Repurposing of FDA-Approved Antiviral Drugs Against Monkeypox Virus: Comparative In Vitro Screening and Structure...

Area of Science:

• Virology
• Drug Discovery
• Computational Biology

Background:

• Monkeypox (MPXV) is a global health concern with no approved treatments for non-severe cases.
• Emerging MPXV strains show resistance to existing antivirals, necessitating novel therapeutic strategies.
• Drug repositioning offers a cost-effective approach to identify potential MPXV treatments.

Purpose of the Study:

• To evaluate the efficacy of FDA-approved antiviral drugs against MPXV using a drug repositioning strategy.
• To identify potential drug targets within MPXV proteins through in silico analysis.

Main Methods:

• Screening of 23 FDA-approved antiviral drugs in vitro against an Egyptian MPXV strain.
• In silico molecular docking and dynamics simulations against MPXV Thymidylate Kinase, A42R Profilin-Like Protein, and VACV D13.
• Assessment of binding free energy for drug-protein interactions.

Main Results:

• Two antiviral drugs demonstrated in vitro activity against MPXV.
• Remdesivir exhibited superior binding affinity and stable complex formation with target MPXV proteins.
• Computational analysis revealed strong binding patterns for Remdesivir.

Conclusions:

• Remdesivir is a potent antiviral compound against the tested MPXV strain.
• Remdesivir's robust binding to MPXV Thymidylate Kinase, A42R Profilin-Like Protein, and VACV D13 supports its therapeutic potential.
• Remdesivir may be a viable option for treating monkeypox virus infections.