Characterization of the Spike protein of SARS CoV

• Applicant: Dr. Markus Eickmann
• Subject Area: Virology
• Term: from 2004 to 2006
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5437808

The overall structure of the SARS CoV genome is similar to that of the three known groups of coronaviruses. It encodes the structural proteins previously described with all other coronaviruses, namely spike protein (S), envelope protein (E), membrane protein (M) and nucleoprotein (N). Convalescent sera from SARS patients detect the proteins S and N. However, the overall homology to coronaviruses groups 1, 2 and 3 is low, and therefore the SARS virus does not closely resemble any of the three known groups of coronaviruses. The S protein plays an important role in virus entry, virus-receptor interaction and cellular tropism. All these functions are crucial for viral infectivity. Therefore, the S protein may present a target for prophylactic intervention in combating SARS. The S protein is unusually large, highly N-glycosylated and C-terminally inserted into the virus membrane. For some coronaviruses it has been clearly shown that S is cleaved by host-encoded proteases into the subunits S1 and S2. S1 has a globular folded domain and contains most likely the receptor-binding domain and the virus neutralizing epitopes, while S2 is thought to merge virus envelope with cellular membranes. For the SARS-CoV it is an open question whether the S protein is cleaved by host-encoded proteases. The aims of the overall project are, (1) to characterize the S protein from different virus isolates in respect to its function and antigenicity, (2) to find out whether the S protein undergoes proteolytic cleavage, whether cleavage is necessary for gaining fusion capacity of S2, to identify the corresponding cellular protease(s), (3) to analyze cell surface components (proteins, carbohydrates, lipids) as possible candidates for virus receptors, and (4) more generally to analyze interactions of host cell factors and SARS CoV gene products, predominantly protein S, as diagnosis markers and/or drug-targets for SARS.

• DFG Programme: Research Grants
• International Connection: China
• Participating Person: Professor Dr. Bing Sun