Abstract
Since the beginning of the COVID-19 pandemic, scientists across the globe are racing to find a cure for the highly contagious infectious disease caused by the SARS-CoV-2 virus. Despite many promising ongoing progress, there are currently no FDA approved drug to treat infected patients. Recently, the crowdsourcing of drug discovery for inhibiting the main protease (Mpro) of SARS-CoV-2 have yielded a plenty of drug fragments resolved inside the active site of Mpro via the crystallography method. Following the principle of fragment-based drug design (FBDD), we are motivated to design a potent drug candidate (named B19) by merging three fragments JFM, U0P, and HWH. Through extensive all-atom molecular dynamics simulation and molecular docking, we found that B19 among all designed ones is most stable inside the Mpro’s active site and the binding free energy of B19 is comparable to or even a little better than that of a native protein ligand processed by Mpro. Our promising results suggest that B19 and its derivatives can potentially be efficacious drug candidates for COVID-19.
Keywords: COVID-19; SARS-CoV-2; fragment-based drug design; main protease.
【저자키워드】 COVID-19, SARS-CoV-2, main protease, fragment-based drug design, 【초록키워드】 Drug discovery, drug design, COVID-19 pandemic, molecular docking, SARS-CoV-2 virus, Infectious disease, molecular dynamics, protease, FDA, binding free energy, Molecular dynamics simulation, free energy, MPro, Protein, Ligand, cure, active site, infected patients, principle, fragment, treat, drug candidate, derivative, contagious, caused, globe, approved, comparable, inhibiting, processed, resolved, the SARS-CoV-2 virus, 【제목키워드】 drug, inhibiting,