Our research

Research in the group focuses on virus/material interactions to improve our understanding of how viruses interact with their environment. By improving our understanding in this area, it has allowed us to develop several novel broad-spectrum virucidal antivirals. We have on-going research in the group related to viral vaccine stabilisation, triggered delivery, gene therapy and medical textiles. The group utilise a range of synthetic and biological techniqus such as small molecule and polymer synthesis, nanomaterial synthesis and bio-assays for studying cells and their viral infection. The group is also intersted in understanding the mechanism behind such interactions and utilises a range of biological assays to investigate this. 

Currently the group has synthesised a number of different materials that show potent virucidal antiviral inhibition against a wide range of viruses including Herpes Simplex Virus 1 & 2 (HSV-1 and HSV-2), Lentivirus (Human Immunodeficiency (HIV)-like virus), Human papilomavirus (HPV), Respiratory syncytial virus (RSV), Human parainfluenza virus type 3 (PIV3), Human metapneumovirus (HMPV), Dengue virus and Zika virus. The group continues to explore the effects of such antivirals against other viruses and their in-vivo efficacy. 

 

Why antivirals?

There are millions of people that die of viral diseases annually, rotavirus (diarrhea) kills ~1.8 million, HIV 2.5 million, to name just two. The list is long and could become longer if new highly infective and/or deadly viruses emerge (e.g. recent cases of Ebola, H1N1, or Zika). Viral diseases can have devastating consequences even when they are non-lethal. The best way to fight viral diseases is to develop and use vaccines. Unfortunately, vaccines are only available for a minority of viral diseases and, even when they are available, viral mutations can lead to them becoming ineffective. In a world of rapidly mutating viruses, vaccines alone might not always be the answer. When a person is infected a vaccine is useless, hence there is a great need for drugs against viral diseases. Rapid mutations and the probable emergence of new viruses, together with the high incidence of viral diseases in countries where diagnostic systems are scarce, create a specific need for drugs that are broad-spectrum, i.e. the equivalent of broad-spectrum antibiotics.

Antivirals

Anti-viral Darunavir - HIV protease inhibitor

At present only a small subset of human viral diseases have approved drugs. Dengue, rotavirus (Diarrhea), Respiratory synoptical virus (RSV), Ebola, Zika, Influenza, and many others do not have drugs. The approved drugs almost exclusively have antiviral action, which is they prevent infection by blocking viral replication intra-cellularly. Such antivirals tend to loose 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 viral diseases, i.e. virustatic and virucidal. 

 

virustatic vs virucidal

Drugs are said to be virustatic when they inhibit viral infection via a reversible extracellular mechanism. There has been a large body of research on virustatic drugs capable of binding to viral attachment receptors and by doing so inhibiting virus-cell interactions. One such example is Heparin. Heparin is a is a polymer with a molecular weight ranging from 3 to 30 kDa, that is produced by basophils and mast cells. Whilst most commonly used as an anticoagulant, Heparin is also able to reversibly inhibit virus/cell interactions. Such an inhibition mechanism is termed virustatic. Recently, many heparin inspired materials have shown the same virustatic broad-spectrum, non-toxic behaviour against viruses. Unfortunately, the reversible nature of the binding makes all virustatic drugs medically irrelevant. One of the reasons is that, upon dilution in bodily fluids below the binding constant, the drugs will be released from the virus and the intact virus will regain its infectivity.

 

Schematic representation of virustatic mechanism

 

Extra-cellular inhibition of viral infectivity via an irreversible mechanism is what defines virucidal drugs. Virucidal drugs, if they existed, are widely regarded as the best approach for treating viral infections as they act directly on the virus and thus severely reduce the possibility for a virus to develop resistance. 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.

 

Schematic representation of virucidal mechanism