bioinformatics/btaa224
• Publication Date: 2020-03-26T12:12:22Z
• Authors: Sen Liu; Qiang Zheng; Zhiying Wang
• Keywords: Statistics and Probability; 0303 health sciences; SARS-CoV-2; Pneumonia, Viral; COVID-19; Viral Nonstructural Proteins; Biochemistry; Computer Science Applications; 3. Good health; Coronavirus; Computational Mathematics; Betacoronavirus; Cysteine Endopeptidases; 03 medical and health sciences; Drug Delivery Systems; Computational Theory and Mathematics; Severe acute respiratory syndrome-related coronavirus; Humans; Coronavirus Infections; Molecular Biology; Pandemics; Coronavirus 3C Proteases; Peptide Hydrolases

AbstractMotivationSince 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.ResultsCompared 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 [e-mail]