4.6 Article

Covalent Inhibitors from Saudi Medicinal Plants Target RNA-Dependent RNA Polymerase (RdRp) of SARS-CoV-2

Journal

VIRUSES-BASEL
Volume 15, Issue 11, Pages -

Publisher

MDPI
DOI: 10.3390/v15112175

Keywords

SARS-CoV-2; COVID-19; medicinal plants; RdRp; docking; MD simulation; phytochemicals

Categories

Ask authors/readers for more resources

COVID-19, caused by SARS-CoV-2, has caused significant loss of life. In the search for solutions, the researchers evaluated the inhibitory effects of ten phytochemicals isolated from Saudi medicinal plants on the RNA-dependent RNA polymerase (RdRp) of the virus. Compounds 7, 8, and 9 demonstrated non-nucleoside and irreversible interaction capabilities with RdRp, suggesting their potential as antivirals against SARS-CoV-2.
COVID-19, a disease caused by SARS-CoV-2, has caused a huge loss of human life, and the number of deaths is still continuing. Despite the lack of repurposed drugs and vaccines, the search for potential small molecules to inhibit SARS-CoV-2 is in demand. Hence, we relied on the drug-like characters of ten phytochemicals (compounds 1-10) that were previously isolated and purified by our research team from Saudi medicinal plants. We computationally evaluated the inhibition of RNA-dependent RNA polymerase (RdRp) by compounds 1-10. Non-covalent (reversible) docking of compounds 1-10 with RdRp led to the formation of a hydrogen bond with template primer nucleotides (A and U) and key amino acid residues (ASP623, LYS545, ARG555, ASN691, SER682, and ARG553) in its active pocket. Covalent (irreversible) docking revealed that compounds 7, 8, and 9 exhibited their irreversible nature of binding with CYS813, a crucial amino acid in the palm domain of RdRP. Molecular dynamic (MD) simulation analysis by RMSD, RMSF, and Rg parameters affirmed that RdRP complexes with compounds 7, 8, and 9 were stable and showed less deviation. Our data provide novel information on compounds 7, 8, and 9 that demonstrated their non-nucleoside and irreversible interaction capabilities to inhibit RdRp and shed new scaffolds as antivirals against SARS-CoV-2.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available