Mishra Bibhudutta, Raghuraman Raaghavi, Agarwal Arjun, Aduri Raviprasad
1Department of Biological Sciences, Birla Institute of Technology and Science, Pilani, K K Birla Goa Campus, Zuarinagar, South Goa, Goa 403 726 India.
2Department of Computer Science and Information Systems, Birla Institute of Technology and Science, Pilani, K K Birla Goa Campus, Zuarinagar, South Goa, Goa 403 726 India.
Virusdisease. 2019 Dec;30(4):477-489. doi: 10.1007/s13337-019-00561-2. Epub 2019 Dec 11.
Dengue virus (DENV) is a mosquito-borne flavivirus which causes Dengue fever and severe Dengue. It exists as four antigenically different serotypes that are further classified into genotypes with varying degrees of pathogenicity. The non-structural protein 1 (NS1) of DENV has an important role in viral replication and its pathogenesis. NS1 is also considered as an important diagnostic marker for Dengue pathogenesis. To the best of our knowledge, there are no attempts to explore small molecule drugs to target the NS1 of all the serotypes. Here, we have taken the DENV 2 NS1 crystal structure as a reference to model the NS1 structure of the other three serotypes. Once the active site of the NS1 is identified, virtual screening of plant flavonoids is carried out against the NS1 of all the four serotypes. The top 200 molecules in the library with high binding affinities are further analysed to find the common ones having comparable affinities to all the four serotypes. The predicted common flavonoids are subjected to ADMET profiling to further select the most potential molecules that can be used to target NS1 of all the four serotypes.
登革病毒（DENV）是一种由蚊子传播的黄病毒，可引起登革热和重症登革热。它以四种抗原性不同的血清型存在，这些血清型进一步分为具有不同致病程度的基因型。登革病毒的非结构蛋白1（NS1）在病毒复制及其发病机制中起重要作用。NS1也被认为是登革热发病机制的重要诊断标志物。据我们所知，尚未有人尝试探索针对所有血清型NS1的小分子药物。在此，我们以登革病毒2型NS1晶体结构为参考，对其他三种血清型的NS1结构进行建模。一旦确定了NS1的活性位点，就针对所有四种血清型的NS1进行植物黄酮类化合物的虚拟筛选。对文库中具有高结合亲和力的前200个分子进行进一步分析，以找到对所有四种血清型具有相当亲和力的共同分子。对预测的共同黄酮类化合物进行ADMET分析，以进一步选择可用于靶向所有四种血清型NS1的最具潜力的分子。
