UT Southwestern scientists discover potential vulnerabilities in new coronavirus

UT Southwestern Medical Center data scientists analyzing genetic sequences of the COVID-19 coronavirus have identified potential vulnerabilities that could help in vaccine development and further study of the infectious disease now spreading worldwide.

Specifically, the researchers point to areas where the viral genome encodes T cell and B cell antigens that could stimulate a response from the human immune system. They then compared those against the immunological maps of the severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) gathered in those coronavirus outbreaks. The resulting analysis was posted to the bioRxiv preprint server this week prior to peer review.

"Few studies have reported on the immunological features of this new coronavirus. Our analyses in this respect could serve as a reference resource for immunological studies and for potential therapeutics and vaccine development," says Yang Xie, Ph.D., director of the Quantitative Biomedical Research Center (QBRC) and a professor of population and data sciences and in the Lyda Hill Department of Bioinformatics. Scientists in China made the virus sequences available in January.

Although mutations in this virus' genome are still very limited, they locate in genomic regions whose homologous counterparts in SARS and MERS are proved to be highly mutated, indicating these regions are potential mutation hot spots to watch out for."

Tao Wang, Ph.D., assistant professor of population and data sciences and an investigator in the Center for the Genetics of Host Defense

Immunologists and vaccine designs should take these into consideration, as mutations will significantly affect the potential of the viral proteins to stimulate the immune system, the authors say.

Related research projects:

  • The QBRC scientists also created a publicly available web browser with an immune vulnerability map of the COVID-19 virus to facilitate study of the disease by research groups worldwide.
  • John Schoggins, Ph.D., associate professor of microbiology, is studying how mammals – including humans, mice, and bats – control viral infections. Bats can harbor numerous viruses without becoming sick. Schoggins (pronounced sk-ah-gins) is exploring whether the bat immune system contributes to their being asymptomatic viral reservoirs. His work on immune responses centers primarily on a signaling molecule – interferon – that "calls in the cavalry" to help cells mount their antiviral defenses and block the infection. This "cavalry" consists of hundreds of interferon-stimulated genes (ISGs), each with specialized functions tailored to cripple viruses in very unique ways. The Schoggins lab has pioneered various screening platforms, including CRISPR screens, to rapidly screen hundreds of ISGs for antiviral activity targeting a diverse panel of human viruses, including emerging viruses like coronavirus and Zika virus. J Immunol. 2018 Jan 1;200(1):209-217.
Source:
Journal reference:

Zhu, J., et al. (2020) Profiling the immune vulnerability landscape of the 2019 Novel Coronavirus. bioRxiv. doi.org/10.1101/2020.02.08.939553.

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