Tertiary Structures of Haseki Tick Virus Nonstructural Proteins Are Similar to Those of Orthoflaviviruses

A large number of novel viruses potentially pathogenic for humans are discovered currently. Studying many of them by classical methods of virology is difficult due to the absence of a live viral particles or a sufficient amount of its genetic material. In this case, the use of modern methods of bioinformatics, 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 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 for annotation of HSTV protein functions, 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). These proteins play a key role in the replication of the viral genome and can be targets for the development of direct-acting antiviral drugs.