AUTHOR=Johnson Titilayo Omolara , Adegboyega Abayomi Emmanuel , Ojo Oluwafemi Adeleke , Yusuf Amina Jega , Iwaloye Opeyemi , Ugwah-Oguejiofor Chinenye Jane , Asomadu Rita Onyekachukwu , Chukwuma Ifeoma Felicia , Ejembi Stephen Adakole , Ugwuja Emmanuel Ike , Alotaibi Saqer S. , Albogami Sarah M. , Batiha Gaber El-Saber , Rajab Bodour S. , Conte-Junior Carlos Adam TITLE=A Computational Approach to Elucidate the Interactions of Chemicals From Artemisia annua Targeted Toward SARS-CoV-2 Main Protease Inhibition for COVID-19 Treatment JOURNAL=Frontiers in Medicine VOLUME=9 YEAR=2022 URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.907583 DOI=10.3389/fmed.2022.907583 ISSN=2296-858X ABSTRACT=

The inhibitory potential of Artemisia annua, a well-known antimalarial herb, against several viruses, including the coronavirus, is increasingly gaining recognition. The plant extract has shown significant activity against both the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and the novel SARS-CoV-2 that is currently ravaging the world. It is therefore necessary to evaluate individual chemicals of the plant for inhibitory potential against SARS-CoV-2 for the purpose of designing drugs for the treatment of COVID-19. In this study, we employed computational techniques comprising molecular docking, binding free energy calculations, pharmacophore modeling, induced-fit docking, molecular dynamics simulation, and ADMET predictions to identify potential inhibitors of the SARS-CoV-2 main protease (Mpro) from 168 bioactive compounds of Artemisia annua. Rhamnocitrin, isokaempferide, kaempferol, quercimeritrin, apigenin, penduletin, isoquercitrin, astragalin, luteolin-7-glucoside, and isorhamnetin were ranked the highest, with docking scores ranging from −7.84 to −7.15 kcal/mol compared with the −6.59 kcal/mol demonstrated by the standard ligand. Rhamnocitrin, Isokaempferide, and kaempferol, like the standard ligand, interacted with important active site amino acid residues like HIS 41, CYS 145, ASN 142, and GLU 166, among others. Rhamnocitrin demonstrated good stability in the active site of the protein as there were no significant conformational changes during the simulation process. These compounds also possess acceptable druglike properties and a good safety profile. Hence, they could be considered for experimental studies and further development of drugs against COVID-19.