Thanks to grants from the National Science Foundation’s Rapid Response Research program for priority project, two University of Rochester biologists received expedited federal funds to follow the interaction of coronavirus with proteins in human cells. In one study, Dragony Fu pursues the hypothesis COVID-19 protease cuts TRMT1, preventing the protein from modifying RNA as it normally does, and in turn, compromising RNA’s function in protein synthesis. Understanding this possible connection could serve as potential therapeutic targets for treatment of COVID-19 infection. Meanwhile, Jack Werren utilizes grant money, based on his expertise in evolutionary rate correlation, to identify proteins that may coevolve and interact with the ACE2 receptor on human cells. The hope is that this research as well can lead to useful pathways to help identify targets for therapeutic intervention.
Dragony Fu, assistant professor of biology and Jack Werren, the Nathaniel and Helen Wisch Professor of Biology team with others to hopefully leverage the expertise to research proteins in infections associated with COVID-19. The key goal of this basic research is to comprehend the biological mechanisms and proteins associated with SARS-CoV-2 infection leading to superior treatments and vaccines, reports the University of Rochester News Center.
The Links Connecting SARS-CoV & Proteins & RNA
This grant supports University of Rochester’s Fu and the collaboration with the French National Centre for Scientific Research to study why SARS-CoV-2 interacts with TRMT1 and how this interaction affects both the virus and human cells. The University of Rochester hypothesis via Professor Fu: COVID-19 protease cuts TRMT1, preventing the protein from modifying RNA as it normally does, and in turn, compromising RNA’s function in protein synthesis.
COVID-19 virus produces proteases, proteins that behave like scissors that server the virus’s own proteins into smaller, functional pieces: these are necessary for viral infection. Researchers at the University of California, San Francisco recently found that the maFu reports on this topic, “The central goal of our lab is to understand the functions of proteins that modify RNA.” He continued, “TRMT1 happens to be one of the main RNA modification proteins we study, so it was quite serendipitous that it is connected to the COVID-19 virus because we have already established tests to measure TRMT1 function in human cells.”
Leveraging molecular biology techniques, Fu and French collaborators will deliver the viral protease gene into human lung cells. Thereafter by employing antibodies to detect TRMT1 they seek to determine whether the protein is being severed by the viral protease. If affirmative, biochemical assays are utilized to analyze how the viral protease impacts TRMT1 function, RNA modification and protein synthesis. Fu summarized, “We will be able to use this knowledge to discover new connections between the virus and the host human cell.”
Why does it matter? In Fu’s own words, “These novel links could serve as potential therapeutic targets for treatment of COVID-19 infection.
Leveraging Known Methods to Explore Proteins & Enzyme Receptors
Meanwhile in the Werren lab, another team led by Werren will capitalize on funding to identify interactions between an enzyme receptor located on call surfaces—the Angiotensin-converting enzyme 2 (the virus binds to this receptor upon entry)—and other human proteins involved in health issues linked to COVID-19 infection. Using his expertise in evolutionary rate correlation, Werren expects to identify proteins that may coevolve and interact with the ACE2 receptor on human cells. Werren is using the ERC approach to determine protein interactions relevant to severe symptoms of the disease. Werren comments, “Our goal is to characterize these interactions further and quickly publish the findings, in case the information will be useful in identifying targets for therapeutic intervention,” Werren says.
Dragony Fu, assistant professor of biology
Jack Werren, PhD, the Nathaniel and Helen Wisch Professor of Biology team