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The clinically approved antiviral drug sofosbuvir impairs brazilian zika virus replication

Caroline Q. Sacramento, Gabrielle R. de Melo, Natasha Rocha, Lucas Villas Bôas Hoelz, Milene Mesquita, Caroline S. de Freitas, Natalia Fintelman Rodrigues, Andressa Marttorelli, André C. Ferreiral, Giselle Barbosa-Lima, Mônica M. Bastos, Eduardo de Mello Volotão, Diogo A. Tschoeke, Luciana Leomil, Fernando A. Bozza, Patrícia T. Bozza, Nubia Boechat, Fabiano L. Thompson, Ana M. B. de Filippis, Karin Brüning, Thiago Moreno L. Souza
doi: https://doi.org/10.1101/061671
Caroline Q. Sacramento
1Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil
5Instituto Nacional de Infectologia (INI), Fiocruz, Rio de Janeiro, RJ, Brazil
10National 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
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Gabrielle R. de Melo
1Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil
5Instituto Nacional de Infectologia (INI), Fiocruz, Rio de Janeiro, RJ, Brazil
10National 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
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Natasha Rocha
1Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil
5Instituto Nacional de Infectologia (INI), Fiocruz, Rio de Janeiro, RJ, Brazil
10National 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
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Lucas Villas Bôas Hoelz
6Instituto de Tecnologia de Fármacos (Farmanguinhos), Fiocruz, Rio de Janeiro, RJ, Brazil
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Milene Mesquita
4Laboratório de Vírus Respiratório e do Sarampo, IOC, Fiocruz, Rio de Janeiro, RJ, Brazil
8Instituto de Biologia, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil
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Caroline S. de Freitas
1Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil
5Instituto Nacional de Infectologia (INI), Fiocruz, Rio de Janeiro, RJ, Brazil
10National 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
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Natalia Fintelman Rodrigues
1Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil
5Instituto Nacional de Infectologia (INI), Fiocruz, Rio de Janeiro, RJ, Brazil
10National 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
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Andressa Marttorelli
1Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil
5Instituto Nacional de Infectologia (INI), Fiocruz, Rio de Janeiro, RJ, Brazil
10National 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
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André C. Ferreiral
1Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil
5Instituto Nacional de Infectologia (INI), Fiocruz, Rio de Janeiro, RJ, Brazil
10National 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
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Giselle Barbosa-Lima
1Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil
5Instituto Nacional de Infectologia (INI), Fiocruz, Rio de Janeiro, RJ, Brazil
10National 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
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Mônica M. Bastos
6Instituto de Tecnologia de Fármacos (Farmanguinhos), Fiocruz, Rio de Janeiro, RJ, Brazil
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Eduardo de Mello Volotão
2Laboratório de Virologia Comparada e Ambiental, IOC, Fiocruz, Rio de Janeiro, RJ, Brazil
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Diogo A. Tschoeke
8Instituto de Biologia, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil
9SAGECOPPE, UFRJ, Rio de Janeiro RJ, Brazil
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Luciana Leomil
8Instituto de Biologia, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil
9SAGECOPPE, UFRJ, Rio de Janeiro RJ, Brazil
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Fernando A. Bozza
1Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil
5Instituto Nacional de Infectologia (INI), Fiocruz, Rio de Janeiro, RJ, Brazil
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Patrícia T. Bozza
1Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil
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Nubia Boechat
6Instituto de Tecnologia de Fármacos (Farmanguinhos), Fiocruz, Rio de Janeiro, RJ, Brazil
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Fabiano L. Thompson
8Instituto de Biologia, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil
9SAGECOPPE, UFRJ, Rio de Janeiro RJ, Brazil
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Ana M. B. de Filippis
3Laboratório de Flavivírus, IOC, Fiocruz, Rio de Janeiro, RJ, Brazil
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Karin Brüning
7BMK Consortium: Blanver Farmoquímica Ltda; Microbiológica 25 Química e Farmacêutica Ltda; Karin Bruning & Cia. Ltda, Brazil
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Thiago Moreno L. Souza
1Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil
5Instituto Nacional de Infectologia (INI), Fiocruz, Rio de Janeiro, RJ, Brazil
10National 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
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  • For correspondence: tmoreno@cdts.fiocruz.br
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Summary

Zika virus (ZIKV) is a member of Flaviviridae family, as other agents of clinical significance, such as dengue (DENV) and hepatitis C (HCV) viruses. ZIKV spread from Africa to Pacific and South American territories, emerging as an etiological pathogen of neurological disorders, during fetal development and in adulthood. Therefore, antiviral drugs able to inhibit ZIKV replication are necessary. Broad spectrum antivirals, such as interferon, ribavirin and favipiravir, are harmful for pregnant animal models and women. The clinically approved uridine nucleotide analog anti-HCV drug, sofosbuvir, has not been affiliated to teratogenicity. Sofosbuvir target the most conserved protein over the members of the Flaviviridae family, the viral RNA polymerase. We thus studied ZIKV susceptibility to sofosbovir. We initially characterized a Brazilian ZIKV strain for use in experimental assays. Sofosbuvir inhibits the Brazilian ZIKV replication in a dose-dependent manner, both in BHK-21 cells and SH-Sy5y, by targeting ZIKV RNA polymerase activity, with the involvement of conserved amino acid residues over the members of Flaviviridae family. The identification of clinically approved antiviral drugs endowed with anti-ZIKV could reduce the time frame in pre-clinical development. Altogether, our data indicates that sofosbuvir chemical structure is endowed with anti-ZIKV activity.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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The clinically approved antiviral drug sofosbuvir impairs brazilian zika virus replication
Caroline Q. Sacramento, Gabrielle R. de Melo, Natasha Rocha, Lucas Villas Bôas Hoelz, Milene Mesquita, Caroline S. de Freitas, Natalia Fintelman Rodrigues, Andressa Marttorelli, André C. Ferreiral, Giselle Barbosa-Lima, Mônica M. Bastos, Eduardo de Mello Volotão, Diogo A. Tschoeke, Luciana Leomil, Fernando A. Bozza, Patrícia T. Bozza, Nubia Boechat, Fabiano L. Thompson, Ana M. B. de Filippis, Karin Brüning, Thiago Moreno L. Souza
bioRxiv 061671; doi: https://doi.org/10.1101/061671
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The clinically approved antiviral drug sofosbuvir impairs brazilian zika virus replication
Caroline Q. Sacramento, Gabrielle R. de Melo, Natasha Rocha, Lucas Villas Bôas Hoelz, Milene Mesquita, Caroline S. de Freitas, Natalia Fintelman Rodrigues, Andressa Marttorelli, André C. Ferreiral, Giselle Barbosa-Lima, Mônica M. Bastos, Eduardo de Mello Volotão, Diogo A. Tschoeke, Luciana Leomil, Fernando A. Bozza, Patrícia T. Bozza, Nubia Boechat, Fabiano L. Thompson, Ana M. B. de Filippis, Karin Brüning, Thiago Moreno L. Souza
bioRxiv 061671; doi: https://doi.org/10.1101/061671

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