LITTLE ROCK — A University of Arkansas for Medical Sciences (UAMS) research team has found that while the coronavirus can create dangerous variants like delta and omicron, its ability to mutate has limits that should help drug and vaccine makers trying to thwart it.
Drawing from global databases with millions of sequenced SARS-CoV-2 genomes, the multinational team, led by David Ussery, Ph.D., has shown that the virus has a limited genetic range for new mutations. The team’s observations are published in FEMS Microbiology Reviews.
“The surprising finding is that the virus is pretty stable, and it is not changing that much,” said Ussery, professor and director of the Arkansas Center for Genomic Epidemiology & Medicine at UAMS. “It’s somewhat restricted. That’s good news for designing drugs that can fight it effectively.”
The virus’ structure makes it slower to mutate and gives it fewer mutation possibilities. Ussery contrasted it with HIV as an example of a virus that is much more adept at evading new drug therapies. A typical viral escape mechanism has to do with regulation of its production of epitopes, which are protein segments of different shapes that antibodies bind to as part of the immune defense.
“Instead of the frightening theoretical possibility of this virus producing millions of different epitopes that need to be therapeutically anticipated during vaccine development, we may now be able to predict a very limited subset of probable epitopes,” Ussery said.
The team analyzed coronavirus genomes in GenBank and Global Initiative on Sharing Avian Influenza Data (GISAID) databases. It used the high performance UAMS-based computer known as GRACE to perform much of the computational work. The infrastructure to help run this computer is supported in part by a grant from the National Science Foundation (NSF) in 2020, “Data Analytics That Are Robust and Trusted (DART).” This was an Arkansas state-wide grant ($24 million), funded by the Arkansas NSF EPSCoR program.
Ussery, who holds the Helen Adams & Arkansas Research Alliance (ARA) Endowed Chair in Biomedical Informatics, said the analysis was inspired by “Ebolavirus Comparative Genomics,” published in 2015 by an international team that included all four authors of the COVID-19 paper. The Ebola publication earned a FEMS Microbiology Reviews Editor’s Choice Award.
“I think our SARS-CoV-2 findings are breaking some new ground, helping people see the big picture with a systematic look at the virus’ genomics,” Ussery said. “We now have several million genomes and that allows us to tease out the variance within different lineages that are causing major outbreaks like delta and omicron.”
The research team was also able to identify numerous incomplete or erroneous sequences housed in the databases. In addition to Ussery, the co-authors are:
- Trudy Wassenaar, Ph.D., (first author) director of Molecular Microbiology and Genomics Consultants, Zotzenheim, Germany
- Visanu Wanchai, Ph.D., currently a post-doctoral fellow, Department of Biomedical Informatics, UAMS College of Medicine
- Gregory Buzard, Ph.D., microbiologist (retired from Centers for Disease Control and Prevention)
This work was supported in part by the National Institute of General Medical Sciences at the National Institutes of Health, grant 1P20GM121293. It has also received support from the UAMS Translational Research Institute, which is supported by the National Center for Advancing Translational Sciences Clinical and Translational Science Award UL1 TR003107; and by a NSF Award (No. OIA-1946391), and with funding from the Arkansas Research Alliance.
UAMS is the state’s only health sciences university, with colleges of Medicine, Nursing, Pharmacy, Health Professions and Public Health; a graduate school; a hospital; a main campus in Little Rock; a Northwest Arkansas regional campus in Fayetteville; a statewide network of regional campuses; and seven institutes: the Winthrop P. Rockefeller Cancer Institute, Jackson T. Stephens Spine & Neurosciences Institute, Harvey & Bernice Jones Eye Institute, Psychiatric Research Institute, Donald W. Reynolds Institute on Aging, Translational Research Institute and Institute for Digital Health & Innovation. UAMS includes UAMS Health, a statewide health system that encompasses all of UAMS’ clinical enterprise.
UAMS is the only adult Level 1 trauma center in the state. U.S. News & World Report recognized UAMS Medical Center as a Best Hospital for 2021-22; ranked its ear, nose and throat program among the top 50 nationwide for the third year; and named five areas as high performing — colon cancer surgery, diabetes, hip replacement, knee replacement and stroke. Forbes magazine ranked UAMS as seventh in the nation on its Best Employers for Diversity list. UAMS also ranked in the top 30% nationwide on Forbes’ Best Employers for Women list and was the only Arkansas employer included. UAMS has 3,047 students, 873 medical residents and fellows, and six dental residents. It is the state’s largest public employer with more than 10,000 employees, including 1,200 physicians who provide care to patients at UAMS, its regional campuses, Arkansas Children’s, the VA Medical Center and Baptist Health. Visit www.uams.edu or www.uamshealth.com. Find us on Facebook, Twitter, YouTube or Instagram.
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