Structure-Based Identification of Natural Products as SARS-CoV-2 Mpro Antagonist from Echinacea angustifolia Using Computational Approaches

Abstract

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 (Mpro) 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 Mpro. 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 Mpro catalytic pocket via substantial intermolecular contacts formation against co-crystallized ligand (< -4 kcal/mol). Furthermore, the docked poses of SARS-CoV-2 Mpro 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 Mpro antagonist with higher affinity and drug-likeness.

COVID-19 in 2021

“…Structural biology has also supported drug discovery by identifying natural products acting as SARS-CoV-2 Mpro inhibitors [ 17 ]. Based on computational approaches, natural products from the coneflower Echinacea augustifolia were discovered as potent inhibitors of Mpro and could be attractive drug candidates against SARS-CoV-2.…”

Virtual Combinatorial Library Screening of Quinadoline B Derivatives against SARS-CoV-2 RNA-Dependent RNA Polymerase

“…The continued rise in COVID-19 cases worldwide despite the availability of vaccines sustains the demand to discover treatment and prophylactic regimens, particularly through natural products' repurposing and design [1][2][3]. Computational strategies play a crucial role in accelerating the discovery of effective anti-SARS-CoV-2 agents [4][5][6][7][8], as in silico experiments are vital in the screening of biologically active compounds, offering a rapid, low-cost, and effective adjunct to in vitro and in vivo experiments. Such methods can facilitate the iteration of known potential compounds to further enhance their biological and pharmacokinetic activities, capable of constructing virtually all possible permutational derivatives from a single parent compound [9].…”

Computational and In Vitro Experimental Investigations Reveal Anti-Viral Activity of Licorice and Glycyrrhizin against Severe Acute Respiratory Syndrome Coronavirus 2

“…The new Coronavirus Disease 2019 (COVID-19) has become a heath nuisance all over the world due to a lack of specific and potent medication [1][2][3]. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19 pandemic, can transmit from one infected person to another through aerosols [4].…”