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The Genesis and Future Prospects of Small Molecule HIV-1 Attachment Inhibitors

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Virus Entry Inhibitors

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1366))

Abstract

Gp120 is a critical viral proteins required for HIV-1 entry and infection. It facilitates HIV-1 binding to target cells, human-to-human transmission, relocation of virus from mucosa to lymph nodes, cell–cell infection and syncytium formation, and the bystander effect that kills uninfected CD4+ T-cells and other human cells. Molecules that bind to gp120 can inhibit its function by stabilizing conformations of the protein, leading to the inability to infect cells, and resulting in non-permissive. Small molecule-mediated stabilization of certain conformations of gp120 may also enhance recognition of HIV-1 infected cells by neutralizing antibodies and make the virus more susceptible to effector functions such as ADCC, which could potentially be part of future cure regimens. Additionally, HIV attachment inhibitors can complex with free gp120 and potentially repress both cytopathic effects from membrane-bound or soluble gp120. Fostemsavir (RukobiaTM), a phosphate prodrug of an HIV-1 attachment inhibitor that was recently approved for use in highly treatment experienced (HTE) patients with multidrug resistant HIV-1 is a first-in-class drug with a favorable safety profile that provides an additional treatment option for treatment in this population of patients with a high medical need.

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Authors and Affiliations

  1. Beijing Kawin Technology Share-Holding Co., Beijing, PR China

    Tao Wang

  2. ViiV Healthcare, Branford, CT, USA

    John F. Kadow & Mark Krystal

  3. Small Molecule Drug Discovery, Bristol-Myers Squibb Research and Development, Princeton, NJ, USA

    Nicholas A. Meanwell

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  1. Tao Wang
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  2. John F. Kadow
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  3. Nicholas A. Meanwell
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  4. Mark Krystal
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Correspondence to Tao Wang .

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Editors and Affiliations

  1. Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China

    Shibo Jiang

  2. Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China

    Lu Lu

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Wang, T., Kadow, J.F., Meanwell, N.A., Krystal, M. (2022). The Genesis and Future Prospects of Small Molecule HIV-1 Attachment Inhibitors. In: Jiang, S., Lu, L. (eds) Virus Entry Inhibitors. Advances in Experimental Medicine and Biology, vol 1366. Springer, Singapore. https://doi.org/10.1007/978-981-16-8702-0_4

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