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
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引用次数: 0
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.
期刊介绍：
Current Topics in Medicinal Chemistry is a forum for the review of areas of keen and topical interest to medicinal chemists and others in the allied disciplines. Each issue is solely devoted to a specific topic, containing six to nine reviews, which provide the reader a comprehensive survey of that area. A Guest Editor who is an expert in the topic under review, will assemble each issue. The scope of Current Topics in Medicinal Chemistry will cover all areas of medicinal chemistry, including current developments in rational drug design, synthetic chemistry, bioorganic chemistry, high-throughput screening, combinatorial chemistry, compound diversity measurements, drug absorption, drug distribution, metabolism, new and emerging drug targets, natural products, pharmacogenomics, and structure-activity relationships. Medicinal chemistry is a rapidly maturing discipline. The study of how structure and function are related is absolutely essential to understanding the molecular basis of life. Current Topics in Medicinal Chemistry aims to contribute to the growth of scientific knowledge and insight, and facilitate the discovery and development of new therapeutic agents to treat debilitating human disorders. The journal is essential for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important advances.
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