Computational investigation of antiviral peptide interactions with Mpox DNA polymerase.

Abstract

The Mpox DNA polymerase (DNA pol) plays a crucial role in the viral replication process, making it an ideal target for antiviral therapies. It facilitates the synthetic process of viral DNA, which is an integral stage in the life of a virus. The inhibition of the operation of Mpox DNA pol would interfere with the multiplication of the virus and help manage the disease. Peptides have emerged as a possible therapeutic alternative against viruses due to their distinct characteristics. Peptides have broad-spectrum antiviral activity, being effective against a variety of viruses. Using computational techniques, we attempted to explore the molecular details of the interaction between antiviral peptides and Mpox DNA pol. Two databases of antiviral peptides were screened in this study. This study used molecular docking, followed by molecular dynamics (MD) simulation and post-simulation binding energy predictions. From the 19 selected peptides with activity against DNA polymerases, two peptides-DRAVPe01393 and DRAVPe01399-were identified as particularly promising candidates. These peptides exhibited stable interactions with Mpox DNA pol and demonstrated good cell penetration potential as evident from the MD simulation studies. Notably, the peptides DRAVPe01399 and DRAVPe01393 have a better binding affinity of - 60.86 kcal/mol and - 47.92 kcal/mol respectively than the control ligand Cidofovir diphosphate (- 10.79 kcal/mol). These findings could lead to the development of innovative antiviral treatments to prevent monkeypox, helping global efforts to battle this emerging infectious disease.