Sars-Cov-2 Helicase Might Interfere With Cellular Nonsense-Mediated Rna Decay: Insights From a Bioinformatics Study Publisher Pubmed



Akbari B¹ ; Ahmadi E¹ ; Zabihi MR¹ ; Zamir MR¹ ; Shaker MS¹ ; Noorbakhsh F^{1, 2} Show Affiliations
Source: BMC Genomic Data Published:2023

Abstract

Background: Viruses employ diverse strategies to interfere with host defense mechanisms, including the production of proteins that mimic or resemble host proteins. This study aimed to analyze the similarities between SARS-CoV-2 and human proteins, investigate their impact on virus-host interactions, and elucidate underlying mechanisms. Results: Comparing the proteins of SARS-CoV-2 with human and mammalian proteins revealed sequence and structural similarities between viral helicase with human UPF1. The latter is a protein that is involved in nonsense-mediated RNA decay (NMD), an mRNA surveillance pathway which also acts as a cellular defense mechanism against viruses. Protein sequence similarities were also observed between viral nsp3 and human Poly ADP-ribose polymerase (PARP) family of proteins. Gene set enrichment analysis on transcriptomic data derived from SARS-CoV-2 positive samples illustrated the enrichment of genes belonging to the NMD pathway compared with control samples. Moreover, comparing transcriptomic data from SARS-CoV-2-infected samples with transcriptomic data derived from UPF1 knockdown cells demonstrated a significant overlap between datasets. Conclusions: These findings suggest that helicase/UPF1 sequence and structural similarity might have the ability to interfere with the NMD pathway with pathogenic and immunological implications. © 2023, The Author(s).