Sphingolipid-peptide conjugates with potent anti-viral activity.
According to the WHO, 34 million people around the world are afflicted with HIV, the causative agent of AIDS, with approximately 2.5 million new infections diagnosed each year. The development of new drugs against HIV has been the focus of intense research since its discovery. The market size of HIV-1 treatment is indeed significant with drug sales expected to rise from $13.3 bn in 2011 to $16.7 bn in 2020 in the Western world alone. Nevertheless, there is a highly unmet need for innovative HIV treatment approaches. One such approach is the design of early entry inhibitors that are able to block viral fusion and entry into the host cell. The present technology presents sphingolipid-peptide conjugates (sphingo-peptides) with a potent capacity to interfere with HIV viral fusion.
The first step in the life cycle of enveloped viruses such as the HIV-1 is entry into their host cells by membrane fusion. Therefore, the dynamic process of HIV fusion and entry
represents a valid target for rational drug design. A team of researchers at the Weizmann Institute has developed unique sphingolipid-peptide (short peptides less 17 amino acids) conjugates that block the fusion of the HIV virus to its host cell membrane. Remarkably, the sphingolipid moiety endowed potent anti-viral activity to otherwise poorly and nonactive peptides. The peptide sequence is based on the reserved core of the virus therefore, not likely to accumulate mutations. Moreover, the sphingo-peptide inhibitors were shown to be highly effective against both wt as well as drug-resistant HIV strains.