Ivermectin as a promising RNA-dependent RNA polymerase inhibitor and a therapeutic drug against SARS-CoV2: Evidence from in silico studies

strongerthrulife | 8 points | Sep 11 2020 00:22:45

Ivermectin as a promising RNA-dependent RNA polymerase inhibitor and a therapeutic drug against SARS-CoV2: Evidence from in silico studies

https://www.researchsquare.com/article/rs-73308/v1

[-] stereomatch | 2 points | Sep 12 2020 12:01:55

Methods: The 3D structure of ivermectin along with known antiviral drug lopinavir, simeprevir and four nucleotides ATP, GTP, CTP, and UTP were downloaded from PubChem database. Crystal structures of proteins were downloaded from PDB database. PDB files were converted into pdbqt file using AutoDock tools. After proper processing and grid formation, docking was carried out in AutoDock vina. Furthermore, the co-crystallized RNA and its binding interactions with RdRp were studied using various visualization tools including Discovery studio.

Results: Docking study showed that ivermectin is the best binding drug compared to lopinavir and simeprevir. The best binding interaction was found to be -9.7kcal/mol with RdRp suggesting potential inhibitor of the protein. Twenty-one amino acid residues of RdRp were found to interact with ivermectin including the catalytic residue Asp760. Furthermore, RNA-RdRp complex revealed that the catalytic active residues Ser759 and Asp760 of RdRp formed strong interactions with RNA chain. Binding of ivermectin in the active site of RdRp make clash with the nucleotides of RNA chain suggesting the possible inhibition of replication.

Conclusions: The present study suggests ivermectin as a potential inhibitor of RdRp which may be crucial to combat the SARS-CoV2.

[-] scionkia | 1 points | Sep 11 2020 12:49:18

Interesting.

[-] TrumpLyftAlles | 1 points | Sep 15 2020 20:21:31

Why does ivermectin (potentially) binding to RdRP matter?

Viral RNA-dependent RNA polymerases (RdRPs) play essential roles in viral genome replication and transcription.

https://www.pnas.org/content/113/28/E4005

The RNA-dependent RNA polymerase (RdRP), a viral enzyme for viral RNA replication in host cells, is one of the most intriguing and promising drug targets for SARS-CoV-2 drug development. Because RdRP is a viral enzyme with no host cell homologs, selective SARS-CoV-2 RdRP inhibitors can be developed that have improved potency and fewer off-target effects against human host proteins and thus are safer and more effective therapeutics for treating COVID-19.

https://journals.sagepub.com/doi/full/10.1177/2472555220942123