SARS-CoV-2 Viroporins: A Multi-Omics Insight from Nucleotides to Amino Acids

Abstract

COVID-19 is caused by SARS-CoV-2 which has so far affected more than 500 million people worldwide and killed over 6 million as of 1 May 2022. The approved emergency-use vaccines were lifesaving in such a devastating pandemic. Inflammation-related pathways have been well documented to be upregulated in the case of SARS-CoV-2 in rodents, non-human primates and human samples. We reanalysed a previously published dataset to understand if certain molecular components of inflammation could be higher in infected samples. Mechanistically, viroporins are important players in the life cycle of SARS-CoV-2 and are primary to its pathogenesis. We studied the two prominent viroporins of SARS-CoV-2 (i) Orf3a and (ii) envelope (E) protein from a sequence and structural point of view. Orf3a is a cation-selective viral ion channel which has been shown to disrupt the endosomal pathways. E protein is one of the most conserved proteins among the SARS-CoV proteome which affects the ERGIC-related pathways. The aqueous medium through the viroporins mediates the non-selective translocation of cations, affecting ionic homeostasis in the host cellular compartments. We hypothesize a possible mechanistic approach whereby the ionic imbalance caused by viroporin action could potentially be one of the major pathogenic drivers leading to the increased inflammatory response in the host cell. Our results shed light into the transcriptomic, genomic and structural proteomics aspects of widely studied SARS-CoV-2 viroporins, which can be potentially leveraged for the development of antiviral therapeutics.