Product name
Influenza: PB2 cap-binding site as new target and compounds offered by EMBLEMSummary
Precise definition of PB2 cap-binding site, in vitro HTS and hit stage compounds availableOrganization name
EMBLEM - the commercial arm of the European Molecular Biology LaboratoryProfile
Current state of anti-influenza virus drug design
Crystal structure determination of Neurominidase (NA) led directly to the development of novel neuraminidase inhibitors with anti-viral activity. These and their derivatives have subsequently been developed into anti-influenza drugs zanamivir (Glaxo) and oseltamivir (Roche), which are currently being stockpiled by many countries as a first line of defence to an eventual pandemic.
The currently available neuraminidase inhibitors block virus spread but not virus replication and provide only a reduction in the duration of clinical disease. Thus, the efficacy of the anti-neuraminidase drugs in treating a highly virulent and contagious mass influenza epidemic is unknown. In addition, resistant viruses are rapidly selected in patients treated with these inhibitors, although less efficiently than with M2 inhibitors such as amantadine. Clearly, new antiviral compounds are needed that should be directed to a different virus target.
The polymerase complex is such a target, since it is essential for viral replication and contains several functional active sites likely to be significantly different from those found in host cell proteins. Some potential anti-viral compounds targeting the cap-binding site, endonucleolytic active site, chain elongation or other functions of polymerase and exhibiting selectivity over host cell enzymes have been reported.
Technology
Results from EMBL Grenoble allow for the first time:
- the precise definition of the PB2 capbinding site within an independently folded domain. It has up till now been highly controversial where the site is and whether it exists independently to the other subunits and the viral RNA,
- in vitro high-throughput screening for inhibitors of a functional site from influenza virus polymerase using easily obtainable material from a straightforward E. coli expression system,
- structure based approaches to cap-binding inhibitor design, i.e. in silico screening and lead optimization by crystal structure determination.
Commercial Opportunity
Development of a potent small molecule treatment of Influenza
- Development of novel inhibitors of influenza virus replication based on the precise knowledge of a highly conserved PB2 cap-binding site based on structural design.
- Expression technology to generate protein for the screening of novel inhibitors of influenza virus replication using recombinant expressed PB2-capbinding site.
- Medicinal Chemistry on first screening hits
Development Status
Available are: Screening assay, Crystal structure coordinates, Compounds (hit stage)
Patent applications has been filed.
Contact
EMBLEM
Dr. Martin Raditsch
Raditsch(at)embl-em.de
About EMBLEM
EMBL Enterprise Management Technology Transfer GmbH (EMBLEM) is an affiliate and the commercial arm of the European Molecular Biology Laboratory (EMBL). EMBLEM, established in 1999 identifies, protects and commercialises the intellectual property developed in the EMBL-world, from EMBL-alumni and from third parties. EMBLEM facilitates and accelerates the transfer of innovative technology from basic research to industry by working closely with industrial partners spanning the biotech, ITC and mechanical/electrical engineering markets to develop new diagnostics, drugs, therapies and machines and devices.
Description File
INFLUENZA_-_NEW_TARGET___COMPOUNDS.pdf
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