基于单萜取代的芳基香豆素的新型呼吸道合胞病毒（RSV）复制抑制剂。

Department of Medicinal Chemistry, N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Acad. Lavrentjev Ave. 9, 630090 Novosibirsk, Russia.

Laboratory of Chemotherapy for Viral Infections, Smorodintsev Research Intitute of Influenza, 197376 Saint-Petersburg, Russia.

Molecules. 2023 Mar 15;28(6):2673. doi: 10.3390/molecules28062673.

Respiratory syncytial virus (RSV) causes annual epidemics of respiratory infection. Usually harmless to adults, the RSV infection can be dangerous to children under 3 years of age and elderly people over 65 years of age, often causing serious problems, even death. At present, there are no vaccines and specific chemotherapeutic agents for the treatment of this disease, so the search for low-molecular weight compounds to combat RSV is a challenge. In this work, we have shown, for the first time, that monoterpene-substituted arylcoumarins are efficient RSV replication inhibitors at low micromolar concentrations. The most active compound has a selectivity index of about 200 and acts most effectively at the early stages of infection. The F protein of RSV is a potential target for these compounds, which is also confirmed by molecular docking and molecular dynamics simulation data.

呼吸道合胞病毒（RSV）会引起呼吸道感染的年度流行。通常对成年人无害，但 RSV 感染对 3 岁以下儿童和 65 岁以上老年人可能很危险，经常导致严重问题，甚至死亡。目前，尚无针对这种疾病的疫苗和特定化疗药物，因此寻找对抗 RSV 的低分子量化合物是一项挑战。在这项工作中，我们首次表明，单萜取代的芳基香豆素在低微摩尔浓度下是有效的 RSV 复制抑制剂。最活跃的化合物的选择性指数约为 200，并且在感染的早期阶段最有效。RSV 的 F 蛋白是这些化合物的潜在靶标，这也得到了分子对接和分子动力学模拟数据的证实。