In Silico high-throughput virtual screening and molecular dynamics simulation study to identify 3CLpro inhibitor of COVID-19
Amreesh Parvez, Sunita Kumari Yadav, Vivek Parashar Pandey, Xianghui Qi · 2020
Abstract COVID-19 is an ongoing coronavirus pandemic with more than 260,000 deaths worldwide so far. In the event of no targeted drug and vaccine for SARS-CoV-2, causative agent of COVID-19, finding newer targets becomes indispensable. 3CLpro is a processing enzyme of viral replicase-transcriptase complex, chosen as a potential drug target. 3CLpro of COVID-19 is structurally similar to SARS-CoV and MERS-CoV 3CLpro. Here, we built up an in-house inhibitor library for 3CLpro of SARS-CoV and MERS-CoV. The library revealed 7 non-toxic compounds with 5 compounds showing significant protease and enzyme inhibition activity. Molecular docking of these compounds with 3CLpro shown lower binding energy profile of compounds 1 and 2. The compactness and flexibility analysis of compounds 1 and 2 complexes with 3CLpro showed lower stability profile as compared to unbound 3CLpro. The results cite the potential of compounds 1 and 2 as probable inhibitors of 3CLpro as a prospective therapeutic target for COVID-19.