Gomes Luana S, Cirne-Santos Claudio C, de S Barros Caroline, Batista Rafael R, de P Ignacio Matheus R, de Oliveira Aldo S, Ronconi Célia M, de Palmer Paixão Izabel C N, Nascimento Vanessa
SupraSelen Laboratory, Department of Organic Chemistry, Universidade Federal Fluminense, Institute of Chemistry, Niterói, RJ, Brazil.
Postgraduate Program in Sciences and Biotechnology (PPBI), Universidade Federal Fluminense, Biology Institute, Niterói, RJ, Brazil.
Future Med Chem. 2025 Jun;17(12):1363-1375. doi: 10.1080/17568919.2025.2525068. Epub 2025 Jul 8.
Emerging arboviruses such as Zika virus (ZIKV) and Chikungunya virus (CHIKV) remain significant public health threats. This study aimed to evaluate the antiviral potential of six organochalcogen compounds against ZIKV and CHIKV.
MATERIALS & METHODS: Compounds were assessed for cytotoxicity and antiviral activity in Vero cells. Antiviral effects were determined using plaque reduction assays, time-of-addition studies, viral adsorption, and virucidal assays. Molecular docking and density functional theory (DFT) calculations were performed to investigate interactions with viral targets and electronic properties.
Compounds , , , and exhibited potent antiviral activity with low cytotoxicity, demonstrating effective inhibition of viral replication with half-maximal effective concentration (EC₅₀) values in the micromolar range and favorable selectivity indices. Mechanistic assays revealed that the compounds interfered with viral adsorption, exhibited virucidal effects, and inhibited multiple stages of the replication cycle. Docking studies confirmed strong binding to key viral enzymes, supported by HOMO (half-maximal effective concentration) - LUMO (lowest unoccupied molecular orbital) analysis.
These findings highlight organochalcogen compounds as promising dual-action antiviral candidates with broad-spectrum activity against ZIKV and CHIKV. Further preclinical investigations are warranted to explore their therapeutic potential.
寨卡病毒（ZIKV）和基孔肯雅病毒（CHIKV）等新兴虫媒病毒仍然是重大的公共卫生威胁。本研究旨在评估六种有机硫属元素化合物对ZIKV和CHIKV的抗病毒潜力。
在Vero细胞中评估化合物的细胞毒性和抗病毒活性。使用蚀斑减少试验、添加时间研究、病毒吸附试验和杀病毒试验确定抗病毒效果。进行分子对接和密度泛函理论（DFT）计算以研究与病毒靶点的相互作用和电子性质。
化合物 、 、 和 表现出强效抗病毒活性且细胞毒性低，在微摩尔范围内的半数最大有效浓度（EC₅₀）值证明对病毒复制有有效抑制作用，且具有良好的选择性指数。机制分析表明这些化合物干扰病毒吸附，表现出杀病毒作用，并抑制复制周期的多个阶段。对接研究证实与关键病毒酶有强结合，最高占据分子轨道（HOMO）-最低未占据分子轨道（LUMO）分析支持这一结果。
这些发现突出了有机硫属元素化合物作为有前景的双作用抗病毒候选物，对ZIKV和CHIKV具有广谱活性。有必要进行进一步的临床前研究以探索它们的治疗潜力。
