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.]
|Original language||English (US)|
|State||Published - 2021|
Bibliographical noteKAUST Repository Item: Exported on 2021-09-09
Acknowledgements: Shaheen supercomputer of King Abdullah University of Science and Technology (KAUST) is used to perform the after dockings MDS calculations (under Project Number k1482). In addition, the Bibliotheca Alexandrina is used to perform the initial MDS calculations. This work is supported by the Cairo University COVID-19 fund received by AAE.
This publication acknowledges KAUST support, but has no KAUST affiliated authors.