Glycan-based antivirals against SARS-CoV-2 and future pandemic viruses (Glykan-baserade antivirala medel mot SARS-CoV-2 och framtidens pandemiska virus)

Purpose: Identify and develop novel, sialic acid-containing antiviral drugs against SARS-CoV-2 causing COVID-19.Work plan: The approach is very straight forward. My lab has previously identified glycosaminoglycans (GAGs) and sialic acid (SA)-containing glycans as receptors, co-receptors, and decoy receptors for multiple other, unrelated viruses. Some coronaviruses use glycans as receptors, but there are no reports about SARS-CoV-2 using glycans as receptors or co-receptors. Supported by preliminary data, we will: i) screen a number of GAGs and SA-based glycans for interaction with SARS-CoV-2 spike protein by surface plasmon resonance and by flow cytometry, and ii) investigate if compounds with high affinity inhibit SARS-CoV-2 infection using an advanced, 3D air-liquid-interface (ALI) model of the human lung. We will also investigate the role of glycans as functional receptors/co-receptors for SARS-CoV-2 using the 3D ALI  lung model.Impact: As some of the compounds included in this study have already been demonstrated to to be safe in humans and/or to be non-toxic in animals, this research proposal has a realistic chance to translate into improved treatments of COVID-19 within a year. Mikrobiologi inom det medicinska området; Infektionsmedicin; Medicinsk bioteknologi (inriktn. mot cellbiologi (inkl. stamcellsbiologi) molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)