| Summary: | SARS-CoV-2 is a novel coronavirus that replicates itself via interacting with the host proteins. As a result, identifying virus and host protein-protein interactions could help researchers better understand the virus disease transmission behavior and identify possible COVID-19 drugs. The International Committee on Virus Taxonomy has determined that nCoV is genetically 89% compared to the SARS-CoV epidemic in 2003. This paper focuses on assessing the host–pathogen protein interaction affinity of the coronavirus family, having 44 different variants. In light of these considerations, a GO-semantic scoring function is provided based on Gene Ontology (GO) graphs for determining the binding affinity of any two proteins at the organism level. Based on the availability of the GO annotation of the proteins, 11 viral variants, <i>viz.</i>, SARS-CoV-2, SARS, MERS, <i>Bat coronavirus</i> HKU3, <i>Bat coronavirus</i> Rp3/2004, <i>Bat coronavirus</i> HKU5, <i>Murine coronavirus</i>, <i>Bovine coronavirus</i>, Rat coronavirus, <i>Bat coronavirus</i> HKU4, <i>Bat coronavirus</i> 133/2005, are considered from 44 viral variants. The fuzzy scoring function of the entire host–pathogen network has been processed with ~180 million potential interactions generated from 19,281 host proteins and around 242 viral proteins. ~4.5 million potential level one host–pathogen interactions are computed based on the estimated interaction affinity threshold. The resulting host–pathogen interactome is also validated with <i>state-of-the-art</i> experimental networks. The study has also been extended further toward the drug-repurposing study by analyzing the FDA-listed COVID drugs.
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