title: Thieno[2,3-b]pyridine derivatives: a new class of antiviral drugs against Mayaro virus.
abstract: 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.
authors.affiliation: 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.
authors.forename: Raquel
authors.initials: R
authors.lastname: Amorim
authors.affiliation: 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.
authors.forename: Marcelo Damião Ferreira
authors.initials: MDF
authors.lastname: de Meneses
authors.affiliation: Instituto Federal de Educação, Ciência e Tecnologia do Rio de Janeiro, Campus Nilópolis, Nilópolis, 26530-060, Brazil.
authors.forename: Julio Cesar
authors.initials: JC
authors.lastname: Borges
authors.affiliation: Departamento de Síntese de Fármacos, Instituto de Tecnologia em Fármacos, Farmanguinhos-FIOCRUZ, Rio de Janeiro, 21041-250, Brazil.
authors.forename: Luiz Carlos
authors.initials: LC
authors.lastname: da Silva Pinheiro
authors.affiliation: Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, Rio de Janeiro, 21941-902, Brazil.
authors.forename: Lucio Ayres
authors.initials: LA
authors.lastname: Caldas
authors.affiliation: 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.
authors.forename: Claudio Cesar
authors.initials: CC
authors.lastname: Cirne-Santos
authors.affiliation: Laboratório de Antibióticos, Bioquímica, Educação e Modelagem Molecular, Universidade Federal Fluminense, Campus Valonguinho, Outeiro de São João Batista s/n°, Niterói, Rio de Janeiro, 24020-150, Brazil.
authors.forename: Marcos Vinícius Palmeira
authors.initials: MVP
authors.lastname: de Mello
authors.affiliation: Laboratório de Modelagem Molecular e QSAR, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, CEP 21941-590, Brazil.
authors.forename: Alessandra Mendonça Teles
authors.initials: AMT
authors.lastname: de Souza
authors.affiliation: Laboratório de Antibióticos, Bioquímica, Educação e Modelagem Molecular, Universidade Federal Fluminense, Campus Valonguinho, Outeiro de São João Batista s/n°, Niterói, Rio de Janeiro, 24020-150, Brazil.
authors.forename: Helena Carla
authors.initials: HC
authors.lastname: Castro
authors.affiliation: Laboratório de Virologia Molecular e Biotecnologia Marinha, Programa, Departamento de Biologia Celular e Molecular, Instituto de Biologia, Universidade Federal Fluminense, Niterói, Brazil.
authors.forename: Izabel Christina Nunes
authors.initials: ICN
authors.lastname: de Palmer Paixão
authors.affiliation: 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.
authors.forename: Renata de Mendonça
authors.initials: RM
authors.lastname: Campos
authors.affiliation: Centro de Virología Animal (CEVAN), Instituto de Ciencia y Tecnología Dr. César Milstein, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Saladillo 2468, CP: 1440, Buenos Aires, Argentina.
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Bergmann
authors.affiliation: Centro de Virología Animal (CEVAN), Instituto de Ciencia y Tecnología Dr. César Milstein, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Saladillo 2468, CP: 1440, Buenos Aires, Argentina.
authors.forename: Viviana
authors.initials: V
authors.lastname: Malirat
authors.affiliation: Departamento de Química Orgânica, Instituto de Química, Universidade Federal Fluminense, Outeiro de São João Batista, s/n, Centro, Niterói, Rio de Janeiro, 24020-141, Brazil.
authors.forename: Alice Maria Rolim
authors.initials: AMR
authors.lastname: Bernardino
authors.affiliation: 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.
authors.forename: Moacyr Alcoforado
authors.initials: MA
authors.lastname: Rebello
authors.affiliation: 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. davisf@micro.ufrj.br.
authors.forename: Davis Fernandes
authors.initials: DF
authors.lastname: Ferreira
mesh_terms: D000524:Alphavirus / Q000187:drug effects*; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D006801:Humans; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D011725:Pyridines; D013876:Thiophenes