Repurposing FDA approved drugs against monkeypox virus DNA dependent RNA polymerase: virtual screening, normal mode analysis and molecular dynamics simulation studies.

Zoonotic monkeypox disease, caused by the double-stranded DNA monkeypox virus, has become a global concern. Due to the absence of a specific small molecule drug for the disease, this report aims to identify potential inhibitor drugs for monkeypox. This study explores a drug repurposing strategy using virtual screening to evaluate 1615 FDA approved drugs against the monkeypox virus DNA dependent RNA polymerase subunit A6R. Normal mode analysis and molecular dynamics simulation assessed the flexibility and stability of the target protein in complex with the top screened drugs. The analysis identified Nilotinib (ZINC000006716957), Conivaptan (ZINC000012503187), and Ponatinib (ZINC000036701290) as the most potential RNA polymerase inhibitors with binding energies of - 7.5 kcal/mol. These drugs mainly established hydrogen bonds and hydrophobic interactions with the protein active sites, including LEU95, LEU90, PRO96, MET110, and VAL113, and residues nearby. Normal mode analysis and molecular dynamics simulation confirmed the stability of interactions between the top drugs and the protein. In conclusion, we have discovered promising drugs that can potentially control the monkeypox virus and should be further explored through experimental assays and clinical trials to assess their actual activity against the disease. The findings of this study could lay the foundation for screening repurposed compounds as possible antiviral treatments against various highly pathogenic viruses.