Detection of the antiviral activity of epicatechin isolated from Salacia crassifolia (Celastraceae) against Mayaro virus based on protein C homology modelling and virtual screening

Abstract

Mayaro fever, caused by Mayaro virus (MAYV) is a sub-lethal disease with symptoms that are easily confused with those of dengue fever, except for polyarthralgia, which may culminate in physical incapacitation. Recently, outbreaks of MAYV have been documented in metropolitan areas, and to date, there is no therapy or vaccine available. Moreover, there is no information regarding the three-dimensional structure of the viral proteins of MAYV, which is important in the search for antivirals. In this work, we constructed a three-dimensional model of protein C of MAYV by homology modelling, and this was employed in a manner similar to that of receptors in virtual screening studies to evaluate 590 molecules as prospective antiviral agents. In vitro bioassays were utilized to confirm the potential antiviral activity of the flavonoid epicatechin isolated from Salacia crassifolia (Celastraceae). The virtual screening showed that six flavonoids were promising ligands for protein C. The bioassays showed potent antiviral action of epicatechin, which protected the cells from almost all of the effects of viral infection. An effective concentration (EC) of 0.247 μmol/mL was observed with a selectivity index (SI) of 7. The cytotoxicity assay showed that epicatechin has low toxicity, with a 50% cytotoxic concentration (CC) greater than 1.723 µmol/mL. Epicatechin was found to be twice as potent as the reference antiviral ribavirin. Furthermore, a replication kinetics assay showed a strong inhibitory effect of epicatechin on MAYV growth, with a reduction of at least four logs in virus production. Our results indicate that epicatechin is a promising candidate for further testing as an antiviral agent against Mayaro virus and other alphaviruses.

Mayaro: an emerging viral threat?

“…These affect early and late stages and morphogenesis, in particular showing the potential application of this new class of antiviral drugs with low cytotoxicity and good bioavailability 75 . In addition, a recent study published by Ferreira et al 76 showed a strong inhibitory effect of epicatechin on MAYV growth, indicating that this is a promising candidate against MAYV.…”

<strong>Antiviral phytochemicals identified in <em>Rhododendron arboreum</em> petals exhibited strong binding to SARS-CoV-2 M^Pro and Human ACE2 receptor</strong>

“…Catechins are reported activities against influenza (Song et al, 2005), hepatitis B virus (Li et al, 2001) and docking against ACE2 receptor (Jena et al, 2019). Epicatechin has been reported against Mayaro virus (Ferreira et al, 2018). The antiviral activities of phytochemicals from R. arboreum petal extracts such as Caffeic acid, Kaempferol, Quercetin, Shikimic acid, 4-Coumaric acid and other are tabulated (Table S5).…”

Schinus terebenthifolius Raddi extracts: From sunscreen activity toward protection of the placenta to Zika virus infection, new uses for a well-known medicinal plant

“…Antimicrobial and antiviral (showed inhibition against Herpes simplex virus type 1 (HSV-1) (Musarra-Pizzo et al, 2019) Anti-oxidant, antitumor, antibacterial, antifungal, antidiabetic, anti-inflammatory, antiproliferative and antitumor (Cosarcã et al, 2019) Antioxidant, UV protective, anti-allergenic, anti-inflammatory, anti-microbial, anti-viral and anti-cancer (Bae et al, 2020) Antiviral (showed inhibition against pandemic influenza A (H1N1) (You et al, 2018) Epicatechin Antiviral (showed inhibitory effect against Mayaro (MAYV) virus and other alphavirus viruses (Ferreira et al, 2018) Antinociceptive and anti-inflammatory (Dias et al, 2018) Antibacterial (Ezhil and Lakshmi, 2017) Antidiabetic (Ibrahim et al, 2018) Anti-infective (Song, 2017) Anti-oxidant, antimicrobial, anti-inflammatory, antitumor, antidiabetic, anticancer and cardioprotective (Prakash et al, 2019) Antioxidant and anticollagenase (showed a high inhibitory power against the collagenase enzyme, responsible for the degradation of matrix collagen and the photo-aging process. (Geeta et al, 2019) UV protection (Prasanth et al, 2020)…”