Comparative genomics and integrated system biology approach unveiled undirected phylogeny patterns, mutational hotspots, functional patterns, and molecule repurposing for monkeypox virus

Monkeypox is a viral zoonosis with symptoms that are reminiscent of those experienced in previous smallpox cases. The GSAID database (Global Initiative on Sharing Avian Influenza Data) was used to assess 630 genomes of MPXV. The phylogenetic study revealed six primary clades, as well as a smaller percentage in radiating clades. Individual clades that make up various nationalities may have formed as a result of a particular SNP hotspot type that mutated in a specific population. The most significant mutation based on a mutational hotspot analysis was found at G3729A and G5143A. The gene ORF138, which encodes the Ankyrin repeat (ANK) protein, was found to have the most mutations. This protein mediates molecular recognition via protein–protein interactions. It was shown that 243 host proteins interacted with 10 monkeypox proteins identified as the hub proteins E3, SPI2, C5, K7, E8, G6, N2, B14, CRMB, and A41 through 262 direct connections. The interaction with chemokine system-related proteins provides further evidence that the monkeypox virus suppresses human proteins to facilitate its survival against innate immunity. Several FDA-approved molecules were evaluated as possible inhibitors of F13, a significant envelope protein on the membrane of extracellular versions of the virus. A total of 2500 putative ligands were individually docked with the F13 protein. The interaction between the F13 protein and these molecules may help prevent the monkeypox virus from spreading. After being confirmed by experiments, these putative inhibitors could have an impact on the activity of these proteins and be used in monkeypox treatments.