Cell-based and biochemical screening approaches for the discovery of novel HIV-1 inhibitors

• Published in: Antiviral research Vol. 67; no. 3; pp. 121 - 140
• Main Authors: Westby, Mike, Nakayama, Grace R., Butler, Scott L., Blair, Wade S.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.09.2005; Elsevier
• Subjects: Anti-HIV Agents - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral screen; Biological and medical sciences; Drug discovery; Drug Evaluation, Preclinical - methods; HIV; HIV-1 - drug effects; Human immunodeficiency virus 1; Human viral diseases; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Medical sciences; Microbial Sensitivity Tests - methods; Novel inhibitors; Pharmacology. Drug treatments; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; PR; RT; RRE; SPA; HTS; Antiviral screen; TRF; FP; HR; CHO; LTR; Env; PEc; GFP; 7-TM GPCR; FRET; IC; EIA; Novel inhibitors; NRTI; HTRF; μARCS; IN; SEAP; NNRTI; CV-N; PIC; HOS; TC; beta-Gal; HIV; NC; CAT; ITC; PI; RNase H; FLIPR; NHEJ; Drug discovery; dsDNA; Ec; ELISA; Drug; Immunopathology; Antiretroviral agent; HIV-1 virus; Retroviridae; AIDS; Medical screening; Immune deficiency; Lentivirus; In vitro; Research and development; Infection; Virus; Screening; Viral disease; Antiviral; Inhibitor; Human immunodeficiency virus
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2005.06.006

The identification of novel HIV-1 inhibitors is facilitated by screening campaigns that combine the right screening strategy with a large diverse collection of drug-like compounds. Cell-based screening approaches offer some advantages in the quest for novel inhibitors because they can include multiple targets in a single screen and in some cases reveal targets and/or structures not captured in biochemical assays. However, follow-up activities for cell-based screens are often more complicated and resource intensive when compared to biochemical screens. Alternatively, biochemical screens usually offer the advantage of focusing on a single target with a well-defined set of follow-up assays. In this review we cover multiple cell-based and biochemical assay formats, many of which were designed to identify inhibitors that act through new mechanisms. Some of the assays discussed have been utilized in antiviral screens while others might be formatted for HTS or utilized as secondary assays in a screening campaign. As drug discovery efforts in the pharmaceutical industry shift away from traditional strategies, new approaches such as those presented here are likely to play a significant role in the identification of next generation HIV-1 inhibitors.