Two Michigan State University scientists—Yong-Hui Zheng and Dohun Pyeon—are leading fundamental COVID-19 research at MSU.

MMG graduate students Morgan Collins (left), Ifeanyichukwu Eke (center) and Professor Zheng preparing lentiviruses pseudotyped with SARS-CoV-2 spike proteins to study how these COVID-19-causing viruses infect human lung cells. Photo: Harley J. Seeley

“In our lab, we are working on the fundamental biology of the virus,” said Zheng, a professor in the Department of Microbiology and Molecular Genetics (MMG) in the MSU College of Natural Science. “No matter what research you want to do, you need to first understand the virus.”

For more than 20 years, Zheng has focused on HIV and, more recently, began working with influenza and Ebola viruses.

“HIV, influenza, Ebola and COVID-19 all have one thing in common,” Zheng said. “They contain a ‘spike’ protein—sometimes called the S protein—which is critical in interacting with the cell surface to initiate infection.

“Our lab had already been working with spike proteins,” Zheng added. “Because the pathway in coronavirus is very similar, our previous work can be applied very quickly and easily to our COVID-19 work.”

Some of the coronavirus work on campus can be carried out only in Biosafety Level 3, or BSL-3, containment space—the highest containment level certified by the CDC lab. While MSU is developing new BSL-3 research space for this purpose, the main task in Zheng’s lab is to “divide up the system” so the research can then be done in other MSU labs that have a lower containment level certification.

MMG Associate Professor Dohun Pyeon (center); Danielle Hohman, a senior majoring in genomics and molecular genetics (left); and professional aide Lexi Vu, discuss new data from their COVID-19 work. Photo: Harley J. Seeley

“When we divide up a system, even though it can still replicate, it is no longer infectious to humans. In that case, you can have a broader number of labs that would be able to work on it,” Zheng said. “Simultaneously, we are studying how the virus enters the cell—the first step for the virus to start infection.”

“My fundamental interest is to understand how SARS-CoV-2 interacts with and hijacks the host cellular mechanism for entry, replication, and pathogenesis,” said Pyeon, an associate professor whose lab has focused on the human papillomavirus (HPV) and cancer development. “Our goal is to develop a neutralizing antibody that can be used almost immediately to develop therapeutics.”

To develop this neutralizing antibody, Pyeon’s lab is collaborating with Xuefei Huang, MSU Foundation Professor of chemistry.

SARS-CoV-2 structure

“Once the antibody is ready, we are going to test if the antibodies actually block virus infection in lung epithelial cells using SARS-CoV-2 pseudotyped virions,” Pyeon said. “This neutralizing antibody could be used as a therapeutic, injected directly into COVID-19 patients to stop virus infection.”

In May, Zheng and Bruce Uhal, professor of physiology, launched a Journal Club on COVID-19/SARS-CoV-2—a group of more than a dozen MSU scientists who gather weekly via Zoom to review publications and share their work in the area of coronavirus research.

“So many individuals have different areas of expertise, but they don’t know how to find collaborators,” Zheng said. “With this group, we can determine what each lab is doing so we can begin some collaborative projects.”

“Even if we successfully develop drugs and vaccines for a specific virus, we don’t know what other types of viruses will emerge in the future,” Pyeon said. “That is why persistent and continuous research in virology is critical for preparing for future outbreaks and pandemics.”

Note: This story was one of several featured in the recent issue of the MMG newsletter. To read more about other activities in the department, click here.

Banner image: This illustration, created at the Centers for Disease Control and Prevention, reveals ultrastructural morphology exhibited by the Covid-19 coronavirus (before 2019 novel coronavirus). Even if drugs and vaccines are successfully developed for a specific virus, it is unknown what other types of viruses will emerge in the future. That is why persistent and continuous research in virology is critical for preparing for future outbreaks and pandemics.

Story via the College of Natural Science