Ayusso Gabriela Miranda, da Silva Sanches Paulo Ricardo, Carvalho Tamara, Santos Igor Andrade, Martins Daniel Oliveira Silva, Lima Maria Letícia Duarte, da Conceição Pâmela Jóyce Previdelli, Bittar Cíntia, Merits Andres, Cilli Eduardo Maffud, Jardim Ana Carolina Gomes, Rahal Paula, Calmon Marilia Freitas
Institute of Biosciences, Letters and Exact Sciences, São Paulo State University, São José do Rio Preto 15054-000, SP, Brazil.
School of Pharmaceutical Sciences, São Paulo State University, Araraquara 14800-903, SP, Brazil.
Pharmaceuticals (Basel). 2023 Sep 30;16(10):1389. doi: 10.3390/ph16101389.
Chikungunya virus (CHIKV) belongs to the genus and is responsible for significant outbreaks worldwide. Currently, there is no approved antiviral therapy against CHIKV. Bioactive peptides have great potential for new drug development. Here, we evaluated the antiviral activity of the synthetic peptide GA-Hecate and its analogs PSSct1905 and PSSct1910 against CHIKV infection. Initial screening showed that all three peptides inhibited the CHIKV replication cycle in baby hamster kidney fibroblast cells (BHK-21) and human hepatocarcinoma epithelial cells (Huh-7). GA-Hecate and its analog PSSct1905 were the most active, demonstrating suppression of viral infection by more than 91%. The analog PSSct1905 exhibited a protective effect in cells against CHIKV infection. We also observed that the analogs PSSct1905 and PSSct1910 affected CHIKV entry into both cell lines, inhibiting viral attachment and internalization. Finally, all tested compounds presented antiviral activity on the post-entry steps of CHIKV infection in all cells evaluated. In conclusion, this study highlights the potential of the peptide GA-Hecate and its analogs as novel anti-CHIKV compounds targeting different stages of the viral replication cycle, warranting the development of GA-Hecate-based compounds with broad antiviral activity.
基孔肯雅病毒（CHIKV）属于该属，在全球范围内引发了重大疫情。目前，尚无针对CHIKV的获批抗病毒疗法。生物活性肽在新药开发方面具有巨大潜力。在此，我们评估了合成肽GA-Hecate及其类似物PSSct1905和PSSct1910对CHIKV感染的抗病毒活性。初步筛选表明，所有这三种肽均抑制了幼仓鼠肾成纤维细胞（BHK-21）和人肝癌上皮细胞（Huh-7）中的CHIKV复制周期。GA-Hecate及其类似物PSSct1905活性最强，对病毒感染的抑制率超过91%。类似物PSSct1905在细胞中对CHIKV感染表现出保护作用。我们还观察到，类似物PSSct1905和PSSct1910影响CHIKV进入这两种细胞系，抑制病毒附着和内化。最后，所有测试化合物在所有评估细胞中对CHIKV感染的进入后步骤均呈现抗病毒活性。总之，本研究突出了肽GA-Hecate及其类似物作为靶向病毒复制周期不同阶段的新型抗CHIKV化合物的潜力，这为开发具有广泛抗病毒活性的基于GA-Hecate的化合物提供了依据。
