Opening the HIV envelope: potential of CD4 mimics as multifunctional HIV entry inhibitors.

Annemarie Laumaea, Amos B Smith, Joseph Sodroski, Andrés Finzi

Current opinion in HIV and AIDS 2020 Sep

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Close to 2 million individuals globally become infected with HIV-1 each year and just over two-thirds will have access to life-prolonging antivirals. However, the rapid development of drug resistance creates challenges, such that generation of more effective therapies is not only warranted but a necessary endeavour. This review discusses a group of HIV-1 entry inhibitors known as CD4 mimics which exploit the highly conserved relationship between the HIV-1 envelope glycoprotein and the receptor, CD4. We review the structure/function guided evolution of these inhibitors, vital mechanistic insights that underpin broad and potent functional antagonism, recent evidence of utility demonstrated in animal and physiologically relevant in-vitro models, and current progress towards effective new-generation inhibitors. The current review highlights the promising potential of CD4 mimetics as multifunctional therapeutics.

Citation

Annemarie Laumaea, Amos B Smith, Joseph Sodroski, Andrés Finzi. Opening the HIV envelope: potential of CD4 mimics as multifunctional HIV entry inhibitors. Current opinion in HIV and AIDS. 2020 Sep;15(5):300-308