Screening for novel inhibitors of SARS-CoV-2 infection

3G10 antibody staining (green) for Heparan Sulfate on HUES7 cells following Heparinase III digestion (image courtesy of the Merry Lab, University of Nottingham UK. (DAPI blue and Phalloidin purple)

AMSBIO is reporting on the pioneering work by researchers at the University of Sheffield, UK, to measure the interaction between the SARS-CoV-2 Spike S1 protein receptor binding domain (SARS-CoV-2 S1 RBD) and heparin. This has resulted in a new assay which could be a useful first screen for novel inhibitors of coronavirus infection.

Evidence is mounting that SARS-CoV-2 uses heparan sulfates (HS) during the initial attachment to host cells, and this interaction appears to increase the affinity for the critical receptor, ACE2. The viral spike protein has a high affinity for heparin, particularly unfractionated heparin (UFH).

Dr. Peter Monk, Professor of Immunology at the University of Sheffield Medical School, commented "We have shown that sub-prophylactic doses of UFH can inhibit spike protein interactions with host cells whereas low molecular weight heparins (LMWH) such as enoxaparin and dalteparin are less effective. These findings have implications for the treatment of Covid-19. Current treatment often involves the administration of LMWH in the later stages when widespread blood clotting occurs. Earlier administration of UFH, or the delivery of nebulized heparin directly to the worst-affected organ, the lungs, may be an interesting therapeutic intervention to explore".

Adding to its comprehensive range of coronavirus research tools, AMSBIO now offers a suite of high quality Heparan Sulfate (HS) antibodies. These HS antibodies include F69-3G10, F58-10E4, and JM403 clones, which have been proven useful for targeted detection of varying levels of sulfated HS specific thought to be important in virus attachment.

Heparan Sulfate, also available from AMSBIO, is synthesized as the glycosaminoglycan (GAG) component of Heparan Sulfate Proteoglycans. It is expressed on the cell surface of virtually all cell types and basement membranes in mammals. It displays specific interactions with many biologically active proteins and, thus, is involved in many important biological processes. The non-immunogenic character of HS makes raising antibodies to this target very difficult, so the few hybridoma-derived mouse anti-HS antibodies such as JM403, 10E4, and 3G10 are valuable tools for HS research.

AMSBIO has produced an 'Applications Guide for Heparan Sulfate Antibodies' that brings together a wide range of information including protocols, results, and citations from customers working in this area.

Further information on the research group led by Professor Peter Monk can be found here.

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