Recombinant HIV type 1 Glycoprotein 41 Protein (a.a. 542-764) [BGAL]

Purpose of review We summarize the latest research on the progress to understand the neutralizing epitopes present within the membrane proximal external region (MPER) of the HIV-1 fusion protein subunit gp41. Recent findings The HIV-1 fusion protein subunit gp41 contains a highly conserved sequence that is essential for membrane fusion and targeted by broadly neutralizing antibodies such as 2F5, 4E10, Z13e1, and 10E8. These antibodies recognize a linear gp41 epitope with high affinity, but require additional hydrophobic sequences present in their heavy chain CDR3 for neutralization. Recent structural studies on mAbs 4E10 and 10E8 provide molecular details for specific interactions with lipids and implicate part of the transmembrane region as the relevant 10E8 epitope. Although many different approaches have been applied to engineer gp41 immunogens that can induce broadly neutralizing antibodies directed toward MPER, only modest success has yet been reported. Summary The new structural details on the complex gp41-lipidic epitope will spur new approaches to design gp41MPER immunogens that might induce broadly neutralizing antibody responses.

Class I enveloped viruses share similarities in their apparent use of a hexameric coiled-coil assembly to drive the merging of virus and host cell membranes. Inhibition of coiled coil-mediated interactions using bioactive peptides that replicate an alpha-helical chain from the viral fusion machinery has significant antiviral potential. Here, we present the construction of a series of lipopeptides composed of a de novo heptad repeat sequence-based alpha-helical peptide plus a hydrocarbon tail. Promisingly, the constructs adopted stable alpha-helical conformations and exhibited relatively broad-spectrum antiviral activities against Middle East respiratory syndrome coronavirus (MERS-CoV) and influenza A viruses (IAVs). Together, these findings reveal a new strategy for relatively broad-spectrum antiviral drug discovery by relying on the tunability of the alpha-helical coiled-coil domains present in all class I fusion proteins and the amphiphilic nature of the individual helices from this multihelix motif.