Tick-borne encephalitis virus (TBEV) is a medically important representative of the Flaviviridae family. The TBEV genome encodes a single polyprotein, which is co/post-translationally cleaved into three structural and seven non-structural proteins. Of the non-structural proteins, NS5, contains an RNA-dependent RNA polymerase (RdRp) domain that is highly conserved and is responsible for the genome replication. Screening for potential antivirals was done using a hybrid receptor and ligand-based pharmacophore search likely targeting the RdRp domain. For the identification of pharmacophores, a mixture of small probe molecules and nucleotide triphosphates were used. The ligand/receptor interaction screenings of structures from the ZINC database resulted in five compounds. Zinc 3677 and 7151 exhibited lower cytotoxicity and were tested for their antiviral effect against TBEV in vitro. Zinc 3677 inhibited TBEV at micromolar concentrations. The results indicate that Zinc 3677 represents a good target for structure-activity optimizations leading potentially to a discovery of effective TBEV antivirals.

ick传脑炎病毒（TBEV）是黄病毒科的重要医学代表家庭。TBEV基因组编码单个多蛋白，该蛋白被共/翻译后切割成三个结构蛋白和七个非结构蛋白。在非结构蛋白中，NS5包含一个高度保守的RNA依赖性RNA聚合酶（RdRp）结构域，负责基因组复制。使用可能靶向RdRp结构域的杂合受体和基于配体的药效团搜索来进行潜在抗病毒药物的筛选。为了鉴定药效团，使用了小探针分子和三磷酸核苷酸的混合物。从ZINC数据库进行的结构的配体/受体相互作用筛选产生了5种化合物。锌3677和7151表现出较低的细胞毒性，并在体外测试了其对TBEV的抗病毒作用。锌3677以微摩尔浓度抑制TBEV。结果表明，锌3677代表了结构活性优化的良好靶标，可能导致发现有效的TBEV抗病毒剂。