Department of Medicine, Division of Infectious Diseases, School of Medicine, University of California San Diego, La Jolla, CA 92037, USA.
School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China.
Molecules. 2018 Nov 20;23(11):3036. doi: 10.3390/molecules23113036.
Human immunodeficiency virus type 1 (HIV-1) is responsible for the majority of HIV infections worldwide, and we still lack a cure for this infection. Blocking the interaction of HIV-1 and its primary receptor CD4 is one strategy for identifying new anti-HIV-1 entry inhibitors. Here we report the discovery of a novel ligand that can inhibit HIV-1 entry and infection via CD4. Biological and computational analyses of this inhibitor and its analogs, using bioactivity evaluation, Rule of Five (RO5), comparative molecular field analysis (CoMFA)/comparative molecular similarity index analysis (CoMSIA) models, and three-dimensional quantitative structure-activity relationship (3D-QSAR), singled out compound as a promising lead molecule for the further development of therapeutics targeting HIV-1 entry. Our study demonstrates an effective approach for employing structure-based, rational drug design techniques to identify novel antiviral compounds with interesting biological activities.
人类免疫缺陷病毒 1 型（HIV-1）是导致全球大多数 HIV 感染的原因，而我们仍然缺乏对此感染的治愈方法。阻断 HIV-1 与其主要受体 CD4 的相互作用是识别新的抗 HIV-1 进入抑制剂的一种策略。在这里，我们报告了一种新型配体的发现，该配体可以通过 CD4 抑制 HIV-1 的进入和感染。使用生物活性评估、五规则（RO5）、比较分子场分析（CoMFA）/比较分子相似性指数分析（CoMSIA）模型和三维定量构效关系（3D-QSAR）对该抑制剂及其类似物进行的生物学和计算分析，确定化合物 为针对 HIV-1 进入的治疗进一步开发有前途的先导分子。我们的研究证明了一种有效的方法，可用于采用基于结构的合理药物设计技术来识别具有有趣生物学活性的新型抗病毒化合物。
