Memorias do Instituto Oswaldo Cruz · 2026
Enhancement of simeprevir and sofosbuvir anti-ZIKV activity by iNOS-derived NO in vitroFIRST REVIEW ROUND - REVIEWERS' COMMENTSREVIEWERS' COMMENTS.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Soares-Bezerra Rômulo José, Charret Karen Dos Santos, da Silva João Marcos Beserra Rocha, Mamprim Joana Miranda, Leite Lucas de Souza, Lima Richard de Almeida, Rodrigues Daniela Del Rosário Flores, da Silva Alexandre Dos Santos, Ferreira Natiele Carla da Silva, Pinto Marcelo Alves
Аннотация
BACKGROUND: Zika virus (ZIKV) was first identified in the Americas in 2015, with Brazil experiencing a major epidemic marked by teratogenic effects during early pregnancy. Ex vivo studies of microglia from fatal ZIKV-induced microcephaly cases revealed elevated levels of inducible nitric oxide synthase (iNOS) and nitric oxide (NO). Direct-acting antivirals (DAAs) have been proposed as potential ZIKV treatments.
OBJECTIVES: This study aimed to investigate the effects of two DAAs, simeprevir and sofosbuvir, on iNOS expression and NO production during in vitro ZIKV infection.
METHODS: Molecular docking analyses were performed to assess the interaction between DAAs and the iNOS enzyme. ZIKV-infected Vero CCL-81 cells were treated with simeprevir or sofosbuvir (10 µmol/L), and iNOS expression, NO production, and cytotoxicity were evaluated.
FINDINGS: Both DAAs demonstrated strong binding affinity to the iNOS active site. Compared with the untreated infected controls, treatment with simeprevir and sofosbuvir significantly upregulated iNOS expression and increased NO production by approximately 60%. No cytotoxic effects were observed under the experimental conditions.
MAIN CONCLUSIONS: Simeprevir and sofosbuvir not only exhibit antiviral properties but also may enhance the host antiviral response via modulation of the NO pathway, suggesting a dual mechanism of action against ZIKV.
OBJECTIVES: This study aimed to investigate the effects of two DAAs, simeprevir and sofosbuvir, on iNOS expression and NO production during in vitro ZIKV infection.
METHODS: Molecular docking analyses were performed to assess the interaction between DAAs and the iNOS enzyme. ZIKV-infected Vero CCL-81 cells were treated with simeprevir or sofosbuvir (10 µmol/L), and iNOS expression, NO production, and cytotoxicity were evaluated.
FINDINGS: Both DAAs demonstrated strong binding affinity to the iNOS active site. Compared with the untreated infected controls, treatment with simeprevir and sofosbuvir significantly upregulated iNOS expression and increased NO production by approximately 60%. No cytotoxic effects were observed under the experimental conditions.
MAIN CONCLUSIONS: Simeprevir and sofosbuvir not only exhibit antiviral properties but also may enhance the host antiviral response via modulation of the NO pathway, suggesting a dual mechanism of action against ZIKV.