Effective Inhibition of SARS-CoV-2 Entry by Heparin and Enoxaparin Derivatives
Ritesh Tandon, Joshua S. Sharp, Fuming Zhang, Vitor H. Pomin, Nicole M. Ashpole, Dipanwita Mitra, Martin G. McCandless, Weihua Jin, Hao Liu, Poonam Sharma, Robert J. Linhardt
Abstract
The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV-2) in Wuhan, China, in late 2019 and its subsequent spread to the rest of the world has created a pandemic situation unprecedented in modern history. While ACE2 has been identified as the viral receptor, cellular polysaccharides have also been implicated in virus entry. The SARS-CoV-2 spike glycoprotein (SGP) binds to glycosaminoglycans like heparan sulfate, which is found on the surface of virtually all mammalian cells. Here, we report structure-based differences in antiviral activity and affinity to SGP for several sulfated polysaccharides, including both well-characterized FDA-approved drugs and novel marine sulfated polysaccharides, which can be developed for prophylactic as well as therapeutic purposes.