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.
Highlights
IntroductionCoronavirus disease 2019 (COVID-19) is caused by a novel positive-sense singlestranded RNA virus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)
Coronavirus disease 2019 (COVID-19) is caused by a novel positive-sense singlestranded RNA virus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).This virus has been classified under family Coronaviridae, subfamily Coronaviridae and order nidovirales [1]
A total of 50 natural products reported in E. angustifolia were docked in the binding pocket of viral main protease (Mpro ) using the Glide XP protocol, yields ligands with binding affinities in the range of -12.93 to 0.0897 kcal/mol, at least docking root mean square deviation (RMSD) values as shown in Echinacoside (ECH), a natural phenylethanoid glycoside, has been investigated for numerous pharmacologically benefits possessing high antiviral activities [44], and limited immune activation properties [45]
Summary
Coronavirus disease 2019 (COVID-19) is caused by a novel positive-sense singlestranded RNA virus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This virus has been classified under family Coronaviridae, subfamily Coronaviridae and order nidovirales [1]. The viral protein nsp, termed as 3C-like proteinase (3CLpro ) or main protease (Mpro ), is a key for processing of polyprotein into the functional proteins [3]. It has been recognized as an important anti-SARS-CoV-2 target due to its essential role in viral replication. Targeting and inhibiting the activity of Mpro might block or impair viral replication [4]
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