Integrative Structural Biology Laboratory, National Institute of Immunology, New Delhi, India.
PLoS One. 2024 Oct 25;19(10):e0311548. doi: 10.1371/journal.pone.0311548. eCollection 2024.
Dengue viral infection is caused by the Dengue virus, which spreads to humans through the bite of infected mosquitos. Dengue affects over half of the global population, with an estimated 500 million infections per year. Despite this, no effective treatment is currently available, however, several promising candidates are undergoing pre-clinical/clinical testing. The existence of four major serotypes is an important challenge in the development of drugs and vaccines to combat Dengue virus infection. Hence, the drug/vaccine thereby developed should neutralize all the four serotypes equally. However, there is no pan-serotype specific treatment for Dengue virus, thereby emphasizing the need for the identification of novel drug-like compounds that can target all serotypes of the Dengue virus equally. To this end, we employed virtual screening methodologies to find drug-like compounds that target the domain III of glycoprotein E. Most importantly, domain III of E protein is involved in viral fusion with the host membrane and is also targeted by neutralizing antibodies. Our study found two small molecule drug-like compounds (out of the 3 million compounds screened) having similar binding affinity with all four serotypes. The compounds thereby identified exhibit favourable drug like properties and can be developed as a treatment for Dengue virus.
登革热病毒感染是由登革病毒引起的，这种病毒通过受感染的蚊子叮咬传播给人类。登革热影响了全球一半以上的人口，估计每年有 5 亿人感染。尽管如此，目前还没有有效的治疗方法，但是有几个有前途的候选药物正在进行临床前/临床试验。四种主要血清型的存在是开发药物和疫苗来对抗登革热病毒感染的一个重要挑战。因此，开发的药物/疫苗应该能平等中和所有四种血清型。然而，目前还没有针对登革热病毒的泛血清型特异性治疗方法，因此需要确定能够平等针对登革热病毒所有血清型的新型类药化合物。为此，我们采用虚拟筛选方法来寻找针对糖蛋白 E 结构域 III 的类药化合物。最重要的是，E 蛋白的结构域 III 参与病毒与宿主膜的融合，也是中和抗体的靶标。我们的研究发现了两种小分子类药化合物（在筛选的 300 万种化合物中），它们与所有四种血清型都具有相似的结合亲和力。因此鉴定出的化合物具有良好的类药特性，可以开发为登革热病毒的治疗方法。
