原花青素对马亚罗病毒的抗病毒活性。

Virucidal activity of proanthocyanidin against Mayaro virus.

机构信息

Department of Chemistry, Biotechnology and Bioprocess Engineering, Federal University of São João del-Rei, Campus Alto Paraopeba, Ouro Branco, Minas Gerais, Brazil; Federal University of São João del-Rei, Campus Centro Oeste Dona Lindu, Divinópolis, Minas Gerais, Brazil.

Department of Chemistry, Biotechnology and Bioprocess Engineering, Federal University of São João del-Rei, Campus Alto Paraopeba, Ouro Branco, Minas Gerais, Brazil.

出版信息

Antiviral Res. 2019 Aug;168:76-81. doi: 10.1016/j.antiviral.2019.05.008. Epub 2019 May 21.

DOI:10.1016/j.antiviral.2019.05.008

PMID:31125633

Abstract

Mayaro virus (MAYV) is a sublethal arbovirus transmitted by mosquitoes with possible installation of an urban cycle in the Americas. Its infection causes disabling arthralgia, and still, there is no vaccine or treatment to it. We recently investigated nearly 600 compounds by molecular docking and identified epicatechin as a potent antiviral against MAYV. The root extract of Maytenus imbricata showed anti-MAYV activity and two isolated compounds from this plant were also evaluated in vitro. Proanthocyanidin (PAC), a dimer containing epicatechin, showed an effective concentration for 50% of the cells infected by MAYV (EC) of 37.9 ± 2.4 μM and a selectivity index (SI) above 40. PAC showed significant virucidal activity, inhibiting 100% of the virus proliferation (7 log units), and caused moderate effect during adsorption and virus internalization stage. However, PAC was unable to block the infection when only the cells were pretreated. It was observed a reduction in virus yields when adding PAC at different moments after infection. The set of results indicates that PAC binds to viral and non-cellular elements and may inactivate the MAYV. The inactivation occurs before infection or when the virus reaches the extracellular environment from the 2nd cycle of infection that could block its progression cell-to-cell or to tissues not yet infected.

摘要

玛雅罗病毒（MAYV）是一种通过蚊子传播的亚致死性虫媒病毒，在美洲可能存在城市循环。其感染会导致关节疼痛，目前仍没有针对它的疫苗或治疗方法。我们最近通过分子对接研究了近 600 种化合物，发现表儿茶素是一种对抗 MAYV 的有效抗病毒药物。马缨丹的根提取物具有抗 MAYV 活性，从这种植物中分离出的两种化合物也在体外进行了评估。原花青素（PAC）是一种含有表儿茶素的二聚体，对 MAYV 感染的 50%细胞的有效浓度（EC）为 37.9±2.4μM，选择性指数（SI）超过 40。PAC 表现出显著的病毒杀伤活性，可抑制 100%的病毒增殖（7 个对数单位），并在吸附和病毒内化阶段产生中度影响。然而，当仅对细胞进行预处理时，PAC 无法阻止感染。当在感染后不同时间点添加 PAC 时，观察到病毒产量减少。这一系列结果表明，PAC 与病毒和非细胞元素结合，并可能使 MAYV 失活。这种失活发生在感染之前，或者当病毒从感染的第二轮到达细胞外环境时，这可能阻止其向未感染的细胞或组织传播。