Thieno[2,3-b]pyridine derivatives: a new class of antiviral drugs against Mayaro virus

Authors
Amorim, Raquel; Meneses, Marcelo Damião Ferreira de; Borges, Julio Cesar; Pinheiro, Luiz Carlos da Silva; Caldas, Lucio Ayres; Cirne Santos, Claudio Cesar; Mello, Marcos Vinícius Palmeira de; Souza, Alessandra Mendonça Teles de; Castro, Helena Carla; Paixão, Izabel Christina Nunes de Palmer; Campos, Renata de Mendonça; Bergmann, Ingrid Evelyn; Malirat, Viviana; Bernardino, Alice Maria Rolim; Rebello, Moacyr Alcoforado; Fernandes Ferreira, Davis
Publication Year
2017
Language
English
Format
article
Status
Published version
Description
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.
Fil: Amorim, Raquel. Universidade Federal do Rio de Janeiro; Brasil
Fil: Meneses, Marcelo Damião Ferreira de. Universidade Federal do Rio de Janeiro; Brasil
Fil: Borges, Julio Cesar. Instituto Federal de Educação, Ciência e Tecnologia do Rio de Janeiro; Brasil
Fil: Pinheiro, Luiz Carlos da Silva. Universidade Federal do Rio de Janeiro; Brasil
Fil: Caldas, Lucio Ayres. Universidade Federal do Rio de Janeiro; Brasil
Fil: Cirne Santos, Claudio Cesar. Universidade Federal do Rio de Janeiro; Brasil
Fil: Mello, Marcos Vinícius Palmeira de. Universidade Federal Fluminense; Brasil
Fil: Souza, Alessandra Mendonça Teles de. Universidade Federal do Rio de Janeiro; Brasil
Fil: Castro, Helena Carla. Universidade Federal Fluminense; Brasil
Fil: Paixão, Izabel Christina Nunes de Palmer. Universidade Federal Fluminense; Brasil
Fil: Campos, Renata de Mendonça. Universidade Federal do Rio de Janeiro; Brasil
Fil: Bergmann, Ingrid Evelyn. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología ; Argentina
Fil: Malirat, Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología ; Argentina
Fil: Bernardino, Alice Maria Rolim. Universidade Federal Fluminense; Brasil
Fil: Rebello, Moacyr Alcoforado. Universidade Federal do Rio de Janeiro; Brasil
Fil: Fernandes Ferreira, Davis. Universidade Federal do Rio de Janeiro; Brasil
Subject
ANTIVIRALES
VIRUS MAYARO
Otras Ciencias Biológicas
Ciencias Biológicas
CIENCIAS NATURALES Y EXACTAS
Access level
Restricted access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/43583