Repurposing FDA approved drugs against monkeypox virus DNA dependent RNA polymerase: virtual screening, normal mode...

Area of Science:

• Virology
• Drug Discovery
• Computational Chemistry

Background:

• Monkeypox disease, caused by the monkeypox virus, is a growing global health concern.
• There is currently no specific small molecule antiviral drug available for treating monkeypox.

Purpose of the Study:

• To identify potential drug candidates for monkeypox by repurposing FDA-approved drugs.
• To evaluate the efficacy of these drugs against the monkeypox virus DNA dependent RNA polymerase subunit A6R.

Main Methods:

• Virtual screening of 1615 FDA-approved drugs against the A6R protein.
• Normal mode analysis and molecular dynamics simulations to assess protein-drug complex stability.
• Analysis of binding interactions, including hydrogen bonds and hydrophobic interactions.

Main Results:

• Nilotinib, Conivaptan, and Ponatinib were identified as potent inhibitors of the A6R protein.
• These drugs exhibited strong binding energies (up to -7.5 kcal/mol) and formed stable interactions with key active site residues.
• Molecular dynamics simulations confirmed the stability of the identified drug-protein complexes.

Conclusions:

• Nilotinib, Conivaptan, and Ponatinib represent promising candidates for monkeypox treatment.
• Further experimental validation and clinical trials are warranted to confirm their antiviral activity.
• This study provides a foundation for repurposing compounds against highly pathogenic viruses.