Synthesis and In Silico Docking Study towards M-Pro of Novel Heterocyclic Compounds Derived from Pyrazolopyrimidinone as Putative SARS-CoV-2 Inhibitors

Abstract

In addition to vaccines, antiviral drugs are essential in order to suppress COVID-19. Although some inhibitor candidates have been determined to target the SARS-CoV-2 protein, there is still an urgent need to continue researching novel inhibitors of the SARS-CoV-2 main protease ‘Omicron P132H’, a protein that has recently been discovered. In the present study, in the search for therapeutic alternatives to treat COVID-19 and its recent variants, we conducted a structure-based virtual screening using docking studies for a new series of pyrazolo[3,4-d]pyrimidin-4(5H)-one derivatives 5–13, which were synthesized from the condensation reaction of pyrazolopyrimidinone-hydrazide (4) with a series of electrophiles. Some significant ADMET predictions–in addition to the docking results–were obtained based on the types of interactions formed and the binding energy values were compared to the reference anti- SARS-CoV-2 redocked drug nirmatrelvir.