Astaxanthin-Based Drug Design: A Virtual Screening Study for COVID-19 Main Protease Inhibition

The main purpose of this study was to assess the capability of Astaxanthin, a carotene compound, as a potential organic inhibitor of coronavirus main protease by computational techniques and approaches. To design new inhibitors based on Astaxanthin structure, compare them with the co-crystal inhibitor N3, as a potent inhibitor of the COVID-19 main protease, and determine if the new structures have similar or better binding affinity to the COVID-19 main protease, different virtual screening methods such as Molecular Docking, Structure-Based Drug Design, Ligand-Based Drug Design, Molecular Dynamic Simulation, and Synthesis Accessibility Prediction were used. The hit compounds were selected based on their highest binding energy ranging from − 8.3 to -9.2, Lipinski's (Pfizer's) rule of five, and the Synthesis Accessibility scores to indicate the easy to synthesis compounds. The stability of ligands with the proteins at their active sites was further confirmed through molecular dynamics. Our results suggested that the selected compounds had favorable interactions at the binding pocket of the coronavirus main protease, and exhibited better binding affinities and simpler structures compared to N3. The suggested compounds could be used as lead compounds for further drug development and optimization. However, more experimental and clinical validation is required to approve their efficacy and safety.