Ferla Salvatore, Manganaro Roberto, Benato Sara, Paulissen Jasmine, Neyts Johan, Jochmans Dirk, Brancale Andrea, Bassetto Marcella
Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff, King Edward VII Avenue, Cardiff CF103NB, UK.
Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff, King Edward VII Avenue, Cardiff CF103NB, UK.
Bioorg Med Chem. 2020 Apr 15;28(8):115401. doi: 10.1016/j.bmc.2020.115401. Epub 2020 Feb 26.
Respiratory syncytial virus (RSV) is the main cause of lower respiratory tract diseases in infants and young children, with potentially serious and fatal consequences associated with severe infections. Despite extensive research efforts invested in the identification of therapeutic measures, no vaccine is currently available, while treatment options are limited to ribavirin and palivizumab, which both present significant limitations. While clinical and pre-clinical candidates mainly target the viral fusion protein, the nucleocapsid protein or the viral polymerase, our focus has been the identification of new antiviral compounds targeting the viral M2-1 protein, thanks to the presence of a zinc-ejecting group in their chemical structure. Starting from an anti-RSV hit we had previously identified with an in silico structure-based approach, we have designed, synthesised and evaluated a new series of dithiocarbamate analogues, with which we have explored the antiviral activity of this scaffold. The findings presented in this work may provide the basis for the identification of a new antiviral lead to treat RSV infections.
呼吸道合胞病毒（RSV）是婴幼儿下呼吸道疾病的主要病因，严重感染可能导致严重且致命的后果。尽管在确定治疗措施方面投入了大量研究工作，但目前尚无可用疫苗，治疗选择仅限于利巴韦林和帕利珠单抗，而这两种药物都存在明显局限性。虽然临床和临床前候选药物主要针对病毒融合蛋白、核衣壳蛋白或病毒聚合酶，但由于其化学结构中存在锌排出基团，我们的重点一直是鉴定针对病毒M2-1蛋白的新型抗病毒化合物。从我们之前通过基于计算机模拟结构的方法鉴定出的一种抗RSV活性分子出发，我们设计、合成并评估了一系列新的二硫代氨基甲酸盐类似物，并借此探索了该支架的抗病毒活性。这项工作中呈现的研究结果可能为鉴定用于治疗RSV感染的新型抗病毒先导药物提供依据。
