Current topics in medicinal chemistry · 2025
PAV-05 Naphthoquinone Potently Inhibit Zika Virus Replication in Infected Cells.
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Cirne-Santos Claudio Cesar, Gonzaga Daniel Tadeu Gomes, de Resende Gabriel Oliveira, de Castro Goncalves Mariana, da Silva Andrade Aymee, Furtado Pacheco Paulo Anastacio, Dos Santos-Rodrigues Alexandre, Rabelo Vitor Won-Held, Abreu Paula Alvarez, Faria Robson Xavier, da Rocha David Rodrigues, da Silva Fernando de Carvalho, Ferreira Vitor Francisco, de Souza Barros Caroline, de Palmer Paixao Izabel Christina Nunes
Аннотация
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.
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.