Repurposing of SARS-CoV-2 compounds against Marburg Virus using MD simulation, mm/GBSA, PCA analysis, and free energy landscape.

The significant mortality rate associated with Marburg virus infection made it the greatest hazard among infectious diseases. Drug repurposing using methods has been crucial in identifying potential compounds that could prevent viral replication by targeting the virus's primary proteins. This study aimed at repurposing the drugs of SARS-CoV-2 for identifying potential candidates against the matrix protein VP40 of the Marburg virus. Virtual screening was performed where the control compound, Nilotinib, showed a binding score of -9.99 kcal/mol. Based on binding scores, hit compounds , , , , and were selected that had a lower binding score than the control. Subsequent molecular dynamics (MD) simulation revealed that compound consistently formed a hydrogen bond with the residue Gln. This was observed both in molecular docking and MD simulation poses, indicating a strong and significant interaction with the protein. had the most stable and consistent RMSD pattern exhibited in 100 ns simulation, while had the most identical RMSD plot compared to the control molecule. MM/PBSA analysis showed that the binding free energy (ΔG) of and was lower than the control, with -30.84 and -38.86 kcal/mol, respectively. It was observed by the PCA (principal component analysis) and FEL (free energy landscape) analysis that compounds and had lesser conformational variation. Overall, this study proposed and as potential binders of VP40 MARV that can cause its inhibition, however it inherently lacks experimental validation. Furthermore, the study proposes experiments as the next step to validate these computational findings, offering a practical approach to further explore these compounds' potential as antiviral agents.Communicated by Ramaswamy H. Sarma.