A. Diwan, S. Brauer
Nanotech Plus, LLC,
United States
Keywords: broad spectrum, antiviral, polymer, therapeutic, prophylactic
Summary:
Synthetic polymers offer an interesting alternative to biopolymers as therapeutic compounds. This poster explores recent applications as broad spectrum antiviral drugs. One approach to stop viral reproduction is to prevent the virus from initially entering the cell. There are two potential targets: the entry mechanism of the cell which the virus utilizes, or the docking site on the virus. To date, viral entry inhibitors focused only on the virus, but unfortunately, these compounds do not have broad spectrum activity. Recently, research focused on the cell surface rather than the virus. Fortunately, viruses use only a few types of moieties on cell surfaces for their initial docking such as heparin sulfate or sialic acid. Since directly blocking these sites leads to toxicity, a different approach is needed. Nanoparticles, decorated with ligands that “spoof” the cell surface, are extremely promising candidates for broad spectrum antiviral drugs. Professor Francesco Stellacci of EPFL (Swiss Federal Technology Institute of Lausanne), showed that by using many weak bonds, rather than a few strong bonds, viruses bind reversibly, reducing toxicity. Upon binding, the virus disassembles itself. NanoViricides, (www.nanoviricides.com) located in Shelton, CT, pursued this strategy for decades to develop broad spectrum antiviral drugs. The technology involves three components: 1) A highly mobile polymer (common to all NanoViricides’ drugs) 2) A linker molecule 3) Ligands that decorate the surface mimicking where the virus binds initially. Once the virus binds to the nanoparticle, the polymer flows and coats the virus which causes it to disassemble. The company developed several compounds which demonstrated dramatic efficacy in animal models. Recently, the company conducted a Phase 1 clinical trial of its compound, NV-387 which showed that the drug was very well tolerated with negligible side effects. NV-387 has shown efficacy against respiratory viruses including: influenza, RSV, coronaviruses, and orthopox viruses (mpox). This wide applicability demonstrates the potential of a broad spectrum antiviral drug using the approach of spoofing cell surfaces, rather than attacking the virus directly. NanoViricides has its own U.S.-based R&D and small scale manufacturing facility to ensure that producing these compounds can be reproducible and secure. NanoViricides drugs have applications beyond conventional antivirals as they can be used prophylactically as well as therapeutically. Prophylactic applications should be of great interest for the warfighter as this technology will help reduce risk if viral bioweapons are deployed on the battlefield. Prophylactic applications should also be of interest to researchers working with potentially infectious viruses, as they should reduce the likelihood of infection as well as minimizing the chances of viral escape. Therapeutic applications are straightforward as these compounds are well tolerated and should have minimal interactions with other drugs. For immunocompromised patients, these compounds represent a potential safer alternative to vaccination for common respiratory illnesses.