Computational Studies of Cannabis Derivatives as Potential Inhibitors of SARS-CoV-2 M pro

Since the emergence of the coronavirus 2 (SARS-CoV-2), the approach taken to discover new drugs against this virus was to find reliable inhibitors of the main protease (M pro ) leading to minimize its proliferation and its complications observed in patients such as severe acute respiratory syndromes. In this regard, several works have been carried out based on this approach. In this investigation, combined computational studies were performed to examine the inhibitory performance of 12 cannabinoid-derived compounds and 38 terpene-derived compounds against SARS-CoV-2. At the beginning, a molecular docking study was done to predict the types of interactions and binding energies of each studied compound with respect to the active site of the main protease (M pro ). According to the docking results, seven compounds (THCV, CBN, Δ-9-THC, Δ-8-THC, CBC, THCA and CBCA) present high binding energies leading to strong interactions to their target protein. showed also more stable affinity energies than the reference drug, Narlaprevir. Then, the ADME-Tox (absorption, distribution, metabolism, excretion and toxicity) properties of these ligands were evaluated. As results, only one among the selected ligands showed that it could be selected as a potential anti-SARS-CoV-2 candidate. Finally, the binding stability of this compound in the active site of the main protease was confirmed through molecular dynamics simulation which was carried out on a time scale ranging from 0 to 100 ns. Graphic Abstract