Affiliation:
1. Department of Biophysics, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India
Abstract
The 2019 coronavirus pandemic prompted extensive research into the molecular composition of the virus. The SARS-CoV-2 virus contains small noncoding RNAs (sNCR, miRNAs) targeting crucial host genes. This study identified 24 potential precursor and mature Viral-miRNAs (V-miRNAs) in the SARS-CoV-2 genome with favorable thermodynamic energies associated with 1883 human genes, 334 of which are involved in the COVID-19 infection. Out of 24, 14 predicted mature SARS-CoV-2 V-miRNAs target 28 host genes of the 334 genes involved in COVID-19 based on their robust molecular hybridization (thermodynamic stability, canonical base pairing, minimal noncanonical base pairs, loops, and bulges). Eight of the 14 mature V-miRNAs showed sequence conservancy with other organisms based on predicted 3D structures. Gene ontology enrichment analysis revealed these 28 host genes are involved in 42 biological processes, 4 cellular components, and 10 molecular processes. Further, the 14 predicted mature V-miRNAs were screened against FDA-approved (COVID-19 drug dataset) to identify the top best-hit compounds, which include Bemcentinib and Zavegepant. These two drugs show strong binding affinities ([Formula: see text]9.2 to −12.4 kcal/mol) with 13 and 12 predicted mature V-miRNAs, respectively. Furthermore, molecular docking of V-miRs-host AGO protein interactions suggested strong binding affinities and extensive hydrogen bonding interactions between V-miRNAs and the host AGO protein (involved in miRNA biogenesis and mRNA regulation). These findings suggest a potential regulatory role of Bemcentinib and Zavegepant through strong binding interaction with various V-miRNAs and in modulating host gene expression through their interactions with the AGO protein.
Publisher
World Scientific Pub Co Pte Ltd
Subject
Computational Theory and Mathematics,Physical and Theoretical Chemistry,Computer Science Applications