SARS-CoV-2 Helicase might interfere with cellular nonsense-mediated RNA decay, insights from a bioinformatics study

Abstract

Unraveling molecular interactions between viral proteins and host cells is key to understanding the pathogenesis of viral diseases. We hypothesized that potential sequence and structural similarities between SARS-CoV2 proteins and proteins of infected cells might influence host cell biology and antiviral defense. 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-CoV2-infected samples with transcriptomic data derived from UPF1 knockout cells demonstrated a significant overlap between datasets. 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.