Using heparin molecules to manage COVID-2019

Abstract

The coronavirus disease 2019 (COVID-19) pandemic is becoming one of the largest global public health crises in modern history. The race for an effective drug to prevent or treat the infection is the highest priority among health care providers, government officials, and the pharmaceutical industry. Recent evidence reports that the use of low-molecular-weight heparin reduces mortality in patients with severe coronavirus with coagulopathy. Although the full scope of the benefits from heparin for COVID-19 patients is unfolding, encouraging clinical data suggest that heparin-like molecules may represent a useful approach to treat or prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The intent of this article is to offer our opinions on the mechanism(s) by which heparin may attenuate the course of SARS-CoV-2 infection. Furthermore, we propose a novel strategy to treat or prevent SARS-CoV-2 infection using "designer" heparin molecules that are fabricated using a synthetic biology approach.

Keywords: COVID‐19; chondroitin sulfate; coagulation; heparan sulfate; heparin.

FIGURE 1

Function of heparan sulfate (HS) and HS proteoglycan. HS proteoglycan (HSPG) consists of a core protein and HS polysaccharide chains. The core protein contains a transmembrane domain that presents HS on the cell surface. Some HSPGs are present in the extracellular matrix. HS chains interact with antithrombin to interact with factor Xa (FXa) or factor IIa (FIIa) to regulate coagulation. These chains also bind to chemokines that recruit leukocytes to participate in inflammation. Many viruses bind to HS on host cell surfaces as the initial step to establishing infection. Chemical structures of the disaccharide repeating unit of HS are shown. GlcA, glucuronic acid; GlcNA, N‐acetyl glucosamine; GlcNS, N‐sulfo glucosamine; IdoA, iduronic acid

FIGURE 2

Chemical structures of heparan sulfate (HS) oligosaccharides and chondroitin sulfate E (CS‐E) oligosaccharides. A, The structure of HS 6‐mer, HS 12‐mer, and HS 18‐mer. HS 6‐mer and 12‐mer have antifactor Xa (FXa) activity. HS 18‐mer does not have anti‐FXa activity, but it binds to high‐mobility group box 1 to display anti‐inflammatory activity to protect liver injury induced by acetaminophen. Panel B shows the chemical structures of CS‐E 7‐mer and CS‐E 19‐mer. The CS‐E 19‐mer does not have anti‐FXa or anti‐IIa activities, but it attenuates the organ damage induced by bacteria lipopolysaccharide. The glycosidic linkages in HS and CS‐E oligosaccharides are also indicated