PAV-05 Naphthoquinone Potently Inhibit Zika Virus Replication in Infected Cells

Claudio Cesar Cirne-Santos; Daniel Tadeu Gomes Gonzaga; Gabriel Oliveira de Resende; Mariana de Castro Gonçalves; Aymee da Silva Andrade; Paulo Anastácio Furtado Pacheco; Alexandre Dos Santos-Rodrigues; Vitor Won-Held Rabelo; Paula Alvarez Abreu; Robson Xavier Faria; David Rodrigues da Rocha; Fernando de Carvalho da Silva; Vitor Francisco Ferreira; Caroline de Souza Barros; Izabel Christina Nunes de Palmer Paixão

doi:10.2174/0115680266323907241212062715

PAV-05 Naphthoquinone Potently Inhibit Zika Virus Replication in Infected Cells

Curr Top Med Chem. 2025 Jan 21. doi: 10.2174/0115680266323907241212062715. Online ahead of print.

Authors

Claudio Cesar Cirne-Santos^{1

2}, Daniel Tadeu Gomes Gonzaga³, Gabriel Oliveira de Resende⁴, Mariana de Castro Gonçalves⁵, Aymee da Silva Andrade^{1

2}, Paulo Anastácio Furtado Pacheco⁶, Alexandre Dos Santos-Rodrigues⁷, Vitor Won-Held Rabelo^{1

8}, Paula Alvarez Abreu⁹, Robson Xavier Faria⁴, David Rodrigues da Rocha⁵, Fernando de Carvalho da Silva⁵, Vitor Francisco Ferreira¹⁰, Caroline de Souza Barros^{2

8

11}, Izabel Christina Nunes de Palmer Paixão^{1

8

8}

Affiliations

¹ Universidade Federal Fluminense, Instituto de Biologia, Laboratório de Virologia Molecular e Biotecnologia Marinha, 24210-200, Niterói-RJ, Brasil.
² Programa de Pós-graduação em Ciências e Biotecnologia (PPBI), Instituto de Biologia, Universidade Federal Fluminense, 24210-200, Niterói, RJ, Brasil.
³ Universidade do Estado do Rio de Janeiro, FCBS, DEPFARM, Rio de Janeiro, Brasil.
⁴ Instituto Oswaldo Cruz, Laboratório de Comunicação Celular, Fundação Oswaldo Cruz, RJ Brazil.
⁵ Universidade Federal Fluminense, Instituto de Química, Departamento de Química Orgânica, 24210-141, Niterói-RJ, Brasil.
⁶ Universidade Federal do Rio de Janeiro, Instituto de Biodiversidade e Sustentabilidade, Macaé, RJ, CEP 27965-045, Brasil.
⁷ Universidade Federal Fluminense,Instituto de Biologia, Departamento de Neurobiologia, Programa de Pós-Graduação em Neurociências, Instituto de Biologia, Niterói, Brasil.
⁸ Programa de Pós-Graduação em Biotecnogia Marinha, Instituto de Biologia, Universidade Federal Fluminense, 24210-200, Niterói, RJ, Brasil.
⁹ Universidade Federal do Rio de Janeiro, Instituto de Biodiversidade e Sustentabilidade Instituto de Biodiversidade e Sustentabilidade Niterói Brazil.
¹⁰ Universidade Federal Fluminense, Faculdade de Farmácia, Departamento de Tecnologia Farmacêutica, CEP 24241-000 Niterói, RJ, Brazil.
¹¹ Universidade Federal Fluminense, Instituto de Biologia, Departamento de Imunobiologia, Laboratório de Imunovirologia, 24210-200, Niterói-RJ, Brasil.

PMID: 39844553
DOI: 10.2174/0115680266323907241212062715

Abstract

Background: Zika (ZIKV) is a virus transmitted by mosquitoes that can cause Guillain- Barré syndrome and congenital malformations like microcephaly. Given its explosive resurgence and the resulting epidemics in 2016, the search for effective antiviral drugs has become absolutely necessary.

Methods: In this study, we examined the potential of naphthoquinone derivatives that have a sulfonamide or sulfonate group to inhibit ZIKV replication in primary cultured neurons and in Vero cells.

Results: In our in vitro studies, we found that PAV05 had low cytotoxicity with a CC50 of 329 μM ±3.6 for Vero cells and 290 μM ±3.5 for neurons. Additionally, we observed a strong inhibitory activity on viral replication with an EC50 value of EC50 of 0.92 μM ±0.15 in Vero cells, resulting in a Selectivity Index (SI) of 357. Even when added 16 hours post-infection, PAV05 maintained its inhibitory effect. When PAV05 was evaluated in sub-optimal concentrations together with Ribavirin, we observed a strong synergistic effect, with an inhibition greater than 90% even at doses of 0.5 μM. In silico tests suggested that PAV05 may have effects on ZIKV NS2B-NS3.

Conclusion: The ZIKV inhibitor described in this study shows promise as a compound for the development of therapies against ZIKV. It may also be considered for inclusion in the portfolio of broad-spectrum antiflavivirus inhibitors.

Keywords: Arbovirus.; Naphthoquinone; Antiviral; ZIKA-Virus.