Antiviral programs

HIV
Since its emergence in 1981 HIV-related epidemic has taken over 25 million of lives worldwide and prevalence rate continues to rise. Despite the availability of medications, most patients develop drug resistance upon prolonged treatment regiment. The high rate of viral mutagenesis leads to the production of new viral strains - irresponsive to the existing therapies. Proteologics approaches the problem from different perspective focusing on achieving a durable suppression of HIV replication. As opposed to the traditional inhibition of viral targets or viral-host interaction sites, we aim at blocking the host proteins directly associated with viral spreading. This novel generation of antivirals is expected to raise the barrier of drug resistance, forcing the deleterious transmission rate to decrease.

HIV & Ubiquitin
Groundbreaking discoveries published in 2001 in the Proceedings of the National Academy of Sciences (USA) indicate the direct involvement of ubiquitin-proteosome pathway in the late stages of the HIV life cycle. Studies have shown that blockade of proteosomal system in HIV-infected CD4+ immune cells results in deficiency of both viral budding (escape from cell surface) and viral maturation, making the virus less susceptible to infecting other cells. Although effective, non-specific blockade of proteosomal function raises multiple concerns stemming from interference with normal cellular processes. Proteologics has addressed the issue and since identified a number of specific E3 ligases critical to the late stages of the HIV and other viruses' life cycles. Specific targeting of ubiquitin-proteosome cascade is expected to alleviate the associated toxicity, representing an exciting potential for next generation of antiviral drugs.

Proteologics propels two anti-HIV programs rapidly expanding the knowledge of ubiquitin-based virology. We have identified two specific E3 ligase targets important for the survival of HIV and other enveloped viruses. The first target is hPOSH, a RING-finger ubiqtuitin ligase known to modulate a newly discovered host mechanism essential to a late stage in the virus life cycle. The active search for hPOSH inhibitors is in progress and the resulting compounds are expected to be much more effective against the emergence of new viral resistance than currently existing therapies.
Proteologics' second HIV drug discovery program shows similar promise, representing a multi-pronged attack on HIV through a completely novel class of drugs, each of them acting on newly discovered, distinct, intervention points.

Other viruses
Initial results in other viruses show that hPOSH-inhibitor-based drug may be effective against a broad range of other clinically important viruses. This raises the prospect of a first true broad spectrum anti viral drug against enveloped viruses. Proteologics plans include assessing the potency of compounds against many additional virus types.

CANCER PROGRAMS - collaboration
Proteologics entered R&D collaboration with Teva Pharmaceutical Industries Ltd. to promote two anti-cancer projects. The projects follow different directions: the discovery and validation of a novel E3 ligase target; and identification of E3 ligase critical for the proteosomal degradation of a known chemotherapy target. Proudly, we have reached the deadlines in record times in both projects - far preceding the scheduled timeframe. In addition to Teva, we have also formed collaborations with several international academic institutions like the City of Hope Research Hospital in California, US and the Erlangen University in Germany