Strategies and Progress in CXCR4-Targeted Anti-Human Immunodeficiency Virus (HIV) Therapeutic Development

The acquired immunodeficiency syndrome (AIDS), caused by the human immunodeficiency virus (HIV), has been a global public health challenge for several decades. The majority of HIV infection is caused by the human immunodeficiency virus type 1 (HIV-1), which enters and infects a host cell via the cell surface proteins of CD4 as the primary receptor, and chemokine receptors CXCR4 or CCR5 as the coreceptor-then undergoing replication using the cell's intracellular machinery. Whereas many drugs targeting CCR5-mediated entry or HIV-1 replication via reverse transcriptase or proteases have long been used clinically, agents targeting CXCR4 are yet to be advanced to clinical application. Here in this review we highlight some of the strategies for and progress made in the discovery of novel small molecules, peptides, and larger molecules that target CXCR4, and their future prospects for translation into the clinic as a new class of anti-HIV therapeutics.

Automated summary

AIDS caused by HIV-1 has been a global public health challenge for decades. While drugs targeting CCR5-mediated entry or HIV-1 replication have been used clinically, drugs targeting CXCR4 have not yet reached clinical application. Research is ongoing on discovering novel molecules targeting CXCR4 for potential future anti-HIV therapeutic development.