Attenuation of SARS-CoV-2 infectivity and hyperinflammation in Covid-19 by heparin-related polysaccharides (Minskad infektivitet av SARS-Cov2 virus och Covid19 hyperinflammation med heparin-relaterade polysackarider)

Low molecular-weight heparin (LMWH) has rapidly become a primary drug in treatment of Covid-19 patients. A major rationale is the pulmonary coagulopathy typical of the seriously ill patient. Increasing attention is also aimed at the acute inflammation ("cytokine storm") believed to precede the coagulation disorder. Heparan sulfate (HS), structurally related to heparin, binds the Sars-CoV-2 spike protein and thus serves as a co-receptor for the invading virus at target cells, and further, as a scaffold for cytokines involved in inflammatory processes.Owing to its higher degree of sulfate substitution, LMWH polysaccharide will compete with cell-surface HS for protein binding, and thus display anti-viral as well as anti-inflammatory activity. Attempts to exploit these activities in Covid-19 therapy are hampered by potential bleeding complications at high dosage of anti-coagulant LMWH. The anti-coagulant activity is associated with a specific structural feature that can be selectively eliminated by chemical modification. The resultant anti-coagulant-deactivated heparin (ADH) can be administered at higher dosage without any adverse effects. The project will compare various ADH preparations for anti-viral and anti-inflammatory activities. The overall aim is to select a drug candidate that can be combined with regular LMWH for optimal display of all relevant activities, which has a novel mechanism for attenuation of viral infection and hyperinflammation in Covid-19 patients. Läkemedelskemi; Medicinsk bioteknologi (inriktn. mot cellbiologi (inkl. stamcellsbiologi) molekylärbiologi, mikrobiologi, biokemi eller biofarmaci); Biokemi och molekylärbiologi