Smorodintsev Research Institute of Influenza, Professora Popova str, 15/17, 197376 St. Petersburg, Russia.
Vorozhtsov Novosibirsk Institute of Organic Chemistry, Acad. Lavrentyev av. 9, 630090 Novosibirsk, Russia.
Int J Mol Sci. 2023 Aug 18;24(16):12933. doi: 10.3390/ijms241612933.
Respiratory syncytial virus (RSV) is known to cause annual epidemics of respiratory infections; however, the lack of specific treatment options for this disease poses a challenge. In light of this, there has been a concerted effort to identify small molecules that can effectively combat RSV. This article focuses on the mechanism of action of compound K142, which was identified as a primary screening leader in the earlier stages of the project. The research conducted demonstrates that K142 significantly reduces the intensity of virus penetration into the cells, as well as the formation of syncytia from infected cells. These findings show that the compound's interaction with the surface proteins of RSV is a key factor in its antiviral activity. Furthermore, pharmacological modeling supports that K142 effectively interacts with the F-protein. However, in vivo studies have shown only weak antiviral activity against RSV infection, with a slight decrease in viral load observed in lung tissues. As a result, there is a need to enhance the bioavailability or antiviral properties of this compound. Based on these findings, we hypothesize that further modifications of the compound under study could potentially increase its antiviral activity.
呼吸道合胞病毒(RSV)已知会导致呼吸道感染的年度流行;然而,针对这种疾病缺乏特定的治疗选择是一个挑战。鉴于此,人们一直在努力寻找可以有效对抗 RSV 的小分子。本文重点介绍了化合物 K142 的作用机制,该化合物在项目早期的初步筛选中被确定为主要筛选先导物。研究表明,K142 显著降低了病毒穿透细胞的强度,以及感染细胞形成合胞体的强度。这些发现表明,该化合物与 RSV 表面蛋白的相互作用是其抗病毒活性的关键因素。此外,药理学模型支持 K142 与 F 蛋白有效相互作用。然而,体内研究表明,该化合物对 RSV 感染仅有微弱的抗病毒活性,在肺组织中观察到病毒载量略有下降。因此,需要提高该化合物的生物利用度或抗病毒特性。基于这些发现,我们假设进一步修饰研究中的化合物可能会提高其抗病毒活性。