Technologies
PLANTIVIRALS™
Intrucept’s PLANTIVIRALS™ are novel, plant-derived antiviral proteins with exquisite potency against a broad spectrum of human pathogenic viruses, including HIV-1 and influenza viruses. One of our lead PLANTIVIRAL™ products, IBG-1, has shown the strongest HIV-1 inhibitory activity yet described for a biologic (eg. 25-times more potent than Fuzeon®). It shows potent neutralizing activity against a broad set of HIV-1 isolates from various clades. Similarly, another one of our lead PLANTIVIRAL™ products, IBG-3, exhibits activity against most influenza viruses tested, including the newly described avian flu virus [A H5N1], which could develop into a pandemic flu threat.
PLANTIVIRALS™ do not bind human serum proteins and have shown no cellular toxicity in vitro at concentrations greatly exceeding those required for therapeutic effect. This is significant because the ability to use therapeutic proteins in lower doses while maintaining efficacy could lead to higher safety margins (including lower potential immunogenicity), a lower cost of therapy, and thus the potential to penetrate markets more efficiently.
Native PLANTIVIRAL™ proteins were first isolated from marine plants in New Zealand and described by scientists at the National Cancer Institute, which holds patents on these molecules. Most evaluations of these proteins have been conducted with extracted materials. Intrucept has obtained commercial license rights from the NIH to selected PLANTIVIRALS™ made recombinantly using a patented manufacturing technology. The technology has already been used to produce active proteins in commercially relevant yields at a favorable projected cost of goods. Intrucept thus has freedom to operate and can develop and manufacture a new class of antiviral drugs with broad clinical utility and high commercial potential.
New Mode of Action of PLANTIVIRALS™
While medicinal chemistry has give rise to several categories of effective antimicrobial agents to control bacterial, fungal and even protozoal infections, much less success can be claimed by the industry in the development of safe and effective antiviral chemistries. This is in large part due to the fact that viral biology is integrally linked to host cell processes, and the control of these pathogens depends on finding effective approaches to blocking their entry into host cells, or interfering with virus-specific events in their replication and spread. Nearly all currently available antivirals work by blocking single molecular targets or events. Because viruses can mutate single or a few genes very rapidly, conventional antiviral chemistries lose therapeutic effectiveness due to viral resistance.
In sharp contrast, PLANTIVIRALS™ are predicted to be less susceptible to evolved virus resistance due to their lectin-like mode of action, which imparts a high binding affinity for carbohydrate structures on the surface of many viruses. These carbohydrate structures are used by viruses to block access of antibodies or other neutralizing host responses to the critical receptor-binding domain of the virus surface. Binding of PLANTIVIRAL™ lectins to viral surface carbohydrates disarms the virus, making it incapable of entering its host cell. Thus, in newly exposed individuals, PLANTIVIRALS™ would act by intercepting pathogenic viruses and preventing them from escalating the disease process. In chronically infected individuals, PLANTIVIRALS™ would act by binding free virus particles and minimizing or preventing spread and re-infection.
The novel mode of action of PLANTIVIRALS™ exploits a primary tactic in the virus host-defense repertoire, namely, to protect access to receptor domains through a carbohydrate shield. Thus, while development of resistance is theoretically possible, it is much less likely to occur because to overcome the action of PLANTIVIRALS™, viruses would need to mutate several independent genes–a low probability event–and simultaneously develop an entirely new approach to receptor domain shielding.
Furthermore, unlike most small-molecule-based antiviral drugs that are effective against only one or at best a relatively narrow range of viral pathogens, Intrucept’s PLANTIVIRALS™ have potential for use in a multitude of different clinical indications. PLANTIVIRALS™ thus could become the first truly novel broad-spectrum agents for antiviral chemotherapy and could be used alone or in combination with other classes of approved antiviral drugs, the latter for achieving synergistic control over difficult-to-treat viral infections.
