Candidate inhibitors of SARS-CoV-2 main protease with 3D structures similar to N3

Coronavirus disease 2019 caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) has become pandemic. SARS-CoV-2 causes influenza-like illnesses, respiratory symptoms, serious lung injuries, pneumonia, multi-organ damage, and mortality. The genome of coronaviruses contains approximately six open reading frames (ORFs). ORF 1a/b is translated into protein phosphatases 1a and 1ab, which are processed by SARS-CoV-2's main protease (M^pro). M^prois critical for viral gene expression and replication, making it a key drug target. The first 3D structure of Mpro in complex with an inhibitor N3 (PDB ID: 6LU7) was reported. This study aimed to screen for N3-like structures via the docking method as potent Mpro inhibitors and drug candidates. The M^pro-N3 complex (6LU7) was set up in the RCSB Protein Data Bank. N3 was expelled from the structure of M^prousing PyMol 2.3.4.0. Novel ligands from PubChem with structures similar to N3 were screened for docking by Pyrx 8.0 and envisioned by PyMol 2.3.4.0. Our research demonstrated that the binding affinity of CID 6476896 was the highest at -7.8 kcal/mol. However, only CIDs 7885280 and 6476893 were possible Mpro inhibitors that interacted with the substrate-binding pocket similarly to N3 and could be drug candidates to target the Mpro of SARS-CoV-2. © 2021 Elsevier B.V., All rights reserved.