Yellow fever virus is susceptible to sofosbuvir both in vitro and in vivo

de Freitas, C.; Higa, L.; Sacramento, C.; Ferreira, A.; Reis, P.; Delvecchio, R.; Monteiro, F.; Barbosa-Lima, G.; Vieira, Y.; Mattos, M.; Hoelz, L.; Leme, R.; Bastos, M.; Bozza, F.; Bozza, P.; Boechat, N.; Tanuri, A.; Souza, T.

doi:10.1101/266361

bioRxiv · 10.1101/266361

Yellow fever virus is susceptible to sofosbuvir both in vitro and in vivo

de Freitas, C.·Higa, L.·Sacramento, C.·Ferreira, A.·Reis, P.·Delvecchio, R.·Monteiro, F.·Barbosa-Lima, G.·Vieira, Y.·Mattos, M.·Hoelz, L.·Leme, R.·Bastos, M.·Bozza, F.·Bozza, P.·Boechat, N.·Tanuri, A.·Souza, T.

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Abstract

Yellow fever virus (YFV) is a member of the Flaviviridae family, that causes major mortality. In Brazil, YFV activity increased in the last years. It has been registered that sylvatic, instead of urban, yellow fever (YF) leads our contemporary public health concern. Low vaccinal coverage leaves the human population near the jangle vulnerable to the outbreak, making it necessary to identify therapeutic options. Repurposing of clinically approved antiviral drugs represents an alternative for such identification. Other Flaviviruses, such Zika (ZIKV) and dengue (DENV) viruses, are susceptible to Sofosbuvir, a clinically approved drug against hepatitis C virus (HCV). Moreover, sofosbuvir has a safety record on critically ill hepatic patients, making it an attractive option. Our data show that YFV RNA polymerase uses conserved amino acid resides for nucleotide binding to dock sofosbuvir. This drug inhibited YFV replication in different lineages of human hepatoma cells, Huh-7 and HepG2, with EC50 value of 4.8 {micro}M. Sofosbuvir protected YFV-infected neonatal Swiss mice from mortality and weight loss. Our pre-clinical results indicate that sofosbuvir could represent an option against YFV.

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de Freitas, C., Higa, L., Sacramento, C., Ferreira, A., Reis, P., Delvecchio, R., Monteiro, F., Barbosa-Lima, G., Vieira, Y., Mattos, M., Hoelz, L., Leme, R., Bastos, M., Bozza, F., Bozza, P., Boechat, N., Tanuri, A., Souza, T.. 2018-02-15. Yellow fever virus is susceptible to sofosbuvir both in vitro and in vivo. https://doi.org/10.1101/266361

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