Virtual Screening, Biological Evaluation, and 3D-QSAR Studies of New HIV-1 Entry Inhibitors That Function via the CD4 Primary Receptor.

Zhang, Chaozai; Zhang, Huijun; Huang, Lina S.; Zhu, Siyu; Xu, Yan; Zhang, Xing-Quan; Schooley, Robert T.; Yang, Xiaohong; Huang, Ziwei; An, Jing; Brogi, Simone

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 3 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.

HIV infections; LIGANDS (Biochemistry); DRUG design; MOLECULES; BIOMOLECULES

Molecules, 2018, Vol 23, Issue 11, p3036

1420-3049

Academic Journal

10.3390/molecules23113036