With resistance to the currently available flu anti-virals Relenza and Tamiflu increasing, scientists at St Andrew’s University in Scotland are proposing an alternative approach, using a sialic acid binding fusion protein, which binds to sialic acid binding sites and blocks them.
This targets the host rather than the virus, overcoming the drug resistance that is a major problem with the fast-evolving influenza virus. The approach has advantages over removing sialic acid receptors with sialidase, as this approach can unmask hidden receptors for other respiratory pathogens.
The scientists have developed multivalent proteins based on the sialic acid binding domain of Vibrio cholerae sialidase that have varying binding affinities from micromolar to nanomolar.
These proteins recognize terminal sialic acids, independent of linkage (α(2,3), α(2,6), and α(2,8)), and hence bind to receptors in the respiratory tract that are recognised by avian or human viruses. As a result, the virus is prevented from attaching to its receptor in the initial stages of infection.
This methodology overcomes pathogen resistance from fast-mutating viruses. As a prophylactic therapy the recombinant proteins could be used during the period when no vaccine was available, and provide protection against the spread of new virus strains.
The researchers consider the recombinant protein would be amenable to an intranasal delivery.
A therapy based on this technology would be active against all currently circulating and future strains of influenza A and B viruses, including avian H5N1, and H1N1 (“swine flu”).
St. Andrews has applied for patent protection and this entered the PCT phase in September 2009. The university would welcome enquiries from anyone interested in entering into commercial discussions in regard to developing the recombinant proteins as antiviral treatments. Further information/discussions would be held under a confidentiality agreement.
For more information, visit the project’s page at: http://www.university-technology.com/details/receptor-binding-molecules-as-therapeutics-against-respiratory-pathogens