Peptide HIV fusion inhibitors: modifications and conjugations

Abstract

HIV fusion inhibitors are a group of virus entry preventing drugs aimed at membrane fusion. Several peptide drugs are screened with potent capacity to block virus-host cell fusion efficiently, and researchers have begun to focus on peptide drug design. However, so far T-20 is the only fusion inhibitor that has been approved by the FDA and utilised in treating therapy-experienced AIDS patients. The application of conventional peptide drugs is often limited by their short in vivo half-life and heavy dose subcutaneous injection. Thus, it is necessary to design new types of peptides or alter the existing peptides in a modified form to reach lower EC₅₀ values and obtain longer in vivo half-lives. Here, we summarise the inhibitory mechanisms of peptide fusion inhibitors designed with anti-HIV potency. Also, we further discuss the recent achievement in these peptide derivatives. Several approaches have been applied to optimise the peptide properties, and we provide examples of successful peptide conjugation strategies to provide hints for additional peptide therapeutic design.