Non-anticoagulant heparin derivatives for COVID-19 treatment

The ongoing pandemic of COVID-19, caused by the infection of SARS-CoV-2, has generated significant harm to the world economy and taken numerous lives. This syndrome is characterized by an acute inflammatory response, mainly in the lungs and kidneys. Accumulated evidence suggests that exogenous heparin might contribute to the alleviation of COVID-19 severity through anticoagulant and various non-anticoagulant mechanisms, including heparanase inhibition, chemokine and cytokine neutralization, leukocyte trafficking interference, viral cellular-entry obstruction, and extracellular cytotoxic histone neutralization. However, the side effects of heparin and potential drawbacks of administering heparin therapy need to be considered. Here, the current heparin therapy drawbacks were covered in great detail: structure-activity relationship (SAR) mystery, potential contamination, and anticoagulant activity. Considering these unfavorable effects, specific non-anticoagulant heparin derivatives with antiviral activity could be promising candidates to treat COVID-19. Furthermore, a structurally diverse library of non-anticoagulant heparin derivatives, constructed by chemical modification and enzymatic depolymerization, would contribute to a deeper understanding of SAR mystery. In short, targeting non-anticoagulant mechanisms may produce better therapeutic effects, overcoming the side effects in patients suffering from COVID-19 and other inflammatory disorders.