Virtual Screening, Biological Evaluation, and 3D-QSAR Studies of New HIV-1 Entry Inhibitors That Function via the CD4 Primary Receptor
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 dis...
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| Format: | Article |
| Language: | English |
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MDPI AG
2018-11-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/23/11/3036 |
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| author | Chaozai Zhang Huijun Zhang Lina S. Huang Siyu Zhu Yan Xu Xing-Quan Zhang Robert T. Schooley Xiaohong Yang Ziwei Huang Jing An |
| author_facet | Chaozai Zhang Huijun Zhang Lina S. Huang Siyu Zhu Yan Xu Xing-Quan Zhang Robert T. Schooley Xiaohong Yang Ziwei Huang Jing An |
| author_sort | Chaozai Zhang |
| collection | DOAJ |
| description | 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 <b>3</b> 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. |
| first_indexed | 2024-12-10T08:49:17Z |
| format | Article |
| id | doaj.art-4a308607a0484dd99f97f747e28c3c93 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-10T08:49:17Z |
| publishDate | 2018-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-4a308607a0484dd99f97f747e28c3c932022-12-22T01:55:38ZengMDPI AGMolecules1420-30492018-11-012311303610.3390/molecules23113036molecules23113036Virtual Screening, Biological Evaluation, and 3D-QSAR Studies of New HIV-1 Entry Inhibitors That Function via the CD4 Primary ReceptorChaozai Zhang0Huijun Zhang1Lina S. Huang2Siyu Zhu3Yan Xu4Xing-Quan Zhang5Robert T. Schooley6Xiaohong Yang7Ziwei Huang8Jing An9Department of Medicine, Division of Infectious Diseases, School of Medicine, University of California San Diego, La Jolla, CA 92037, USADepartment of Medicine, Division of Infectious Diseases, School of Medicine, University of California San Diego, La Jolla, CA 92037, USADepartment of Medicine, Division of Infectious Diseases, School of Medicine, University of California San Diego, La Jolla, CA 92037, USADepartment of Medicine, Division of Infectious Diseases, School of Medicine, University of California San Diego, La Jolla, CA 92037, USASchool of Life Sciences, Tsinghua University, Beijing 100084, ChinaDepartment of Medicine, Division of Infectious Diseases, School of Medicine, University of California San Diego, La Jolla, CA 92037, USADepartment of Medicine, Division of Infectious Diseases, School of Medicine, University of California San Diego, La Jolla, CA 92037, USASchool of Pharmaceutical Sciences, Jilin University, Changchun 130021, ChinaDepartment of Medicine, Division of Infectious Diseases, School of Medicine, University of California San Diego, La Jolla, CA 92037, USADepartment of Medicine, Division of Infectious Diseases, School of Medicine, University of California San Diego, La Jolla, CA 92037, USAHuman 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 <b>3</b> 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.https://www.mdpi.com/1420-3049/23/11/3036HIV-1entry inhibitorCD4virtual screening3D-QSAR |
| spellingShingle | Chaozai Zhang Huijun Zhang Lina S. Huang Siyu Zhu Yan Xu Xing-Quan Zhang Robert T. Schooley Xiaohong Yang Ziwei Huang Jing An Virtual Screening, Biological Evaluation, and 3D-QSAR Studies of New HIV-1 Entry Inhibitors That Function via the CD4 Primary Receptor Molecules HIV-1 entry inhibitor CD4 virtual screening 3D-QSAR |
| title | Virtual Screening, Biological Evaluation, and 3D-QSAR Studies of New HIV-1 Entry Inhibitors That Function via the CD4 Primary Receptor |
| title_full | Virtual Screening, Biological Evaluation, and 3D-QSAR Studies of New HIV-1 Entry Inhibitors That Function via the CD4 Primary Receptor |
| title_fullStr | Virtual Screening, Biological Evaluation, and 3D-QSAR Studies of New HIV-1 Entry Inhibitors That Function via the CD4 Primary Receptor |
| title_full_unstemmed | Virtual Screening, Biological Evaluation, and 3D-QSAR Studies of New HIV-1 Entry Inhibitors That Function via the CD4 Primary Receptor |
| title_short | Virtual Screening, Biological Evaluation, and 3D-QSAR Studies of New HIV-1 Entry Inhibitors That Function via the CD4 Primary Receptor |
| title_sort | virtual screening biological evaluation and 3d qsar studies of new hiv 1 entry inhibitors that function via the cd4 primary receptor |
| topic | HIV-1 entry inhibitor CD4 virtual screening 3D-QSAR |
| url | https://www.mdpi.com/1420-3049/23/11/3036 |
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