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