Multi spectroscopic investigations with molecular docking and molecular dynamics simulation of the binding mechanism of molnupiravir to bovine serum albumin

Molnupiravir (MOL) is a recently developed oral antiviral drug. MOL has been clinically evaluated for its efficacy against COVID-19. In this work, we utilize UV-absorption spectroscopy, fluorescence spectroscopy, synchronous fluorescence, molecular docking and molecular dynamic (MD) simulation to study the interaction between MOL and bovine serum albumin (BSA). The fluorescence spectroscopic analysis indicated that MOL effectively quenched the intrinsic fluorescence of BSA. To elucidate the fluorescence quenching mechanism, the interaction of MOL with BSA was examined at five distinct temperatures (285 K, 290 K, 295 K, 303 K and 308 K). The quenching constants diminished as the temperature increased, suggesting a static quenching mechanism, as evidenced by the Stern-Volmer plots of F0/F against the molar concentrations of MOL. This was further confirmed by UV absorption spectroscopy. Thermodynamic analysis revealed a 1:1 stoichiometry for MOL binding to BSA, with a negative Gibbs free energy change (ΔG), confirming the spontaneous nature of binding. Competitive binding experiments using site-specific markers as well as molecular docking studies showed that MOL binds to site II. Synchronous fluorescence spectroscopy indicated that MOL was binding around tyrosine (Tyr) residues of the protein. These findings were further confirmed by the molecular docking and MD simulation studies. This research could provide valuable insights into the pharmacokinetics and pharmacodynamics of MOL, which could contribute to the development of more effective antiviral drugs.