Reynoutria Rhizomes as a Natural Source of SARS-CoV-2 Mpro Inhibitors–Molecular Docking and In Vitro Study

Abstract

More than a year has passed since the world began to fight the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the Coronavirus disease 2019 (COVID-19) pandemic, and still it spreads around the world, mutating at the same time. One of the sources of compounds with potential antiviral activity is Traditional Chinese Medicinal (TCM) plants used in China in the supportive treatment of COVID-19. Reynoutria japonica is important part of the Shu Feng Jie Du Granule/Capsule-TCM herbal formula, recommended by China Food and Drug Administration (CFDA) for treatment of patients with H1N1- and H5N9-induced acute lung injury and is also used in China to treat COVID-19, mainly combined with other remedies. In our study, 25 compounds from rhizomes of R. japonica and Reynoutria sachalinensis (related species), were docked into the binding site of SARS-CoV-2 main protease. Next, 11 of them (vanicoside A, vanicoside B, resveratrol, piceid, emodin, epicatechin, epicatechin gallate, epigallocatechin gallate, procyanidin B2, procyanidin C1, procyanidin B2 3,3’-di-O-gallate) as well as extracts and fractions from rhizomes of R. japonica and R. sachalinensis were tested in vitro using a fluorescent peptide substrate. Among the tested phytochemicals the best results were achieved for vanicoside A and vanicoside B with moderate inhibition of SARS-CoV-2 Mpro, IC50 = 23.10 µM and 43.59 µM, respectively. The butanol fractions of plants showed the strongest inhibition of SARS-CoV-2 Mpro (IC50 = 4.031 µg/mL for R. sachalinensis and IC50 = 7.877 µg/mL for R. japonica). As the main constituents of butanol fractions, besides the phenylpropanoid disaccharide esters (e.g., vanicosides), are highly polymerized procyanidins, we suppose that they could be responsible for their strong inhibitory properties. As inhibition of SARS-CoV-2 main protease could prevent the replication of the virus our research provides data that may explain the beneficial effects of R. japonica on COVID-19 and identify the most active compounds worthy of more extensive research.

New Approaches on Japanese Knotweed (Fallopia japonica) Bioactive Compounds and Their Potential of Pharmacological and Beekeeping Activities: Challenges and Future Directions

“…The report made by Nawrot-Hadzik et al ( 2021) showed significant effects of the butanol fractions from R. japonica and R. sachalinensis (especially vanicosides) on the inhibition of SARS-CoV-2 Mpro cells (7.877 g/mL, 4.031 g/mL, respectively at IC 50 ). However, these constituents may act in synergy with other compounds such as polymerized procyanidins that can also exhibit a strong inhibitory activity on the antiviral pathway, as suggested by previous authors [112].…”

“…Recently, it became the spotlight of numerous studies, since its chemical composition has revealed promising therapeutic effects. Alcoholic, hydroalcoholic and water extracts from roots, rhizomes, and aerial parts (stems, leaves and flowers) have antibacterial activity [64,66,[93][94][95], antioxidant effects [44,58,66,[96][97][98][99][100][101][102][103][104][105], anticancer, antiproliferative and apoptotic properties [106][107][108], anti-inflammatory and antiviral activity [11,69,[109][110][111][112] and many other bioactive properties.…”

Promising Role of Emodin as Therapeutics to Against Viral Infections

“…The main protease (Mpro, also called 3CLpro) is the nonstructural proteins of the virus, and inhibition of this enzyme could prevent the replication of the virus. Found that emodin revealed over 50% inhibition of SARS-CoV-2 Mpro, suggesting the beneficial effects of emodin on COVID-19 Nawrot-Hadzik et al (2021) . In order to improve the activity of emodin against human coronavirus NL63 (HCoV-NL63) and also to generate a set of initial SAR guidelines, Monika et al prepared emodin derivatives and found that halogenation of emodin can improve the antiviral activity of which.…”

“…Similarly, herbal medicines and their active ingredients have been shown to have significant antiviral effects ( Shao et al, 2021 ). There are some evidences (including in silico study and cell experiments) indicating that emodin might be effective therapy factor against SARS-CoV and COVID-19 ( Ho et al, 2007 ; Schwarz et al, 2011 ; Batista et al, 2019 ; Basu et al, 2020 ; Caruso et al, 2020 ; Boozari and Hosseinzadeh, 2021 ; Nawrot-Hadzik et al, 2021 ; Rolta et al, 2021 ), suggesting that it may be an effective new antiviral agent. Through collection and collation of related literature, we found that emodin also has good antiviral effects on other viruses, so the aim of this review is to collect and present the current experimental evidence for the antivirus efficacy and underlying mechanisms of emodin, with a view to informing the development of new antiviral drugs.…”

Jeopardy of COVID-19: Rechecking the Perks of Phytotherapeutic Interventions

“…Additionally, the ability of the theaflavin, a component of black tea, in inhibiting the RNA dependent RNA polymerase (RdRP) active site is well documented in many recent works on COVID-19 research [82]. Bioactive compounds like vanicoside B, resveratrol, epicatechin, emodin, piceid, epicatechin from various medicinal plants including Reynoutria japonica and Reynoutria sachalinensis was found effective against the main protease (Mpro) [83]. Nimbin, gedunin, and ginsenosides, important constituents of Panax ginseng, Zingiber officinale, Ocimum basilicum are potential inhibitors of the main protease required for viral replication process of coronaviruses [84].…”