Natural antiretroviral compounds as the inhibitors of the SARS-CoV-2 M protein

The intricate structure of the membrane protein in SARS-CoV-2 presents a challenge for experimental analysis. This protein plays a crucial role in both the viral infection cycle and virus development. Consequently, it represents a compelling target for therapeutic interventions and vaccine development. Given our limited understanding of its experimental structure, we employed homology modeling to generate a structural approximation of the SARS-CoV-2 membrane protein. Subsequently, we conducted a 100 ns molecular dynamics simulation of the developed model. Ten poses, each at 10 ns dynamics, of the model structure, were extracted from the dynamical pathway which were utilized for the molecular docking of the natural ligands chosen from the ZINC12 database. Further, molecular dynamics simulation of 100 ns of the top two protein-ligand complexes from clusters having better docking scores, incorporating a membrane environment, have been carried out. Through this simulation, we identified active site residues and analyzed the binding positions of potential drug candidates. Our analysis focused on identifying drugs that exhibited better free energy of binding and remained stable for the longest duration during the molecular dynamics simulations. The results provide insights into potential candidates SA_0124 and BMC_0005 for targeting the modeled SARS-CoV-2 membrane protein, offering valuable contributions to ongoing drug discovery efforts.