Elasmogen Ltd, the pioneering biopharmaceutical company leading the development of VNAR and soloMERTM biologics, announces a significant breakthrough in the identification of next-generation protein-based drugs potentially capable of stopping Covid-19 infections. This new approach has been achieved through a close partnership with the University of Minnesota, USA and represents an excellent example of the new spirit of research collaboration that has accelerated the global fight-back against Covid-19. Initial funding for this work was received from the Chief Scientist Group, Scottish Government and was co-ordinated through the University of Aberdeen.
The newly identified anti-Covid-19 Spike protein VNARs block infection of the virus (in live viral assays) at doses as low as 200 pM, equivalent to the best reported antibodies and much better than many. However, what is particularly exciting about Elasmogen’s drug panel is that they are only a 10th the size of large and complex (to manufacture) human antibodies and therefore could be delivered to patients through alternative routes of administration including directly into the nose and throat, rather than via injections.
A key advantage of Elasmogen’s VNAR platform is the ability to bind to their target at sites that are inaccessible to human antibodies translating, in many cases, to increased potency and specificity against the disease. By crystallising the lead VNAR as it bound to the receptor binding domain of the Covid-19 spike protein, the team were able to prove that the VNARs bound the virus/receptor interface in a region distinct from published antibodies, effectively blocking infection. Computer modelling discovered that this interaction would not be weakened if the VNAR was asked to block infections from the Kent or South African strains, although this has not yet been shown experimentally.
Dr Caroline Barelle (CEO and CSO, Elasmogen Ltd) explained: “These robust little proteins have their origins in the immune systems of sharks and over 400 million years of evolution have been tailor-made to recognise pockets and grooves in proteins as part of the animals defence against infections. At Elasmogen we have been able to capture, using the latest protein and genetic engineering techniques, the immune system of 10,000 shark equivalents in a test-tube. We then screened these for VNAR binders that block viral infection, and are delighted with the outcomes”.
Professor Aaron LeBeau (University of Minnesota Medical School, Department of Pharmacology): “Determining the structure of protein complexes by x-ray crystallography can often be a taxing process requiring months to years to get a structure. It was particularly satisfying that we were able to get a high resolution crystal structure in such a short amount of time, primarily due to the high solubility of the VNAR. Our structure was highly informative documenting that the VNAR bound to the receptor binding domain through a novel mode that neutralized virus infection. It was clear that the VNAR was reaching into places that large human antibodies and even small single domain camelid antibodies just could not access”.
Prof Andy Porter (Chief Technology Officer, Elasmogen Ltd): “We have used our drug-discovery platform in the past for the successful selection of potent anti-cancer drugs. However, we are so grateful to the Scottish Government for funding Elasmogen Ltd to see if the power of our platform could be redirected to potentially tackle Covid-19 infections. As the world begins to see a route out of the pandemic it is worth remembering that a small but significant sub-set of patients will not respond to vaccines effectively because of their underlying health conditions. It is therefore vital that we continue with drug discovery approaches in parallel with the global vaccination role out”.