Abstract
The Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) virus spread the novel CoronaVirus -19 (nCoV-19) pandemic, resulting in millions of fatalities globally. Recent research demonstrated that the Protein-Protein Interaction (PPI) between SARS-CoV-2 and human proteins is accountable for viral pathogenesis. However, many of these PPIs are poorly understood and unexplored, necessitating a more in-depth investigation to find latent yet critical interactions. This article elucidates the host-viral PPI through Machine Learning (ML) lenses and validates the biological significance of the same using web-based tools. ML classifiers are designed based on comprehensive datasets with five sequence-based features of human proteins, namely Amino Acid Composition, Pseudo Amino Acid Composition, Conjoint Triad, Dipeptide Composition, and Normalized Auto Correlation. A majority voting rule-based ensemble method composed of the Random Forest Model (RFM), AdaBoost, and Bagging technique is proposed that delivers encouraging statistical performance compared to other models employed in this work. The proposed ensemble model predicted a total of 111 possible SARS-CoV-2 human target proteins with a high likelihood factor ≥70%, validated by utilizing Gene Ontology (GO) and KEGG pathway enrichment analysis. Consequently, this research can aid in a deeper understanding of the molecular mechanisms underlying viral pathogenesis and provide clues for developing more efficient anti-COVID medications.