Inhibition of Chikungunya virus nsP2 protease in vitro by pantinin-1 isolated from scorpion venom

Climate change has enhanced the spread of arboviruses such as Chikungunya virus (CHIKV). CHIKV is a re-emerging virus from the family Togaviridae that has spread globally, causing numerous outbreaks. The lack of antiviral therapy against CHIKV makes it a significant threat to public health. Cleavage of the viral polyprotein depends on the catalytic activity of nsP2, which is essential for viral replication. Due to this critical role, the nsP2 protease is a promising target for antiviral drug development. Animal venom-derived peptides have shown great potential against a variety of diseases, including infections, cancer, and neurodegenerative disorders. In this study, we evaluated the inhibitory effects and properties of pantinin-1, a peptide derived from the scorpion Pandinus imperator with broad antimicrobial activity, against CHIKV nsP2 protease. Pantinin-1 effectively inhibited CHIKV nsP2 protease, with a half-maximal inhibitory concentration (IC50) of 6.4 {+/-} 2.04 {micro}M and complete inhibition at 175 {micro}M. Further analysis revealed that pantinin-1 acts as a competitive inhibitor with low micromolar affinity and showed no toxicity up to 20 {micro}M in cell culture. Lastly, using molecular docking with subsequent molecular dynamics, the protein-peptide interaction was analyzed, and the key residues involved in the interaction with the protease were predicted. These findings highlight the potential inhibitory effect of pantinin-1 as a lead candidate targeting nsP2 protease.