HIV Entry and Its Inhibition by Bifunctional Antiviral Proteins

HIV entry is a highly specific and time-sensitive process that can be divided into receptor binding, coreceptor binding, and membrane fusion. Bifunctional antiviral proteins (bAVPs) exploit the multi-step nature of the HIV entry process by binding to two different extracellular targets. They are generated by expressing a fusion protein containing two entry inhibitors with a flexible linker. The resulting fusion proteins exhibit exceptional neutralization potency and broad cross-clade inhibition. In this review, we summarize the HIV entry process and provide an overview of the design, antiviral potency, and methods of delivery of bAVPs. Additionally, we discuss the advantages and limitations of bAVPs for HIV prevention and treatment.