ABSTRACT
The coronavirus disease 2019 (COVID-19) has become a serious problem for public health since it was identified in the province of Wuhan (China) and spread around the world producing high mortality rates and economic losses. Nowadays, WHO recognizes traditional, complementary, and alternative medicine for treating COVID-19 symptoms. Therefore, we investigated the antiviral potential of the hydroalcoholic extract of Uncaria tomentosa stem bark from Peru against SARS-CoV-2 in vitro. The antiviral activity of U. tomentosa against SARS-CoV-2 in vitro was assessed in Vero E6 cells using cytopathic effect (CPE) and plaque reduction assay. After 48h of treatment, U. tomentosa showed an inhibition of 92.7 % of SARS-CoV-2 at 25.0 g/mL (p<0.0001) by plaque reduction assay on Vero E6 cells. In addition, U. tomentosa, induced a reduction of 98.6 % (p=0.02) and 92.7 % (p=0.03) in the CPE caused by SARS-CoV-2 on Vero E6 cells at 25 g/mL and 12.5 g/mL, respectively. The EC50 calculated for U. tomentosa extract by plaque reduction assay was 6.6 g/mL (4.89 - 8.85 g/mL) for a selectivity index of 4.1. The EC50 calculated for U. tomentosa extract by TCID50 assay was 2.57 g/mL (1.05 - 3.75 g/mL) for a selectivity index of 10.54. These results showed thatU. tomentosa known as Cat's claw has antiviral effect against SARS-CoV-2 observed as a reduction in the viral titer and CPE after 48h of treatment on Vero E6 cells. Therefore, we hypothesized that U. tomentosa stem bark, could be promissory to the development of new therapeutic strategies against SARS-CoV-2.
Subject(s)
COVID-19ABSTRACT
COVID-19 is a novel severe acute respiratory syndrome coronavirus. Presently, there is no effective treatment for COVID-19. As part of the worldwide efforts to find efficient therapies and preventions, it has been reported the crystalline structure of the SARS-CoV-2 main protease Mpro (also called 3CLpro) bound to a synthetic inhibitor which represents a major druggable target. The druggability of Mpro could be used for discovering drugs to treat coronavirus disease 2019. It was carried out a multi-level computational study to evaluate the potential anti-viral properties of the components of the medicinal herb Uncaria tomentosa (Cat´s claw) focusing on the inhibition of Mpro. The in-silico approach starts with protein-ligand docking of 26 Cat’s claw key components followed by ligand pathway calculations, molecular dynamics simulations and MM-GBSA calculation of the free energy of binding for the best docked candidates. The structural bioinformatics approaches led to the identification of three bioactive compounds of Uncaria tomentosa (Speciophylline, Cadambine and Proanthocyanidin B2) with potential therapeutic effects by strong interaction with 3CLpro. Additionally, in silico drug-likeness indices for these components were calculated and show good predicted therapeutic profiles of these phytochemicals. Our findings suggest the potential effectiveness of Cat's claw as complementary and/or alternative medicine for COVID-19 treatment.