Computational Approaches in Targeting Monkeypox Virus: A Focus on Phytochemical Inhibition of Profilin-like Protein A42R

Monkeypox, a viral infection caused by the Monkeypox virus (MPXV), poses a significant public health threat. To identify potential antiviral metabolites against MPXV, we focused on the monkeypox profilin-like protein, crucial for viral replication. Twenty metabolites from various classes were retrieved from PubChem for molecular dynamics simulations. The top three molecules—Melongoside N, CID-4483043, Avenacosid A, CID-267363, and Melongoside P, CID- 131750951 demonstrated the best binding affinity for Profilin-like Protein A42R (PDB-4QWO). These ligands displayed stable interactions and minimal structural fluctuations during simulations, as indicated by favorable RMSD, RMSF, Rg, SASA, MolSA, and PSA results. The ligands maintained acceptable conformational stability with RMSD values within 1–3 Å, showing minimal structural changes. The ligands exhibited stable interactions with specific protein residues, indicating consistent and limited local alterations in the protein structure. Throughout a 250 ns simulation, the ligands maintained the protein's compactness, with average Rg values suggesting no major structural changes. Ligand complexes displayed typical van der Waals surface areas and polar interactions, supporting their stable interaction with the target protein. These ligands show promise as antiviral agents against monkeypox, with in-silico findings providing valuable insights for drug design. However, further experimental validation is crucial to advancing these ligands toward tangible antiviral therapeutics. This study contributes vital information to the computational drug discovery field, emphasizing interdisciplinary approaches for effective viral infection control.