Peptide fusion inhibitors targeting the HIV-1 gp41: a patent review (2009 - 2014).

INTRODUCTION: As the first peptide HIV fusion inhibitor targeting gp41, enfuvirtide (T20) was approved by the US FDA in 2003 as a salvage therapy for HIV/AIDS patients who failed to respond to the then existing antiretroviral therapeutics. However, its clinical application is limited by its relatively low potency, low genetic barrier to drug resistance and short half-life. Therefore, it is essential to develop new peptide HIV fusion inhibitors with improved antiviral efficacy, drug-resistance profile and pharmaceutical properties.

AREAS COVERED: In this paper, we reviewed the patents, patent applications and related research articles for the development of new peptide fusion inhibitors targeting the HIV-1 gp41 published between 2009 and 2014.

EXPERT OPINION: To improve enfuvirtide's anti-HIV efficacy, drug-resistance profile, half-life and pharmaceutical properties, the best approaches include the addition of the pocket-binding domain (PBD) to the N-terminus of T20 and linking of the M-T hook to the N-terminus of PBD, as well as conjugation of cholesterol, serum albumin-binding motif or gp120-binding fragment with a PBD-containing C-terminal heptad repeat-peptide. Therefore, sifuvirtide from Tianjin FusoGen Pharmaceuticals, Inc., albuvirtide from Frontier Biotechnologies Co., Ltd., cholesterol-conjugated HIV fusion inhibitor from the Institute of Pathogen Biology, Chinese Academy of Medical Science, 2DLT, a bivalent HIV fusion inhibitor/inactivator, and an enfuvirtide/sifuvirtide combination regimen from the New York Blood Center may all have potential as next-generation HIV fusion inhibitors targeting gp41 for clinical use.