Posted on February 28, 2016

There has been a major breakthrough in efforts to fight coronaviruses through solving the first low-resolution structure of human coronaviruses Spike trimer; a protein that enables the virus to enter host cells (Figure)*. The study was published in Journal “Nature” on 3rd March 2016, the world's most prestigious and highly cited interdisciplinary scientific journal, according to the 2013 Journal Citation Reports Science Edition Journal.

The paper titled Prefusion structure of a human coronavirus spike protein’ has been co-authored by Dr Hadi Mohamad Yassine, Assistant Professor of Infectious Diseases at Qatar University Biomedical Research Center (BRC). The paper features the first structure of human coronavirus (HKU1) spike protein. HKU1-CoV is one of six coronaviruses that infect human and it falls into the same group like SARS- and MERS-CoV (betacoronaviruses).

Infection with this virus results in mild respiratory illness but might lead to hospitalization in immunocompromised patients. The virus causes up to 5% of respiratory infections in humans and it was first identified in 2005 in a 71-year-old man who was hospitalized with an acute respiratory distress and radiographically confirmed bilateral pneumonia. Dr. Yassine was the one that initiated the project, designed and made the constructs and did the initial characterization of the protein.

QU faculty research study on [].jpg

Speaking during an interview, he said research about HKU1 virus had been hindered by the difficulty to grow the virus in typical cell culture systems. “The whole work was initiated to identify the receptor of the virus and establish serological assays to study virus immunogenicity” he added. Further, the large size of Spike protein and its extensive glycosylation have hindered structural studies of the full ectodomain, thus preventing a molecular understanding of its function and limiting development of effective interventions.

Accordingly, Dr. Yassine said he designed the Spike protein construct that went through rounds of modification until one yielded a good trimeric protein expression. “This finding triggered the idea of solving the structure of the protein, as there has been no structure available for any of the human coronaviruses spike trimers.” he further said. Through the collaboration of several centers, the structure was solved and the results were published in Nature Journal.

Dr. Yassine added that these findings would help in solving structures of other spike proteins, like those for MERS and SARS, and thus, would aid in developing a better vaccine candidates against these viruses, or any other coronavirus that might emerge in the future.

* The spike protein is the protein that gives the virus its “crown-shape” and it contains the receptor-binding domain.