Novel adenosine derivatives against SARS-CoV-2 RNA-dependent RNA polymerase: an in silico perspective.
Pharmacol Rep
; 73(6): 1754-1764, 2021 Dec.
Article
in English
| MEDLINE | ID: covidwho-1283833
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.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Drug Design
/
Adenosine
/
Adenosine Monophosphate
/
Alanine
/
Coronavirus RNA-Dependent RNA Polymerase
Type of study:
Prognostic study
Limits:
Humans
Language:
English
Journal:
Pharmacol Rep
Journal subject:
Pharmacology
Year:
2021
Document Type:
Article
Affiliation country:
S43440-021-00300-9
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