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. 2020 Dec;34(12):3411-3419.
doi: 10.1002/ptr.6802. Epub 2020 Aug 4.

Evaluation of medicinal herbs as a potential therapeutic option against SARS-CoV-2 targeting its main protease

Saurabh Upadhyay  1 , Praveen K Tripathi  1 , Manju Singh  2 , Siva Raghavendhar  1 , Mohit Bhardwaj  1 , Ashok K Patel  1
Affiliations

Evaluation of medicinal herbs as a potential therapeutic option against SARS-CoV-2 targeting its main protease

Saurabh Upadhyay et al. Phytother Res. 2020 Dec.

Abstract

The COVID-19 disease caused by the SARS-CoV-2 has emerged as a worldwide pandemic and caused huge damage to the lives and economy of more than hundred countries. As on May 10, 2020, more than 4,153,300 people stand infected from the virus due to an unprecedented rate of transmission and 282,700 have lost their lives because of the disease. In this context, medicinal plants may provide a way to treat the disease by targeting specific essential proteins of the virus. We screened about 51 medicinal plants and found that Tea (Camellia sinensis) and Haritaki (Terminalia chebula) has potential against SARS-COV-2 3CLpro , with an IC50 for Green Tea as 8.9 ± 0.5 μg/ml and Haritaki 8.8 ± 0.5 μg/ml. The in-silico studies suggested that Tea component Thearubigins binds to the cysteine 145 of protease active site and could be a pharmacoactive molecule. We predict that the inhibition in protease activity may be able to halt the SARS-CoV-2 replication cycle and therefore, we propose Green Tea, Black Tea, and Haritaki plant extracts as potential therapeutic candidates for SARS-CoV-2 infection. Further investigation on role of bioactive constituents of extracts is needed to establish the molecular basis of inhibition and towards expedited drug discovery.

Keywords: 3CLpro; Haritaki; SARS-CoV-2; medicinal plants; tea.

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Conflict of interest statement

Authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Cloning and purification of 3CLpro protein. (A) 1% agarose gel showing the bands of the double digested plasmid with vector 5.4 kb and insert around 918 bases (L2), the cloned plasmid showing band at 6.4 kb (L3). (B) SDS‐PAGE on 12% acrylamide gel, depicting homogenous protein at ~34 kDa (C) The western blot of purified 3CLpro using anti‐His antibody with mol wt ~34 kDa (L2) [Colour figure can be viewed at wileyonlinelibrary.com]
FIGURE 2
FIGURE 2
Enzyme kinetic studies of 3CLpro. (A) Evaluation of kinetic parameters in Michaelis–Menten fit. The varying concentration of the casein substrate (x‐axis) plotted against the velocity (y‐axis). (B) Inverse substrate versus inverse velocity plot (Lineweaver–Burk plot) depicting the casein substrate cleavage by the action of 3CLpro. All the experiments were performed in triplicates [Colour figure can be viewed at wileyonlinelibrary.com]
FIGURE 3
FIGURE 3
Determination of inhibitory concentration of plant extracts. The inhibition of percentage enzyme activity in the presence of varying concentrations (0–450 μg/ml) of plant extracts are shown. The value at which the 50% enzyme activity‐reduction observed is taken as IC50 of individual extracts. All the experiments were performed in triplicates. Error bars represent SEM [Colour figure can be viewed at wileyonlinelibrary.com]
FIGURE 4
FIGURE 4
Estimation of tertiary structure perturbation in the presence of plant extracts. (A) Titration of 3CLpro with varying concentrations of Green Tea (Camellia sinensis). (B) Titration of 3CLpro with varying concentrations of Haritaki (Terminalia chebula) [Colour figure can be viewed at wileyonlinelibrary.com]
FIGURE 5
FIGURE 5
The comparison of inhibitory potential between Green Tea, Black Tea, and Haritaki towards 3CLpro activity inhibition. The graph represents the activity inhibition by Green Tea, Black Tea, and Haritaki. All the experiments were performed in triplicates and error bars represent SEM [Colour figure can be viewed at wileyonlinelibrary.com]
FIGURE 6
FIGURE 6
Active site details and binding of thearubigin. (A) Structure of native 6LU7 (green) and bounded (yellow), the active site space determined by metapocket2.0 (MPT in magenta), and the active site residues His41 and Cys145. (B) 2‐D interaction diagram of thearubigin with the residues of the active site. The interaction profile of quercetin‐3‐O‐rutinoside (C), and hesperidin (D) [Colour figure can be viewed at wileyonlinelibrary.com]
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