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.

Mechanisms and potential therapeutic targets of hyperinflammatory responses in SARS-CoV2 Ifeoma felIcIa chukwuma 1 , VIctor onukwube apeh 1 , okwesIlIeze frederIck c. nwodo 2

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The geometrical increase in diabetes mellitus (DM) and the undesirable side effects of synthetic drugs have intensified efforts to search for an effective and safe anti-diabetic therapy. This study aimed to identify the antioxidant and anti-diabetic agents in the ethanol extract of Leptadenia hastata (EELH). The phytochemicals, antioxidant vitamins, and minerals present in EELH were determined using standard procedures to achieve this aim. Gas chromatography coupled with mass spectroscopy and flame ionization detector (GC-MS/GC-FID) was employed to identify bioactive compounds. An e-pharmacophore model was generated from the extra precision, and energy-minimized docked position of standard inhibitor, acarbose onto human pancreatic amylase (HPA, PDB-6OCN). It was used to screen the GC-MS/GC-FID library of compounds. The top-scoring compounds were subjected to glide XP-docking and prime MM-GBSA calculation with the Schrodinger suite-v12.4. The Adsorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) prediction of the best-fit compounds was made using SwissADME and PROTOX-II webservers. Further validation of the docking results was performed with the in vitro analysis of the α-amylase and α-glucosidase inhibitory activities. EELH contains appreciable amounts of antioxidant and anti-diabetic phytoconstituents. The top-4 scoring compounds (rutin, epicatechin, kaempferol, and naringenin) from the EELH phytochemical library interacted with amino acid residues within and around the HPA active site. The ADMET prediction shows that epicatechin, kaempferol, and naringenin had favorable drug-likeness, pharmacokinetic properties, and a good safety profile. EELH demonstrated good inhibitory actions against α-amylase and α-glucosidase with 1C50 values of 14.14 and 4.22 µg/mL, respectively. Thus, L hastata phytoconstituents are promising novel candidates for developing an anti-diabetic drug.

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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 identify the bioactive compounds of the plants that are responsible for this activity, for the purpose of designing drugs against SARS-CoV-2. In this study, we employed in silico techniques comprising of molecular docking, binding free energy calculations, pharmacophore modelling as well as druglikeness, pharmacokinetics and toxicity 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 highest; with docking scores ranging from -7.84 to -7.15 kcal/mol compared with -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. These compounds also possess acceptable druglike properties and safety profile. Hence, they could be considered for experimental studies and further development into drugs against SARS-CoV-2.

Epidermal Growth Factor Receptor (EGFR) tyrosine kinase is a cell surface receptor whose overexpression has been associated with different types of cancers including brain cancer (glioblastoma multiforme). The ability of the extract of Scutellaria baicalensis to inhibit the proliferation of malignant glioma cells have been reported. Thus, in this study we report the identification of 307 bioactive constituents responsible for the anti-glioblastoma multiforme effect from S. baicalensis using in silico studies such as molecular docking, binding free energy calculations, pharmacophore modelling, induced-fit docking, gene enrichment analysis, molecular dynamic simulations and AD-MET predictions. A total of 307 chemical constituents of S. baicalensis were screened and the top 10 scoring compounds indicated different binding affinities ranging from -9.010 to -6.427 kcal/mol towards the EGFR tyrosine kinase; Ganhuangenin, 5,7,2',5'-tetrahydroxyflavone, (2R)-2-(2,6-dihydroxyphenyl)-3,4-dihydro-2H-chromene-5,7-diol, and tenaxin I possess higher binding affinities (-9.010 to -8.649 kcal/mol) compared to the standard ligand, erlotinib having -8.539 kcal/mol. The

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