Gladysheva Anastasia, Osinkina Irina, Radchenko Nikita, Alkhireenko Daria, Agafonov Alexander
State Research Center of Virology and Biotechnology "Vector", 630559 Kol'tsovo, Russia.
Natural Sciences Department, Novosibirsk State University, 630090 Novosibirsk, Russia.
Int J Mol Sci. 2024 Dec 20;25(24):13654. doi: 10.3390/ijms252413654.
Currently, a large number of novel tick-borne viruses potentially pathogenic to humans are discovered. Studying many of them by classical methods of virology is difficult due to the absence of live viral particles or a sufficient amount of their genetic material. In this case, the use of modern methods of bioinformatics and synthetic and structural biology can help. Haseki tick virus (HSTV) is a recently discovered tick-borne unclassified ssRNA(+) virus. HSTV-positive patients experienced fever and an elevated temperature. However, at the moment, there is no information on the tertiary structure and functions of its proteins. In this work, we used AlphaFold 3 and other bioinformatic tools for the annotation of HSTV nonstructural proteins, based on the principle that the tertiary structure of a protein is inextricably linked with its molecular function. We were the first to obtain models of tertiary structures and describe the putative functions of HSTV nonstructural proteins (NS3 helicase, NS3 protease, NS5 RNA-dependent RNA-polymerase, and NS5 methyltransferase), which play a key role in viral genome replication. Our results may help in further taxonomic identification of HSTV and the development of direct-acting antiviral drugs, POC tests, and vaccines.
目前，发现了大量可能对人类致病的新型蜱传病毒。由于缺乏活病毒颗粒或其足够数量的遗传物质，利用传统病毒学方法对其中许多病毒进行研究存在困难。在这种情况下，使用现代生物信息学以及合成生物学和结构生物学方法会有所帮助。哈塞基蜱病毒（HSTV）是最近发现的一种蜱传未分类单链RNA（+）病毒。HSTV阳性患者出现发热和体温升高症状。然而，目前尚无关于其蛋白质三级结构和功能的信息。在这项工作中，我们基于蛋白质三级结构与其分子功能紧密相关的原理，使用AlphaFold 3和其他生物信息学工具对HSTV非结构蛋白进行注释。我们首次获得了三级结构模型，并描述了HSTV非结构蛋白（NS3解旋酶、NS3蛋白酶、NS5 RNA依赖性RNA聚合酶和NS5甲基转移酶）的假定功能，这些蛋白在病毒基因组复制中起关键作用。我们的结果可能有助于HSTV的进一步分类鉴定以及直接作用抗病毒药物、即时检验和疫苗的研发。
