Binding Mechanism and Structural Insights into the Identified Protein Target of Covid-19 with In-Vitro Effective Drug Ivermectin

Parth Sarthi Sen Gupta, Satyaranjan Biswal, Saroj Kumar Panda, Abhik Kumar Ray, Malay Kumar Rana

10.26434/chemrxiv.12463946.v1

Research curated

Abstract

While an FDA approved drug Ivermectin was reported to dramatically reduce the cell line of SARS-CoV-2 by ~5000 folds within 48 hours, the precise mechanism of action and the COVID-19 molecular target involved in interaction with this in-vitro effective drug are unknown yet. Among 12 different COVID-19 targets studied here, the RNA dependent RNA polymerase (RdRp) with RNA and Helicase NCB site show the strongest affinity to Ivermectin amounting -10.4 kcal/mol and -9.6 kcal/mol, respectively. Molecular dynamics of corresponding protein-drug complexes reveals that the drug bound state of RdRp with RNA has better structural stability than the Helicase NCB site, with MM/PBSA free energy of -135.2 kJ/mol, almost twice that of Helicase (-76.6 kJ/mol). The selectivity of Ivermectin to RdRp is triggered by a cooperative interaction of RNA-RdRp by ternary complex formation. Identification of the target and its interaction profile with Ivermectin can lead to more powerful drug designs for COVID-19 and experimental exploration.

Source: ChemRxiv

Related molecules

Name	Synonyms	Genes
Helicase	Helicase, nsp13, Hel, p66, p66-HEL, Non-structural protein 13	rep, ORF1a-1b
RNA dependent RNA polymerase	RDR, viral RNA polymerase, RdRp, nsp12	rep, ORF1a-1b, RdRp
Ivermectin	IVERMECTIN, Ivermectin B1a, Dihydroavermectin B1a, 70288-86-7, 22-23-Dihydroavermectin B1a

Related interactions

Target	Drug	Type	Result
Helicase	Ivermectin	Computational	positive
RNA dependent RNA polymerase	Ivermectin	Computational	positive