Thapsigargin II and Thapsigargin III derivatives for enhancing immune response to viral infection

Description:

Influenza/RSV immunomodulation therapy

Host-centric response reduces resistance

 

In brief:

Small molecule stimulates a highly effective host antiviral response against influenza virus and respiratory syncytial virus (RSV) which includes:

Interference of viral protein transport and assembly, and enhanced type I and III interferon response.

Compound can be orally administered, and is difficult for virus to overcome by mutation

 

Demonstrated protection in mice against lethal influenza challenge

At least as effective (1.5 µg/kg/day) as high dose oseltamivir (45 mg/kg/day) in vivo

Multi-faceted innate immune response not easily overcome by virus mutation

 

Flu virus readily gains resistance to current and new antivirals

Pandemics are an inevitable feature of influenza virus. Current antivirals work by directly targeting influenza virus proteins, such as viral neuraminidase and polymerase, and are highly vulnerable to resistance development due to mutations.

In such eventualities, both seasonal vaccines and existing antivirals are of limited value. Thus, there is the unmet need for antivirals to be more effective and resistant to viral mutations.

 

Triggering a multi-faceted host innate immune response

The small molecule activates a range of host innate immune mechanisms to block virus replication; such multi-layer defences are difficult for a virus to overcome by mutational changes.

The mode of action of the antiviral compound is completely different from all current and indevelopment influenza antivirals.

 

Key features:                             

• low dose required;

• high selectivity index (high safety margin);

• effective therapeutically and prophylactically

• No cytokine storm or histamine upregulation

 

 

The mode of action of the antiviral compound is completely different from all current and indevelopment influenza antivirals.

 

X triggers different host innate processes culminating in post-translational inhibition of virus replication.

These generic but effective host antiviral defences against influenza are just as effective against RSV. X has the potential to be applied to other RNA viruses.

In vivo studies have shown that the compound is protective against lethal viral challenge, and a relatively low dose is at least as effective as high dose (45mg/kg/day) oseltamivir.

 

Antiviral small molecule just as effective against RSV infection

These generic but effective host antiviral defences against influenza are just as effective against RSV. X has the potential to be applied to other RNA viruses.

 

 

 

Patent Information:
Category(s):
Healthcare
For Information, Contact:
Jonathan Gibbons
Senior Licensing Executive - Healthcare
The University of Nottingham
+44 (0) 115 82 32189
Jonathan.Gibbons@nottingham.ac.uk
Inventors:
Kin-Chow Chang
Keywords:
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