AUTHOR=Tasneem Alvea , Sultan Armiya , Singh Prithvi , Bairagya Hridoy R. , Almasoudi Hassan Hussain , Alhazmi Abdulfattah Yahya M. , Binshaya Abdulkarim S. , Hakami Mohammed Ageeli , Alotaibi Bader S. , Abdulaziz Eisa Alaa , Alolaiqy Abdulaziz Saleh I. , Hasan Mohammad Raghibul , Dev Kapil , Dohare Ravins 

TITLE=Identification of potential therapeutic targets for COVID-19 through a structural-based similarity approach between SARS-CoV-2 and its human host proteins

JOURNAL=Frontiers in Genetics

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2024.1292280

DOI=10.3389/fgene.2024.1292280

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> The COVID-19 pandemic caused by SARS-CoV-2 has led to millions of deaths worldwide, and vaccination efficacy has been decreasing with each lineage, necessitating the need for alternative antiviral therapies. Predicting host–virus protein–protein interactions (HV-PPIs) is essential for identifying potential host-targeting drug targets against SARS-CoV-2 infection.</p><p><bold>Objective:</bold> This study aims to identify therapeutic target proteins in humans that could act as virus–host-targeting drug targets against SARS-CoV-2 and study their interaction against antiviral inhibitors.</p><p><bold>Methods:</bold> A structure-based similarity approach was used to predict human proteins similar to SARS-CoV-2 (“hCoV-2”), followed by identifying PPIs between hCoV-2 and its target human proteins. Overlapping genes were identified between the protein-coding genes of the target and COVID-19-infected patient’s mRNA expression data. Pathway and Gene Ontology (GO) term analyses, the construction of PPI networks, and the detection of hub gene modules were performed. Structure-based virtual screening with antiviral compounds was performed to identify potential hits against target gene-encoded protein.</p><p><bold>Results:</bold> This study predicted 19,051 unique target human proteins that interact with hCoV-2, and compared to the microarray dataset, 1,120 target and infected group differentially expressed genes (TIG-DEGs) were identified. The significant pathway and GO enrichment analyses revealed the involvement of these genes in several biological processes and molecular functions. PPI network analysis identified a significant hub gene with maximum neighboring partners. Virtual screening analysis identified three potential antiviral compounds against the target gene-encoded protein.</p><p><bold>Conclusion:</bold> This study provides potential targets for host-targeting drug development against SARS-CoV-2 infection, and further experimental validation of the target protein is required for pharmaceutical intervention.</p>