DyCoVin - Interactions and dynamics of SARS-CoV 2 spike-heparin complex

The project entitled "DyCoVin - Interactions and dynamics of SARS-CoV 2 spike-heparin complex", is led by Prof. Rebecca Wade from Heidelberg University, Germany. The spike glycoprotein 1 of SARS-CoV-2 (SG1-Cov2) mediates the binding of the coronavirus to human cell receptor angiotensin-converting enzyme 2 (ACE2). Along with this, heparan sulphate proteoglycans (HSPGs) are used as the first attachment site, leading to an increased concentration of viral particles on the target cell surface. Moreover, in vitro assays suggest that heparin can effectively prevent the coronavirus strain HSR1 from binding. The curious thing, in this case, is that heparin is a very old drug, discovered in 1916.It is an anticoagulant, preventing the formation of blood clots and growth of existing clots. It is used in the treatment of lung diseases such as pulmonary fibrosis, bronchial asthma and asthma-induced airway hypersensitivity, and recent clinical trials suggest that inhaled heparin for lung diseases is beneficial and safe. The objective of the project team is to pinpoint the role of HSPGs in spike SG1-Cov2 infection using realistic computer simulations. This knowledge will allow characterising the structure and dynamics of putative binding patches for heparin-like compounds on the spike receptor, which needs to adopt the open form to bind ACE2. For that reason, the team aims to stabilise the receptor using different heparin chains to shield binding sites and to decrease the flexibility of the spike. The researchers expect the impact of this approach for treating the viral infection to be high because the FDA already approved the heparin. That is why aerosol drug administration could provide the advantage of directly delivering heparin to the site of the SARS-CoV-2 infection and thereby to stop the interaction between the virus and the receptor. PRACE awarded the project with 3 520 000 core hours on Marconi100, hosted by CINECA, Italy.