K5 polysaccharides inhibit SARS-CoV-2 infection by preventing spike-proteolytic priming.

ingentiumby ingentium

In Coronavirus Literature.

K5 polysaccharides inhibit SARS-CoV-2 infection by preventing spike-proteolytic priming.

Publication date: Jan 09, 2026

SARS-CoV-2 spike glycoprotein is a promising drug target due to its crucial role in viral infection. Heparin, a long linear polysaccharide that inhibits SARS-CoV-2 infection by acting on spike, has limited antiviral applications due to its anticoagulant effect. E. coli K5 polysaccharides share the same structure as the heparin precursor and can be chemically modified to be devoid of anticoagulant activity. Here, biochemical assays and computer simulations reveal that K5 with high degree of sulfation at O- (K5OSH) or N- and O-positions (K5NOSH) bind spike with higher affinity than heparin, preventing its binding to ACE2 and furin cleavage. This mechanism is supported by cell syncytia assays showing that K5OSH and K5NOSH inhibit viral infection by blocking membrane fusion. Infection assays for SARS-CoV-2 Wuhan-Hu-1 and Omicron BA. 1 variants corroborate their antiviral activity. These results support the therapeutic potential of K5OSH and K5NOSH against SARS-CoV-2, with K5OSH displaying more promising activity profile.

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Concepts Keywords
Devoid Activity
Drugs Antiviral
Glycoprotein Assays
Promising Cov
Viruses Heparin
Infection
Inhibit
K5nosh
K5osh
Polysaccharides
Preventing
Promising
Sars
Spike
Viral

Semantics

Type Source Name
disease MESH SARS-CoV-2 infection
pathway REACTOME SARS-CoV-2 Infection
disease MESH viral infection
drug DRUGBANK Heparin
disease MESH Infection
disease MESH severe acute respiratory syndrome
drug DRUGBANK Glycine
pathway KEGG Virion
drug DRUGBANK Angiotensin II
drug DRUGBANK Serine
disease MESH Infectious Diseases
drug DRUGBANK Sulfate ion
drug DRUGBANK Prothrombin
drug DRUGBANK Coenzyme M
drug DRUGBANK Pentaerythritol tetranitrate
disease MESH dissociation
drug DRUGBANK Aspartame
disease MESH NTD
disease MESH MST
disease MESH andD
disease MESH included
drug DRUGBANK ATP
drug DRUGBANK Isoxaflutole
disease MESH bleeding
disease MESH strains
drug DRUGBANK Hydroxide ion
disease MESH MWs
drug DRUGBANK Tromethamine
drug DRUGBANK Phosphate ion
disease MESH PBS
drug DRUGBANK Cysteamine
drug DRUGBANK Dextran
disease MESH pyl
disease MESH NHS
drug DRUGBANK Edetic Acid
drug DRUGBANK Sodium lauryl sulfate
disease MESH SDS
disease MESH HBD
drug DRUGBANK Histidine
drug DRUGBANK Biotin
disease MESH theS1
drug DRUGBANK Water
drug DRUGBANK Flunarizine
drug DRUGBANK Activated charcoal
drug DRUGBANK Oxygen
drug DRUGBANK Nitrogen
drug DRUGBANK Benzylpenicillin
drug DRUGBANK Streptomycin
disease MESH FBS
disease MESH glass
drug DRUGBANK Formaldehyde
disease MESH PLAN
drug DRUGBANK Medical air
disease MESH image
disease MESH BLS
drug DRUGBANK Gentian violet cation
drug DRUGBANK Ethanol
drug DRUGBANK Proline
disease MESH Thrombosis
drug DRUGBANK Diethylstilbestrol
disease MESH Des
disease MESH LPS
disease MESH cancer
disease MESH Papa
disease MESH reperfusion injury
drug DRUGBANK Amber
pathway KEGG Endocytosis
pathway REACTOME Reproduction

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