title: The clinically approved antiviral drug sofosbuvir inhibits Zika virus replication.
abstract: Zika virus (ZIKV) is a member of the Flaviviridae family, along with other agents of clinical significance such as dengue (DENV) and hepatitis C (HCV) viruses. Since ZIKV causes neurological disorders during fetal development and in adulthood, antiviral drugs are necessary. Sofosbuvir is clinically approved for use against HCV and targets the protein that is most conserved among the members of the Flaviviridae family, the viral RNA polymerase. Indeed, we found that sofosbuvir inhibits ZIKV RNA polymerase, targeting conserved amino acid residues. Sofosbuvir inhibited ZIKV replication in different cellular systems, such as hepatoma (Huh-7) cells, neuroblastoma (SH-Sy5y) cells, neural stem cells (NSC) and brain organoids. In addition to the direct inhibition of the viral RNA polymerase, we observed that sofosbuvir also induced an increase in A-to-G mutations in the viral genome. Together, our data highlight a potential secondary use of sofosbuvir, an anti-HCV drug, against ZIKV.
authors.affiliation: Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil.|Instituto Nacional de Infectologia (INI), Fiocruz, Rio de Janeiro, RJ, Brazil.|National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Fiocruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Carolina Q
authors.initials: CQ
authors.lastname: Sacramento
authors.affiliation: Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil.|Instituto Nacional de Infectologia (INI), Fiocruz, Rio de Janeiro, RJ, Brazil.|National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Fiocruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Gabrielle R
authors.initials: GR
authors.lastname: de Melo
authors.affiliation: Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil.|Instituto Nacional de Infectologia (INI), Fiocruz, Rio de Janeiro, RJ, Brazil.|National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Fiocruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Caroline S
authors.initials: CS
authors.lastname: de Freitas
authors.affiliation: Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil.|Instituto Nacional de Infectologia (INI), Fiocruz, Rio de Janeiro, RJ, Brazil.|National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Fiocruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Natasha
authors.initials: N
authors.lastname: Rocha
authors.affiliation: Instituto de Tecnologia de Fármacos (Farmanguinhos), Fiocruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Lucas Villas Bôas
authors.initials: LV
authors.lastname: Hoelz
authors.affiliation: Laboratório de Vírus Respiratório e do Sarampo, IOC, Fiocruz, Rio de Janeiro, RJ, Brazil.|Instituto de Biologia, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil.
authors.forename: Milene
authors.initials: M
authors.lastname: Miranda
authors.affiliation: Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil.|Instituto Nacional de Infectologia (INI), Fiocruz, Rio de Janeiro, RJ, Brazil.|National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Fiocruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Natalia
authors.initials: N
authors.lastname: Fintelman-Rodrigues
authors.affiliation: Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil.|Instituto Nacional de Infectologia (INI), Fiocruz, Rio de Janeiro, RJ, Brazil.|National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Fiocruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Andressa
authors.initials: A
authors.lastname: Marttorelli
authors.affiliation: Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil.|Instituto Nacional de Infectologia (INI), Fiocruz, Rio de Janeiro, RJ, Brazil.|National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Fiocruz, Rio de Janeiro, RJ, Brazil.
authors.forename: André C
authors.initials: AC
authors.lastname: Ferreira
authors.affiliation: Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil.|Instituto Nacional de Infectologia (INI), Fiocruz, Rio de Janeiro, RJ, Brazil.|National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Fiocruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Giselle
authors.initials: G
authors.lastname: Barbosa-Lima
authors.affiliation: Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil.|Instituto Nacional de Infectologia (INI), Fiocruz, Rio de Janeiro, RJ, Brazil.|Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Juliana L
authors.initials: JL
authors.lastname: Abrantes
authors.affiliation: Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil.|Instituto Nacional de Infectologia (INI), Fiocruz, Rio de Janeiro, RJ, Brazil.|National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Fiocruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Yasmine Rangel
authors.initials: YR
authors.lastname: Vieira
authors.affiliation: Instituto de Tecnologia de Fármacos (Farmanguinhos), Fiocruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Mônica M
authors.initials: MM
authors.lastname: Bastos
authors.affiliation: Laboratório de Virologia Comparada e Ambiental, IOC, Fiocruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Eduardo
authors.initials: E
authors.lastname: de Mello Volotão
authors.affiliation: Instituto Nacional de Infectologia (INI), Fiocruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Estevão Portela
authors.initials: EP
authors.lastname: Nunes
authors.affiliation: Instituto de Biologia, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil.|SAGE -COPPE, UFRJ, Rio de Janeiro, RJ, Brazil.|Núcleo em Ecologia e Desenvolvimento Sócio-Ambiental de Macaé (NUPEM), Universidade Federal do Rio de Janeiro, Macaé, Rio de Janeiro, Brazil.
authors.forename: Diogo A
authors.initials: DA
authors.lastname: Tschoeke
authors.affiliation: Instituto de Biologia, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil.|SAGE -COPPE, UFRJ, Rio de Janeiro, RJ, Brazil.
authors.forename: Luciana
authors.initials: L
authors.lastname: Leomil
authors.affiliation: D'Or Institute for Research and Education (IDOR), Rio de Janeiro, RJ, Brazil.
authors.forename: Erick Correia
authors.initials: EC
authors.lastname: Loiola
authors.affiliation: D'Or Institute for Research and Education (IDOR), Rio de Janeiro, RJ, Brazil.
authors.forename: Pablo
authors.initials: P
authors.lastname: Trindade
authors.affiliation: Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.|D'Or Institute for Research and Education (IDOR), Rio de Janeiro, RJ, Brazil.
authors.forename: Stevens K
authors.initials: SK
authors.lastname: Rehen
authors.affiliation: Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil.|Instituto Nacional de Infectologia (INI), Fiocruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Fernando A
authors.initials: FA
authors.lastname: Bozza
authors.affiliation: Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil.
authors.forename: Patrícia T
authors.initials: PT
authors.lastname: Bozza
authors.affiliation: Instituto de Tecnologia de Fármacos (Farmanguinhos), Fiocruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Nubia
authors.initials: N
authors.lastname: Boechat
authors.affiliation: Instituto de Biologia, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil.|SAGE -COPPE, UFRJ, Rio de Janeiro, RJ, Brazil.
authors.forename: Fabiano L
authors.initials: FL
authors.lastname: Thompson
authors.affiliation: Laboratório de Flavivírus, IOC, Fiocruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Ana M B
authors.initials: AM
authors.lastname: de Filippis
authors.affiliation: BMK Consortium: Blanver Farmoquímica Ltda; Microbiológica Química e FarmacêuticaLtda; Karin Bruning &Cia, Ltda, Brazil.
authors.forename: Karin
authors.initials: K
authors.lastname: Brüning
authors.affiliation: Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil.|Instituto Nacional de Infectologia (INI), Fiocruz, Rio de Janeiro, RJ, Brazil.|National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Fiocruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Thiago Moreno L
authors.initials: TM
authors.lastname: Souza
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016679:Genome, Viral; D006801:Humans; D009154:Mutation; D000069474:Sofosbuvir / Q000494:pharmacology* / Q000627:therapeutic use; D014764:Viral Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects*; D000071244:Zika Virus / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D000071243:Zika Virus Infection / Q000188:drug therapy / Q000473:pathology / Q000821:virology
chemical_list: D000998:Antiviral Agents; D014764:Viral Proteins; D012321:DNA-Directed RNA Polymerases; D000069474:Sofosbuvir