new potential inhibitors of coronaviral main protease (cov-mpro): strychnine bush, pineapple, and ginger could be natural enemies of covid-19

the coronavirus disease 2019 (covid-19) has certainly become a global pandemic. the presence of the deadly coronavirus pandemic in the world called the necessity to well identify and characterize new drug candidates for addressing the health issues and problems caused by the severe acute respiratory syndrome coronavirus 2 (sars-cov-2). this current research aims to find candidate anti-covid-19 compounds from the natural herbal sources, mainly, strychnine bush (strychnos lucida), pineapple (ananas comosus), and ginger (zingiber officinale) to act as efficient inhibitors and blockers of the coronaviral-2 main protease (mpro) receptor based on computational molecular docking modeling evaluation (i.e., simulative computational testing). the docking procedures were successfully performed on mpro using a crystal structure of mpro in complex with an inhibitor n3, it was downloaded from the protein data bank (pdb) database with the code of 6lu7, and it was prepared for small molecule docking. the docking protocol was carried out using mainly n3 comparison utilizing four known potential anti-covid-19 drugs, favipiravir, gs-441524 (the active metabolite of remdesivir), remdesivir, and hydroxychloroquine, as positive controls. the docking results frankly show that the compounds ananas 26, zingiberenol, and zingiberol have lower binding energies and, therefore, higher inhibitory binding affinities compared to the native ligand n3, the other tested ingredients, and the active references (favipiravir, gs-441524, remdesivir, and hydroxychloroquine). ananas 26 compound has the strongest hydrogen bonds with the coronaviral-2 mpro active amino acid residues, namely: his163, asn142, asp187, tyr54, and his41. specifically, this makes ananas 26 much more stable in the binding pockets and cavities of the mpro enzyme and, therefore, more effective in inhibiting the enzyme performance/activity than the other candidate compounds and positive controls. potential candidate compounds as covid-19 mpro inhibitors, ananas 26 from pineapple and zingiberenol as well as zingiberol from ginger, can further undergo potential inhibitor assays and be subjected to in vitro and in vivo tests for evaluating and proving their biological activities against sars-cov-2 and covid-19.