In the history of coexisting with viruses, mankind has only defeated a handful of viruses such as smallpox and hepatitis C. There are still a large number of viruses that threaten human life and health. Mankind has no effective countermeasures. Major threats such as the new COVID-19, influenza virus, Ebola virus, Lassa virus and Zika virus are challenging the international public health system, and the scientific community and industry are also racing against them.
Overcoming emerging infectious diseases caused by viruses is the common aspiration of all mankind, and it is also the frontier of the scientific research community. However, the diversity of viruses and their rapid mutations pose a great challenge to virus research and drug development. To be proactive for the prevention and control of emerging infectious diseases, we should strengthen the virus surveillance and pandemic preparedness including development of broad-spectrum drugs and universal vaccines , Dr. Yi Shi and his team are aiming to overcome this challenge.
As early as when he set up his laboratory, Yi made a forward-looking layout around viral polymerase research. Viral polymerase is the protein machine that is responsible for the virus genome replication and transcription. The polymerase has common characteristics in different types of viruses, which provides a valuable start point for the development of broad-spectrum antiviral drugs.
Since 2016, Yi has spent more than three years in the research of viral polymerase. He found that the genome of the influenza virus has different conformations when bound with polymerase, which can regulate the working process of polymerase. Meanwhile, Yi led the team to study the functional and structural characterizations of arenavirus polymerase and the matrix Z protein. Yi has revealed the structural features of the arenavirus polymerases and how the Z protein inhibits the polymerase function. Otherwise, he has found a similar 3’RNA binding site in the polymerases from influenza virus, arenavirus and bunyavirus. Based on these findings, he led the team to find several new drug targets, providing a key direction for the subsequent development of new drugs.
After the outbreak of COVID-19, Yi and his team quickly made a series of novel findings on the functional and structural characteristics of polymerases from SARS-CoV-2 and clarified the way Favipiravir interacts with the coronavirus polymerase. Favipiravir is a broad-spectrum antiviral drug that can fight against a variety of RNA viruses. Many countries have used it to treat COVID-19. Yi called it "old drug with new use."
Regarding the future, Yi said that he will continue studying other important viruses such as ASFV. He is also working with other teams to explore unknown viruses in extreme environments such as glaciers and frozen soils and strive to expand the new boundaries of virology.
