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A new broad-spectrum antiviral

Viruses present an ongoing present and future threat to mankind. Few antiviral drugs or treatments have reached the clinic and virus resistance, as with all microorganisms, is a major problem where antivirals have been deployed. We have discovered how to harness a new generation of naturally-occurring antivirals produced by influenza A virus. One in particular, VH244, is highly active in preclinical tests against many different influenza A viruses, and also against other unrelated respiratory viruses. The next step is human testing in clinical trials.


Background

Despite the impact of virus infection on human health only a handful of antivirals have reached the clinic and levels of resistance against those that are available are rising. Defective interfering (DI) virus genomes are produced naturally by most viruses as a result of massive deletions to the infectious genome. All DI genomes have antiviral activity in the laboratory; they are not infectious and represent a wonderful and novel resource for treating human virus infections.

However, despite being known for decades, DI genomes have not been demonstrated to have convincing and consistent antiviral activity in vivo. The breakthrough happened at Warwick when Professors Nigel Dimmock and Andrew Easton demonstrated the efficacy of a particular influenza A DI RNA sequence (VH244) at preventing and treating not only influenza A but also disease caused by unrelated respiratory viruses. This is an unprecedented and unexpected breadth of activity.

The beauty of this system is that the DI genome is packaged in a normal virus particle, which is used as a delivery vehicle (via the nose) to take the antiviral to susceptible cells. This delivery is so specific that very low doses of VH244 are required, and only a single dose is needed for effective treatment. VH244 is fully effective immediately. VH244 protects from respiratory viruses by two totally different mechanisms: a form of molecular interference which is effective against the replication of influenza A viruses, and stimulation of host innate immunity which acts against non-influenza A viruses. Both antiviral mechanisms are equally effective. VH244 is a treatment, not a vaccine. However, the subclinical infection that results is sufficient to stimulate a long-lasting immunity which prevents reinfection by the infecting virus.

Impact

The work by Professor Dimmock and Professor Easton has been supported by the Wellcome Trust and the Medical Research Council. It has been published in international peer-reviewed journals as primary research and in reviews, and has been presented in scientific conferences worldwide and to non-scientists. VH244 has been protected by international patents. It is currently attracting the support of major venture capital funders to take it to clinical trials.

Future

VH244 is the first-example of its type, and is a low dose, single application medicine that can be used against all respiratory viruses. Because of its mode of action it is highly unlikely that resistance to VH244 will arise.

Antiviral Technology
DI virus