UNC School of Medicine Affiliates Are Working Together Across Disciplines on COVID-19 Research
UNC Health Care
Ralph Baric’s lab has been studying coronaviruses for decades. In March 2020, he and his team published a preliminary report on potential therapeutic value of a new antiviral drug.
The coronavirus disease 2019 (COVID-19) pandemic, caused by the SARS-CoV-2 virus, has swept through the entire world, causing thousands of deaths and life-altering changes in our communities. Within the UNC School of Medicine research community of 28 basic science and clinical departments and more than 50 centers, institutes, programs, and initiatives, many researchers are working tirelessly to provide knowledge that can impact the current COVID-19 pandemic and future pandemics.
“UNC SOM is home to many world-renowned experts on infectious disease and virology,” said Blossom Damania, Boshamer Distinguished Professor and Vice Dean for Research at the UNC School of Medicine. “We are very appreciative of their collective ongoing clinical efforts and discovery research studies focused on understanding the biology, transmission, and treatment of SARS-CoV-2 and COVID-19. We are extremely grateful to the many clinicians that are working with patients on the frontline of this epidemic.”
Discovery and Diagnostic Research
Ralph Baric’s primary appointment is as the William R. Kenan Jr. Distinguished Professor at the UNC Gillings School of Public Health, and he holds a joint appointment as professor in the UNC Department of Microbiology and Immunology at the UNC School of Medicine. He is also a member of the Lineberger Comprehensive Cancer Center. Much of his research is focused on coronaviruses, and the lab is currently working on many aspects of SARS-CoV-2 including model development, mechanistic biology, and identification of potential antivirals and vaccine formulations. Because Baric is a renowned expert on coronaviruses, he has served on panels and appeared on many media outlets and public COVID-19 forums. In March, he lead a research team that published a preliminary report in bioRxiv that highlights the potential therapeutic value of a new antiviral, NHC/EIDD-2801, a compound that has shown to inhibit viral replication in preclinical trials of SARS-VoV-2.
Craig Cameron, Jeffrey Houpt Distinguished Professor and Chair of the Department of Microbiology and Immunology, and Jamie Arnold, research associate professor in the UNC Department of Cell Biology and Physiology, has partnered with Riboscience, LLC to screen their library of nucleotide analogues to identify those with efficacy against the SARS CoV-2 replicase, the RNA-dependent RNA-polymerase needed for multiplication of all RNA viruses. SARS CoV-2 is no different, and there is already evidence that its replicase represents an attractive target for development of antiviral therapeutics. Remdesivir, a nucleotide analog developed by Gilead Sciences to treat Ebola virus infection, is now known to inhibit SARS CoV-2 replicase. Also contributing to this effort is Robert Kirchdoerfer of the University of Wisconsin. Worth noting, nucleotide analogues as a class of antiviral agents have great potential to exhibit broad-spectrum activity, so this effort may have benefit beyond the current COVID-19 pandemic.
Aravinda de Silva, professor, and Prem Lakshmanane, research assistant professor, in the Department of Microbiology and Immunology, are experts in the area of mosquito-borne flavivirus and dengue virus vaccines and diagnostics. They are applying this broad-based knowledge of virology and human immunology to develop assays for specific detection of SARS-CoV-2 IgG and IgM antibodies. Furthermore, de Silva is working with Baric’s group to characterize vaccine responses.
Dirk Dittmer is a professor in the Department of Microbiology and Immunology, director of the UNC Viral Genomics Core, and director of the Virology and Global Oncology Programs at Lineberger. Dittmer and the Viral Genomics Core are setting up high-throughput, high-sensitivity COVID-19 viral load assays to augment hospital operations and to support clinical trials and pre-clinical studies. In addition, they are implementing next generation sequencing assays to characterize COVID-19 strains and other infectious agents in clinical research studies. Members of the laboratory of Blossom Damania, Professor of Microbiology and Immunology, are also involved in these efforts. Dittmer is also working with Melissa Miller, William Fischer, Subhashini Sellers, Ralph Baric and other faculty in the School of Medicine and Gillings School of Public Health.
J. Victor Garcia-Martinez, professor in the division of infectious diseases, and Angela Wahl, assistant professor in the division, are developing novel animal models of SARS-CoV-2 with Ralph Baric to further COVID-19 research. A recent Nature Biotechnology paper describes how Wahl and Garcia-Martinez previously developed a humanized mouse in collaboration with Baric for the in vivo testing of Middle East respiratory syndrome (MERS) coronavirus and other respiratory pathogens.
Mark Heise, professor in the Departments of Genetics and Microbiology and Immunology and Lineberger member, is working to develop mouse models of SARS-CoV-2 or testing of antivirals and vaccines. Heise has previously worked to develop mice receptive to MERS and SARS and works collaboratively with Baric.
Melissa Miller, is a professor in the Department of Pathology and Laboratory Medicine and Director of both the Clinical Molecular Microbiology Laboratory and the Clinical Microbiology Laboratory at the UNC Medical Center. In February, Miller and her team created a high-quality COVID-19 diagnostic test based on the World Health Organization assay which is now used for UNC Health patients, significantly increasing our ability to diagnose patients across North Carolina.
Nathanial Moorman is an associate professor in the Department of Microbiology and Immunology and Lineberger member. Moorman is using his expertise to screen for new antiviral agents against SARS-CoV-2 in partnership with Baric and Heise. This is also a collaboration with the UNC Eshelman School of Pharmacy.
Bryan Roth is the Michael Hooker Distinguished Professor in the Department of Pharmacology, has an appointment at Eshelman, and is the project director of the NIMH Psychoactive Drug Screening Program. Roth and his team are profiling candidate drugs to determine mechanism(s) of action that may contribute to therapeutic activity for COVID-19, and are also beginning screens of approved medications to determine if they might inhibit viral interactions with host receptors. The goal of his efforts is to discover medications that are already approved for human-use as potential therapeutics for COVID-19.
Ron Swanstrom is the Charles P. Postelle, Jr. Distinguished Professor of Biochemistry with a joint appointment in the Department of Microbiology and Immunology, and is the director of the UNC Center for AIDS Research. In collaboration with Baric’s team, Swanstrom tested a candidate therapeutic NHC/EIDD-2801: a ribonucleoside with broad-spectrum antiviral activity that works by inducing mutations in the viral genome.
Many researchers are also involved in clinical studies related to COVID-19.
Ross Boyce is an assistant professor in the division of infectious diseases in the Department of Medicine with a research focus on studying healthcare workers within the scope of COVID-19 as the pandemic progresses. Boyce is also working with Allison Aiello, professor of epidemiology, Jonathan Juliano, professor of medicine in the division of infectious diseases, Raquel Reyes, assistant professor of medicine in the division of hospital medicine, and Emily Ciccone, instructor in the division of infectious diseases.
Jessica Lin is also an assistant professor in the division of infectious diseases. Lin is working with David Wohl, Jonathan Juliano, and other researchers to launch a trial that asks whether treating individuals with mild to moderate symptoms who test positive for COVID-19 can prevent them from getting worse and needing to go into the hospital, and at the same time, also prevent spread to their household members. This “Treatment as Prevention” strategy has proven important in the public health response to HIV and may apply to the COVID-19 pandemic.
Subhashini Sellers and William Fischer are both assistant professors in the division of pulmonary diseases and critical care medicine in the Department of Medicine. Using their expertise in respiratory pathogens, Sellers and Fischer are both working with Dittmer in testing of COVID-19 samples. The team has worked together previously and has published on respiratory viral burden in persons with HIV, a study that demonstrated the sensitivity of next-generation sequencing for testing of all viruses including coronavirus. Fischer was also involved in the Ebola crisis in 2014-2016, and contributed to an article with David Wohl in the New England Journal of Medicine about disparities in patient care of Ebola virus disease, and has helped launched an international observational study of people hospitalized with COVID-19.
David Wohl, professor of medicine, and Natalie Bowman, assistant professor of medicine, are using their extensive knowledge of viral infections, epidemiology, and critical care medicine to track COVID-19 patients in the hospital and local community to help reduce the spread of SARS-CoV-2 infection as much as possible. David Wohl is also leading the UNC Respiratory Diagnostic units, and along with collaborator Joseph Eron, professor of medicine and chief of the division of infectious diseases, are members of the leadership of the AIDS Clinical Trials Group (ACTG), a multi-center, randomized trial that will test therapeutics (hydrochloroquine plus azithromycin) for early COVID-19.
Several of our School of Medicine centers are also involved in COVID-19 work. These include the HIV Cure Center and the Marsico Lung Institute. The HIV Cure Center is focused on finding a cure for HIV/AIDS. Numerous investigators are using their virology backgrounds and technical expertise to help accelerate research and testing of COVID-19 samples. For example, David Margolis, professor of medicine, microbiology and immunology, and epidemiology and director of the HIV Cure Center, is planning clinical trials to treat COVID-19 patients, with help from several colleagues including Edward Browne and Luther Bartelt, assistant professors of medicine.
Researchers within the Marsico Lung Institute / UNC Cystic Fibrosis Center are dedicated to finding a cure for cystic fibrosis and lung disease, and members have wide-ranging skills and interest from ion transport physiology to mucus secretion, and gene-targeted murine models. Investigators in this institute are working as a team to map the entry sites for SARS-CoV-2 in the respiratory tract and explore the risk / benefit aspects of drugs commonly used to treat respiratory disease for COVID-19. A number of investigators are embarking on preclinical studies to identify biomarkers that will predict the trajectory of COVID-19 lung disease and novel therapeutic strategies to treat patients. These studies involve Richard Boucher, director of the Marsico Lung Institute and the James C. Moeser Eminent Distinguished Professor of Medicine, Scott Randell, associate professor in the Department of Cell Biology and Physiology, Wanda O’Neal, associate professor of medicine and director of the Molecular Biology Core Laboratory, Matt Wolfgang, associate professor in the Department of Microbiology and Immunology, Ray Pickles, associate professor in the Department of Microbiology and Immunology, Brian Button, associate professor of biochemistry and biophysics with joint appointment in the Department of Medicine and the UNC-NC State Joint Department of Biomedical Engineering, Charles Esther, professor in the UNC Department of Pediatrics, Alessandra Livraghi-Butrico, assistant professor in the Department of Medicine, Mehmet Kesimer, associate professor in the Department of Pathology and Laboratory Medicine, Claire Doerschuk, professor in the Departments of Medicine and Pathology and Laboratory Medicine, Rob Hagan, clinical instructor in the Department of Medicine, Jason Mock, assistant professor of medicine and Christine Vigeland, clinical instructor in the Department of Medicine.
All these faculty are members of the UNC Institute for Global Health and Infectious Diseases, which fosters collaborative research to solve global health problems, reduce the burden of disease, and cultivate the next generation of global health leaders. Together these teams are working to understand SARS-CoV-2 and help find a cure to end the COVID-19 pandemic.
Finally, NC TraCS has been involved in supporting several COVID-19 clinical research projects in the school of medicine, including prophylactic trials on healthcare workers who are working with patients on the frontline of the epidemic. NC TraCS is also working with other CTSAs across the country to develop a database for COVID-19 patients.
October 22, 2020