A Novel Antiviral Method and Screen for Antiviral Agents

These inventions disclose (1) a novel method to disinfect virus by immobilizing anti-infective agents on a carrier surface such as microparticles or nanoparticles; (2) an effective multicycle assay for screening the anti-infective agents. The coated particles, termed protocells, can attract and inactivate virus by triggering the false activation of the viral fusion protein. These inventions provide a technology platform for the development of a series of products to treat and prevent viral infections.

Technical Merits

The researchers have demonstrated that protocells bearing the entry receptor for henipaviruses, EFNB2, reduce the titer of infective virus in cell culture, as measured by reduction in the titer of pseudotyped virions. The inhibition is specific; only EFNB2-bearing, but not EFNB1-bearing, protocells are inhibitory, and the inhibitory effect is specific for henipaviruses. Viral inactivation by these protocells requires interaction with EFNB2 receptor, but is not attributable to binding alone. The protocells are not saturatable and can exert an ongoing inhibitory effect over time, suggesting that they could provide a reusable antiviral strategy that would remain active for extended periods of time. This feature is advantageous in addressing infection with henipaviruses and applies to other enveloped viruses. The multicycle assay simulates multicycle replication and thus identifies inhibitors that target several stages of the viral life cycle, but it still can be carried out under biosafety level 2 (BSL-2) conditions. These features permit a screen for antivirals of emerging viruses and select agents that otherwise would require BSL-4 HTS facilities.

Potential Applications

Viral infections are not currently treated with antibiotics. Antiviral therapy is mostly intended to treat symptoms while the body's own immune defenses work at eradicating the virus. Most of the antiviral agents now available are limited to treating HIV, herpes viruses, the hepatitis B and C viruses, and influenza A and B viruses. Cornell's novel antiviral method provides:

A versatile platform for developing novel antiviral agents to treat and prevent infections of virus and other pathogens

• High Throughput screening assay for inhibitors that target several stages of the viral life cycle