Structure-Based Identification of Natural Products as SARS-CoV-2 M(pro) Antagonist from Echinacea angustifolia Using Computational Approaches

Bharadwaj, Shiv; El-Kafrawy, Sherif Aly; Alandijany, Thamir A.; Bajrai, Leena Hussein; Shah, Altaf Ahmad; Dubey, Amit; Sahoo, Amaresh Kumar; Yadava, Umesh; Kamal, Mohammad Amjad; Azhar, Esam Ibraheem; Kang, Sang Gu; Dwivedi, Vivek Dhar

Coronavirus disease-19 (COVID-19) pandemic, caused by the novel SARS-CoV-2 virus, continues to be a global threat. The number of cases and deaths will remain escalating due to the lack of effective therapeutic agents. Several studies have established the importance of the viral main protease (M(pro)) in the replication of SARS-CoV-2 which makes it an attractive target for antiviral drug development, including pharmaceutical repurposing and other medicinal chemistry approaches. Identification of natural products with considerable inhibitory potential against SARS-CoV-2 could be beneficial as a rapid and potent alternative with drug-likeness by comparison to de novo antiviral drug discovery approaches. Thereof, we carried out the structure-based screening of natural products from Echinacea-angustifolia, commonly used to prevent cold and other microbial respiratory infections, targeting SARS-CoV-2 M(pro). Four natural products namely, Echinacoside, Quercetagetin 7-glucoside, Levan N, Inulin from chicory, and 1,3-Dicaffeoylquinic acid, revealed significant docking energy (>−10 kcal/mol) in the SARS-CoV-2 M(pro) catalytic pocket via substantial intermolecular contacts formation against co-crystallized ligand (<−4 kcal/mol). Furthermore, the docked poses of SARS-CoV-2 M(pro) with selected natural products showed conformational stability through molecular dynamics. Exploring the end-point net binding energy exhibited substantial contribution of Coulomb and van der Waals interactions to the stability of respective docked conformations. These results advocated the natural products from Echinacea angustifolia for further experimental studies with an elevated probability to discover the potent SARS-CoV-2 M(pro) antagonist with higher affinity and drug-likeness.