Therapeutic potential of blocking HIV entry into cells: focus on membrane fusion inhibitors
- 1 August 1999
- journal article
- Published by Informa Healthcare in Expert Opinion on Investigational Drugs
- Vol. 8 (8) , 1157-1170
- https://doi.org/10.1517/13543784.8.8.1157
Abstract
Despite a number of recent therapeutic advancements, there remains an urgent need to develop a new class of therapy for human immunodeficiency virus (HIV). This review summarises attempts at blocking HIV binding and entry into host cells, an approach that would provide theoretical advantages over the currently available drugs targeting enzymes (reverse transcriptase and protease), brought into play in the later stages of the viral life cycle. The multi-step process of HIV entry into cells, binding of the surface glycoprotein (gp120) to the CD4 receptor and one of the chemokine receptors, followed by the membrane fusion step mediated by the transmembrane glycoprotein (gp41), has recently been understood with greater clarity. The importance of the chemokine co-receptors, such as CCR5 and CXCR4, for HIV entry may help to explain the limitations of earlier approaches using recombinant soluble CD4 or polyanionic compounds to interfere non-specifically with HIV glycoprotein function. Conversely, previous invest...Keywords
This publication has 54 references indexed in Scilit:
- Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibodyNature, 1998
- Recombinant Soluble CD4 Therapy in Patients with the Acquired Immunodeficiency Syndrome (AIDS) and AIDS-Related ComplexAnnals of Internal Medicine, 1990
- The Safety and Pharmacokinetics of Recombinant Soluble CD4 (rCD4) in Subjects with the Acquired Immunodeficiency Syndrome (AIDS) and AIDS-Related ComplexAnnals of Internal Medicine, 1990
- Synergistic Inhibition of Human Immunodeficiency Virus Type 1 (HIV-1) Replication In Vitro by Recombinant Soluble CD4 and 3'-Azido-3'-DeoxythymidineThe Journal of Infectious Diseases, 1989
- Mechanism of inhibitory effect of dextran sulfate and heparin on replication of human immunodeficiency virus in vitro.Proceedings of the National Academy of Sciences, 1988
- Dextran Sulfate Suppression of Viruses in the HIV Family: Inhibition of Virion Binding to CD4 + CellsScience, 1988
- A soluble CD4 protein selectively inhibits HIV replication and syncytium formationNature, 1988
- Soluble CD4 molecules neutralize human immunodeficiency virus type 1Nature, 1988
- soluble form of CD4 (T4) protein inhibits AIDS virus infectionNature, 1988
- HIV infection is blocked in vitro by recombinant soluble CD4Nature, 1988