Imidazole-Based Alkaloids from Marine Sponges (Leucetta and Clathrina) as Potential Inhibitors Targeting SARS-CoV-2 Main Protease: An In Silico Approach

Imidazole-based compounds form a prominent class of heterocyclic compounds, displaying diverse applications, especially with regards to its biological and pharmacological activities. Molecular docking, simulations, and drug-likeness prediction were performed on 45 imidazole-based alkaloids from two species of marine sponges (Leucetta and Clathrina). The study seeks to identify possible inhibitors of the SARS-CoV-2 Main Protease in an effort to battle the prevailing pandemic which has been caused by the widespread infections of the SAR-CoV-2 virus in its varied mutated forms. Computational analysis with MOE 2015.10 program reveals that, among the imidazole-based alkaloids, Naamidines have a high affinity for the target protein (PDB ID:6W63), even interacting with the catalytic dyad, as compared to its non-covalent inhibitor X77. Among all the top-scoring ligands, Naamidine H produced the highest binding score of −8.87078 kcal/mol. MD simulation studies with NAMD confirms the stability of the interactions of Naamidines with the target protein. MM-GBSA calculations were performed on the top binding ligands which further confirms the binding affinity of the top-scoring ligands. Computational and pharmacological investigations in this study proposes Naamidines, as effective inhibitors of Mpro. Naamidine I, Naamidine E, and Pyronaamidine could be potential anti-viral candidates against SAR-CoV-2.