Feferbaum-Leite Shiraz, Marques Cassani Natasha, Aquino Ruiz Uriel Enrique, Clemente Dias Renieidy Flávia, Nascimento Farago Danilo, Guevara-Vega Marco, Nicolau-Junior Nilson, Sabino-Silva Robinson, Rezende Júnior Celso de Oliveira, Jardim Ana Carolina Gomes
Laboratory of Antiviral Research (LAPAV), Institute of Biomedical Science (ICBIM), Federal University of Uberlândia (UFU), Uberlândia, Minas Gerais, Brazil.
Drug Candidate Synthesis Laboratory (LaSFar), Institute of Chemistry, Federal University of Uberlândia (UFU), Uberlândia, Minas Gerais, Brazil.
Future Med Chem. 2025 May;17(10):1105-1117. doi: 10.1080/17568919.2025.2504337. Epub 2025 May 16.
Chikungunya virus (CHIKV) is the agent of chikungunya fever (CHIKF), a reemerging disease prevalent in tropical regions. With no licensed treatments available, identifying effective antiviral compounds is critical. This study evaluates the antiviral potential of 20 synthetic sulfonamide derivatives against CHIKV.
We tested 13 heteroaromatic derivatives containing thiazole, benzimidazole, and benzothiazole (BTA) moieties, along with seven sulfonamides bearing ester and carboxylic acid groups. CHIKV- replication was assessed , and molecular docking and infrared spectroscopy studies were conducted to explore interactions with viral proteins.
BTA derivatives 6, 9, 11, and 13 demonstrated potent CHIKV inhibition, with EC values between 14.9 and 63.1 µM and selective indexes of 13.8, 5.8, 4.4, and 11, respectively. All compounds acted in the virus post-entry stage, with compound 9 reducing viral replication by 98%. Compound 9 exhibited multi-stage activity, inhibiting CHIKV through virucidal (55%), pre-treatment (69%), and entry (98%) mechanisms. Molecular docking suggested strong binding affinities to CHIKV non-structural proteins and envelope glycoproteins. Infrared spectroscopy corroborated compound 9's interaction with the glycoprotein complex and lipids.
These findings highlight BTA derivatives as promising CHIKV inhibitors. Compound 9's ability to interfere at multiple stages of infection suggests its potential for therapeutic development against CHIKF.
基孔肯雅病毒（CHIKV）是基孔肯雅热（CHIKF）的病原体，这是一种在热带地区流行的再度出现的疾病。由于没有可用的许可治疗方法，鉴定有效的抗病毒化合物至关重要。本研究评估了20种合成磺酰胺衍生物对CHIKV的抗病毒潜力。
我们测试了13种含有噻唑、苯并咪唑和苯并噻唑（BTA）部分的杂芳族衍生物，以及7种带有酯和羧酸基团的磺酰胺。评估了CHIKV的复制，并进行了分子对接和红外光谱研究以探索与病毒蛋白的相互作用。
BTA衍生物6、9、11和13表现出强大的CHIKV抑制作用，EC值在14.9至63.1μM之间，选择性指数分别为13.8、5.8、4.4和11。所有化合物均在病毒进入后阶段起作用，化合物9使病毒复制减少了98%。化合物9表现出多阶段活性，通过杀病毒（55%）、预处理（69%）和进入（98%）机制抑制CHIKV。分子对接表明与CHIKV非结构蛋白和包膜糖蛋白具有很强的结合亲和力。红外光谱证实了化合物9与糖蛋白复合物和脂质的相互作用。
这些发现突出了BTA衍生物作为有前景的CHIKV抑制剂。化合物9在感染的多个阶段进行干扰的能力表明其在开发针对CHIKF的治疗方法方面具有潜力。
