Network‐Based Drug Repurposing and Genomic Analysis to Unveil Potential Therapeutics for Monkeypox Virus

Abstract The emergence of the human monkeypox virus (MPXV) and the lack of effective medications have necessitated the exploration of various strategies to combat its infection. This study employs a network‐based approach to drug discovery, utilizing the BLASTn and phylogenetic analysis to compare the MPXV genome with those of 18 related orthopoxviruses, revealing over 75 % genomic similarity. Through a literature review, 160 human‐host proteins linked to MPXV and its relatives were identified, leading to the construction of a human‐host protein interactome. Analysis of this interactome highlighted 39 central hub proteins, which were then examined for potential drug targets. The process successfully revealed 15 targets already approved for use with medications. Additionally, the functional enrichment analysis provided insights into potential pathways and disorders connected with these targets. Four medications, namely Baricitinib, Infliximab, Adalimumab, and Etanercept, have been identified as potential candidates for repurposing to combat MPXV. In addition, the pharmacophore‐based screening identified a molecule that is comparable to Baricitinib and has the potential to be effective against MPXV. The findings of the study suggest that ZINC22060520 is a promising medication for treating MPXV infection and proposes these medications as potential options for additional experimental and clinical assessment in the battle against MPXV.