Novel adenosine derivatives against SARS-CoV-2 RNA-dependent RNA polymerase: an in silico perspective

Abstract

Background: SARS-CoV-2 is a newly emerged human coronavirus that severely affected human health and the economy. The viral RNA-dependent RNA polymerase (RdRp) is a crucial protein target to stop virus replication. The adenosine derivative, remdesivir, was authorized for emergency use 10 months ago by the United States FDA against COVID-19 despite its doubtful efficacy against SARS-CoV-2. Methods: A dozen modifications based on remdesivir are tested against SARS-CoV-2 RdRp using combined molecular docking and dynamics simulation in this work. Results: The results reveal a better binding affinity of 11 modifications compared to remdesivir. Compounds 8, 9, 10, and 11 show the best binding affinities against SARS-CoV-2 RdRp conformations gathered during 100 ns of the Molecular Dynamics Simulation (MDS) run (− 8.13 ± 0.45 kcal/mol, − 8.09 ± 0.67 kcal/mol, − 8.09 ± 0.64 kcal/mol, and − 8.07 ± 0.73 kcal/mol, respectively). Conclusions: The present study suggests these four compounds as potential SARS-CoV-2 RdRp inhibitors, which need to be validated experimentally. Graphic abstract: [Figure not available: see fulltext.].