Institute of Biomedical Science - ICBIM, Federal University of Uberlândia - UFU, Avenida Amazonas, 4C- Room 216, Umuarama, Uberlândia, MG, CEP: 38405-302, Brazil.
Institute of Bioscience, Language and Exact Sciences - IBILCE, São Paulo State University - UNESP, São José do Rio Preto, SP, Brazil.
Pharmacol Rep. 2024 Oct;76(5):1147-1159. doi: 10.1007/s43440-024-00635-z. Epub 2024 Aug 16.
Currently, there is no antiviral licensed to treat chikungunya fever, a disease caused by the infection with Alphavirus chikungunya (CHIKV). Treatment is based on analgesic and anti-inflammatory drugs to relieve symptoms. Our study aimed to evaluate the antiviral activity of sulfadoxine (SFX), an FDA-approved drug, and its derivatives complexed with silver(I) (AgSFX), salicylaldehyde Schiff base (SFX-SL), and with both Ag and SL (AgSFX-SL) against CHIKV.
The anti-CHIKV activity of SFX and its derivatives was investigated using BHK-21 cells infected with CHIKV-nanoluc, a marker virus-carrying nanoluciferase reporter. Dose-response and time of drug-addition assays were performed in order to assess the antiviral effects of the compounds, as well as in silico data and ATR-FTIR analysis for insights on their mechanisms of action.
The SFX inhibited 34% of CHIKV replication, while AgSFX, SFX-SL, and AgSFX-SL enhanced anti-CHIKV activity to 84%, 89%, and 95%, respectively. AgSFX, SFX-SL, and AgSFX-SL significantly decreased viral entry and post-entry to host cells, and the latter also protected cells against infection. Additionally, molecular docking calculations and ATR-FTIR analysis demonstrated interactions of SFX-SL, AgSFX, and AgSFX-SL with CHIKV.
Collectively, our findings suggest that the addition of metal ions and/or Schiff base to SFX improved its antiviral activity against CHIKV.
目前，尚无获许可用于治疗基孔肯雅热的抗病毒药物，基孔肯雅热是由基孔肯雅病毒（CHIKV）感染引起的疾病。治疗方法主要基于使用镇痛和抗炎药物来缓解症状。我们的研究旨在评估磺胺多辛（SFX），一种获得 FDA 批准的药物，及其与银（I）（AgSFX）、水杨醛席夫碱（SFX-SL）复合，以及同时与 Ag 和 SL 复合（AgSFX-SL）的抗 CHIKV 活性。
使用感染 CHIKV-nanoluc 的 BHK-21 细胞（一种携带纳米荧光素酶报告基因的标记病毒）来研究 SFX 和其衍生物的抗 CHIKV 活性。进行剂量反应和加药时间测定，以评估化合物的抗病毒作用，以及使用计算机模拟数据和 ATR-FTIR 分析来了解其作用机制。
SFX 抑制了 34%的 CHIKV 复制，而 AgSFX、SFX-SL 和 AgSFX-SL 则分别增强了抗 CHIKV 活性至 84%、89%和 95%。AgSFX、SFX-SL 和 AgSFX-SL 显著降低了病毒进入宿主细胞的过程以及进入后阶段，后者还能保护细胞免受感染。此外，分子对接计算和 ATR-FTIR 分析表明 SFX-SL、AgSFX 和 AgSFX-SL 与 CHIKV 发生了相互作用。
综上所述，我们的研究结果表明，金属离子和/或席夫碱的添加提高了 SFX 对 CHIKV 的抗病毒活性。
