Amorim Raquel, de Meneses Marcelo Damião Ferreira, Borges Julio Cesar, da Silva Pinheiro Luiz Carlos, Caldas Lucio Ayres, Cirne-Santos Claudio Cesar, de Mello Marcos Vinícius Palmeira, de Souza Alessandra Mendonça Teles, Castro Helena Carla, de Palmer Paixão Izabel Christina Nunes, Campos Renata de Mendonça, Bergmann Ingrid E, Malirat Viviana, Bernardino Alice Maria Rolim, Rebello Moacyr Alcoforado, Ferreira Davis Fernandes
Departamento de Virologia, Instituto de Microbiologia, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, Rio de Janeiro, 21941-902, Brazil.
Instituto Federal de Educação, Ciência e Tecnologia do Rio de Janeiro, Campus Nilópolis, Nilópolis, 26530-060, Brazil.
Arch Virol. 2017 Jun;162(6):1577-1587. doi: 10.1007/s00705-017-3261-0. Epub 2017 Feb 17.
Mayaro virus (MAYV) is an arthropod-borne virus and a member of the family Togaviridae, genus Alphavirus. Its infection leads to an acute illness accompanied by long-lasting arthralgia. To date, there are no antiviral drugs or vaccines against infection with MAYV and resources for the prevention or treatment of other alphaviruses are very limited. MAYV has served as a model to study the antiviral potential of several substances on alphavirus replication. In this work we evaluated the antiviral effect of seven new derivatives of thieno[2,3-b]pyridine against MAYV replication in a mammalian cell line. All derivatives were able to reduce viral production effectively at concentrations that were non-toxic for Vero cells. Molecular modeling assays predicted low toxicity risk and good oral bioavailability of the substances in humans. One of the molecules, selected for further study, demonstrated a strong anti-MAYV effect at early stages of replication, as it protected pre-treated cells and also during the late stages, affecting virus morphogenesis. This study is the first to demonstrate the antiviral effect of thienopyridine derivatives on MAYV replication in vitro, suggesting the potential application of these substances as antiviral molecules against alphaviruses. Additional in vivo research will be needed to expand the putative therapeutic applications.
马亚罗病毒（MAYV）是一种节肢动物传播病毒，属于披膜病毒科甲病毒属。其感染会导致一种伴有长期关节痛的急性疾病。迄今为止，尚无针对MAYV感染的抗病毒药物或疫苗，且用于预防或治疗其他甲病毒的资源非常有限。MAYV已成为研究几种物质对甲病毒复制抗病毒潜力的模型。在这项工作中，我们评估了噻吩并[2,3 - b]吡啶的七种新衍生物对哺乳动物细胞系中MAYV复制的抗病毒作用。所有衍生物在对Vero细胞无毒的浓度下均能有效降低病毒产量。分子建模分析预测这些物质在人体中的毒性风险低且口服生物利用度良好。选择进一步研究的其中一种分子在复制早期表现出强大的抗MAYV作用，因为它能保护预处理的细胞，在后期也有作用，影响病毒形态发生。本研究首次证明噻吩并吡啶衍生物对MAYV体外复制的抗病毒作用，表明这些物质作为抗甲病毒的抗病毒分子具有潜在应用价值。需要进行更多的体内研究以扩大假定的治疗应用范围。
