Abstract
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.
Highlights
Acquired immune deficiency syndrome (AIDS) is one of the major diseases of large public health impact
CD4 is critical in the process of Human immunodeficiency virus type 1 (HIV-1) invasion into its host cells, and blocking the interaction of
CD4 is critical in the process of HIV-1 invasion into its host cells, and blocking the interaction of CD4 and gp120 can significantly inhibit HIV-1 entry into host cells [52]
Summary
Acquired immune deficiency syndrome (AIDS) is one of the major diseases of large public health impact. It is caused by HIV, and it represents the final stage of HIV infection [1]. One of the hallmarks of HIV infection is the selective destruction of CD4 T-cells [2]. HIV is usually antiretroviral therapy (ART), with double or triple drug combinations chosen from approved drugs [3,4]. The viral entry process is one of the most promising targets for the development of new anti-HIV drugs effective in the virus replication cycle for the long-term treatment of patients with AIDS [5,6]. Two types of HIV are recognized, HIV-1, which is responsible for the majority of HIV infections worldwide, and HIV type 2 (HIV-2), which causes the infection endemic in western
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