García-Ariza Leidy L, Rocha-Roa Cristian, Padilla-Sanabria Leonardo, Castaño-Osorio Jhon C
Grupo de Inmunología Molecular, Centro de Investigaciones Biomédicas, Universidad del Quindío, Armenia, Colombia.
Grupo de Parasitología Molecular, Centro de Investigaciones Biomédicas, Universidad del Quindío, Armenia, Colombia.
Front Chem. 2022 Feb 10;10:637266. doi: 10.3389/fchem.2022.637266. eCollection 2022.
Dengue virus (DENV) is the causative agent of dengue fever. Annually, there are about 400 million new cases of dengue worldwide, and so far there is no specific treatment against this disease. The NS5 protein is the largest and most conserved viral protein among flaviviruses and is considered a therapeutic target of great interest. This study aims to search drug-like compounds for possible inhibitors of the NS5 protein in the four serotypes of DENV. Using a virtual screening from a ∼642,759-compound database, we suggest 18 compounds with NS5 binding and highlight the best compound per region, in the methyltransferase and RNA-dependent RNA polymerase domains. These compounds interact mainly with the amino acids of the catalytic sites and/or are involved in processes of protein activity. The identified compounds presented physicochemical and pharmacological properties of interest for their use as possible drugs; furthermore, we found that some of these compounds do not affect cell viability in Huh-7; therefore, we suggest evaluating these compounds as candidates in future research.
登革病毒（DENV）是登革热的病原体。全球每年约有4亿例登革热新发病例，迄今为止，尚无针对该疾病的特效治疗方法。NS5蛋白是黄病毒中最大且最保守的病毒蛋白，被认为是极具研究价值的治疗靶点。本研究旨在从登革病毒四种血清型中寻找可能作为NS5蛋白抑制剂的类药物化合物。通过对一个约642,759种化合物的数据库进行虚拟筛选，我们提出了18种与NS5结合的化合物，并突出了甲基转移酶和RNA依赖性RNA聚合酶结构域中每个区域的最佳化合物。这些化合物主要与催化位点的氨基酸相互作用和/或参与蛋白质活性过程。所鉴定的化合物具有作为潜在药物的理化和药理特性；此外，我们发现其中一些化合物对Huh-7细胞活力没有影响；因此，我们建议在未来的研究中将这些化合物作为候选药物进行评估。
