Synthesis, X-Ray Crystal Structure, and Identification of Potential Drug Candidate against COVID-19 Main Protease through Structure-Guided Modeling and Simulation Approach

5-Acetyl-4-(4-methoxyphenyl)-6-methyl-2-thioxo-1,2-dihydropyridine-3-carbonitrile has been successfully prepared by the condensation between the acetylacetone and 2-cyano-3-(4'-methoxyphenyl)thio acrylamide and used to search for a potential drug that could be used to treat COVID-19. The structure was characterized and confirmed by X-ray diffraction analysis, and the crystal packing stability was also performed by the Hirshfeld surface analysis. The chemical reactivity and other properties of the title compound were determined using the density functional theory (DFT) computation and the NBO analysis. Also, the molecular electrostatic potential (MEP) surface was investigated. The CN group was the most nucleophilic site in the entire molecule based on the results. The title compound’s in-silico molecular docking revealed a strong binding potential. Eventually, molecular dynamic (MD) simulation studies are conducted to examine the stability of the molecule inside the receptor cavity. The findings of the in-silico analysis manifested affirmative evidence for the title molecule with good binding, as a potent inhibitor for the main protease of SARS-Cov-2. Hence, it holds the striking potential to serve as a prospective lead compound for designing efficacious drugs against COVID-19.