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Significant Breakthrough Achieved in Identification of Next-Generation Protein-Based Drugs That Could Stop COVID-19 Infections

By HospiMedica International staff writers
Posted on 26 Jan 2021
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Researchers have identified a panel of novel, potent, anti-COVID-19 therapeutic candidates which, at only one tenth the size of traditional antibodies, could be used to both treat and protect against SARS-CoV-2 infections.

Elasmogen Ltd. (Aberdeen, Scotland), in partnership with the University of Minnesota (Minneapolis, MN, USA), has announced a significant breakthrough in the identification of next-generation protein-based drugs potentially capable of stopping COVID-19 infections. 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 crystallizing the lead VNAR as it bound to the receptor binding domain of the COVID-19 spike protein, the team was able to prove that the VNARs bound the virus/receptor interface in a region distinct from published antibodies, effectively blocking infection. Computer modeling 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.

“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 recognize pockets and grooves in proteins as part of the animals defense against infections,” said Dr. Caroline Barelle, CEO and CSO of Elasmogen Ltd. “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.”

“Determining the structure of protein complexes by X-ray crystallography can often be a taxing process requiring months to years to get a structure,” said Professor Aaron LeBeau from the University of Minnesota Medical School, Department of Pharmacology. “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.”

Related Links:
Elasmogen Ltd.
University of Minnesota



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