discovery of SARS-CoV-2 main protease inhibitors from the carboline and quinoline database.

SARS-CoV-2 caused more than 3.8 million deaths according to the WHO. In this urgent circumstance, we aimed at screening out potential inhibitors targeting the main protease of SARS-CoV-2. An in-house carboline and quinoline database including carboline, quinoline and their derivatives was established. A virtual screening in carboline and quinoline database, 50 ns molecular dynamics simulations and molecular mechanics Poisson-Boltzmann surface area calculations were carried out. The top 12 molecules were screened out preliminarily. The molecular mechanics Poisson-Boltzmann surface area ranking showed that p59_7m, p12_7e, p59_7k stood out with the lowest binding energies of -24.20, -17.98, -17.67 kcal/mol, respectively. The study provides powerful results that indicate the selected molecules are valuable for further evaluation as SARS-CoV-2 main protease inhibitors.