Virucidal Materials: From Synthesis to Function

There are millions of people that die of viral diseases (VDs) annually, rotavirus (diarrhea) kills ~1.8 million, HIV 2.5 million, and there are many more examples. The list is long and could become longer were new highly infective and/or deadly viruses to emerge (e.g. recent cases of Ebola, H1N1, or Zika). VDs can have devastating consequences even when they are non-lethal.

At present only a small subset of human VDs have approved drugs. Dengue, Diarrhea, RSV, Ebola, Zika, Influenza, and many others do not have drugs. The approved drugs almost exclusively have antiviral action that is they prevent infection by blocking viral replication intracellularly. Such antivirals tend to lose effectiveness upon viral mutations, are all virus specific, and -because of their intracellular mechanism - have some intrinsic associated toxicity. There are extracellular mechanisms to fight VDs, i.e. virustatic and virucidal. Drugs are said to be virustatic when they inhibit viral infection via a reversible extracellular mechanism. Unfortunately, the reversible nature of the binding mechanism makes all virustatic drugs medically irrelevant. Extra-cellular inhibition of viral infectivity via an irreversible mechanism is what defines virucidal drugs. There are many virucidal materials (e.g. surfactants, acids, bases) but these cannot be considered drugs as they are all extremely toxic. In general, harming a virus without being toxic to the host is a tall order, as the virus reproduces within the host and is mostly made of the same chemical components. The true breakthrough in this field would be to find broad-spectrum, non-toxic drugs. Virustatic and virucidal drugs have most of these attributes, but the former lack in-vivo efficacy and the latter are too toxic.

This project will focus on the development of new virucidal drugs based on a disruptive binding approach: binding to a virus so strongly as to induce local stresses that produce irreversible damage to the virus. Additionally, new and existing techniques will be utilised to study this novel approach to antivirals. Preliminary results have shown broad-spectrum, non-toxic virucidal nanoparticles and macrocycles with encouraging in-vivo data. However, the road to a real drug is long and full of hurdles; ranging from bio-distribution to clearance, or delivery approaches. To address these problems new materials will be synthesized that will allow for the attachment of sulfonate functional groups. Standard chemical characterization will confirm the formed structures. The testing of their interaction with viruses will follow using standard techniques such as dose response assays and serial dilutions. Combining these with flow-cytometry or plaque counting assays would quickly indicate their efficacy.