Acridone Alkaloids: In-Silico Investigation Against SARS-CoV-2 Main Protease

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that causes COVID-19 disease is still a major public health concern around the world. The main protease encoded by SARS-CoV-2 is a promising target for COVID-19 therapeutic development since it plays a crucial role in the virus’s life cycle. Repurposing known bioactive molecules is an effective strategy to fast-track the delivery of hits and leads in drug discovery. In this regard, this study assesses in-silico, 17 acridone-based alkaloids for their activity against SARS-CoV-2 main protease. The quantum chemical computations imply that the acridone alkaloids will interact better in the active sites of the enzymes due to their low energy gap. They also have good oral bioavailability as rationalized by “no rule of five violation" and favorable pharmacokinetics parameters. From the docking results, many of the alkaloids displayed a higher binding affinity than nirmatrelvir, an authorised protease inhibitor. Compound 3 (5-hydroxynoracronycine alcohol), with the better binding affinities (6W63, − 7.094 kcal/mol; 5R82, − 5.839 kcal/mol) and unique structural features is a viable candidate that could be investigated further for development of a novel target specific chemotherapeutic agent to stop SARS-CoV-2 invasion.