March 10, 2020

Scripps Research scientists tackle COVID-19 coronavirus epidemic from many angles Ongoing studies reveal important information about how the virus spreads and infects the body, and point to different approaches for potential vaccines and medicines.

March 10, 2020

Scripps Research scientists are pursuing multiple lines of research aimed at understanding and helping to mitigate the impact of the novel coronavirus behind the COVID-19 epidemic that has spread across the globe. They are tracing how the virus originated and spreads, exploring how it invades the body and how the immune system responds, and working to develop potential vaccines and medicines against the virus.

What is coronavirus?

Coronavirus is the family of viruses that causes outbreaks of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), two illnesses that emerged within the last two decades. Symptoms of coronavirus infections include flu-like symptoms such as fever, cough and shortness of breath.

The virus behind the current epidemic, called SARS-CoV-2, is a previously unknown member of the coronavirus family. The epidemic, which began in the Chinese city of Wuhan, has spread to every continent but Antarctica and has sickened tens of thousands of people, resulting in several thousand deaths as of early March 2020.

How did this virus originate, and how does it spread?

Kristian Andersen, PhD, a Scripps Research genomic epidemiologist and associate professor in the Department of Immunology and Microbiology, is tracing the origins of the novel coronavirus genome based on public sequencing data.

An immunologist by training and an expert in computational viral genomics, Andersen has worked on a number of highly infectious pathogens including Ebola, Lassa, Zika, West Nile and coronaviruses.

He and his colleagues are focusing in on several telltale features of the novel virus, including the spike protein the virus uses to connect to and enter cells. By comparing these features to those of previously known coronaviruses and those newly found in animals, they are reconstructing the origins of SARS-CoV-2.

They are also working with colleagues across the globe to better understand how the virus is transmitting in the human population from its beginning in China to its current spread around the world.

How does the novel coronavirus interact with our immune system? Can this knowledge help us fight the virus?

Researchers in the Scripps Research laboratory of Dennis Burton, PhD, chair of the Department of Immunology and Microbiology, are studying the human immune response to SARS-CoV-2 infections. This includes looking at how the cells of the immune system including B cells and T cells respond to the virus, how long patients continue to shed the virus after infection, and how much virus is produced in the cells of infected people.

The researchers are also looking for antibodies to the virus. Antibodies are molecules the immune system uses to identify and defuse pathogens such as viruses and bacteria. In particular, researchers are looking for potent antibodies called broadly neutralizing antibodies, which might serve as the basis for vaccines or antiviral therapies against COVID-19.

Andrew Ward, PhD, a professor of Integrative Structural and Computational Biology at Scripps Research, has a longstanding interest in understanding immune responses to coronaviruses, particularly how the body responds to the surface spike protein on the virus. These proteins are the target for antibodies that neutralize the virus.

Ward's team revealed the first structure of a human coronavirus spike protein in 2017 from the HKU1 virus, and subsequently went on to describe spike proteins from SARS and MERS the latter when it was connected with a neutralizing antibody.

They are now investigating the structure of the SARS-CoV-2 spike protein and working with collaborators in the United States who are isolating antibodies from infected patients.

The next step will be solving additional structures of the antibodies that bind to the spike protein to determine how they work and provide insights that may help create immunotherapies. They will also be testing whether SARS antibodies from the earlier coronavirus outbreak react with the novel coronavirus and could be used for treatment.

Lastly, Ward's group has developed new imaging methods that work as a diagnostic tool to directly probe blood samples from infected patients. This allows them to determine the types of antibodies patients generate. By focusing on the coronavirus spikes, they hope to lay the groundwork for new therapies in the short term and potential vaccines in the long term.

Can we make a vaccine for COVID-19?

Scripps Research professor Michael Farzan, PhD in his office on the Jupiter, FL campus of Scripps Research.

LINK:	https://www.scripps.edu/news-and-events/press-room/2020/20200310-covid...
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