­ Poxviridae Protein kinases as targets for control of LSDV , Monkeypox like outbreaks

Lumpy skin disease virus has infected cows across the world resulting in the death or destruction of at least a million cows. Poxviridae family includes 88 such viruses that cause deadly diseases like smallpox, monkeypox and lumpy skin disease. Pox virus induced infections have been known to be sporadic and zoonotic. We identified two novel protein kinases in poxviridae genomes. Multiple sequence alignment and phylogenetic analysis of these pox viral protein kinases revealed the sequence conservation and evolutionary relationships of these viral protein kinases. AI driven methods revealed 3D structures and active site of the two protein kinases. The viral kinases also showed remarkable structural conservation. Virtual screening of pox virus kinases identified LSTK and LYK as druggable targets and 2 FDA approved kinase inhibitors (lapatinib and pazopanib) were recognized as potential inhibitors of LSTK and LYK. Molecular dynamics simulations identified these inhibitors to be competitive inhibitors of the new kinases. These findings provide valuable insights that can be leveraged in the development of antiviral therapeutics for pox virus infections LSDV and Monkeypox.