GVN Center and Member Spotlight

Zhengli Shi
Director, Center for Emerging Infectious Diseases of the Wuhan Institute of Virology, China
Director, GVN Center of Excellence

What are you and your institution currently working on regarding COVID-19?

Our institute has non-primate and mouse models for testing antiviral drugs or monoclonal antibodies against SARS-CoV-2. We are trying to develop the animal models which simulate the severe illness from COVID-19. This will enable us to understand how the pathogenesis developed in animals.

Please discuss the origins, isolation, evolution and cross-species-transmission of your bat coronavirus research.

From the beginning of this century, three coronaviruses (CoVs) have caused severe human respiratory diseases, including severe respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and corona virus disease 2019 (COVID-19), which emerged in 2002-2003, 2012 and 2019-2020, respectively. SARS-CoV and SARS-CoV-2 belong to SARAS-related CoV, MERS-CoV-2 belongs to MERS-related CoV. All of them belong to Coronaviridae family, Betacoronavirus genus. SARS-CoV is believed to be transmitted from civets in wet market and originated from horseshoe bats. MERS-CoV is transmitted by dromedary camels and originally came from bats. However, the origin of SARS-CoV-2 remains unclear although closely-related CoVs were discovered in bats and pangolins. Discovery of closely-related CoVs in bats indicates that bats could be natural reservoirs of these viruses. How and when the bat CoVs cross species barriers to infect humans are largely understudied. In the past 15 years, we have focused on the distribution and genetic diversity of bat coronaviruses in China, particularly SARS-related-CoVs and MERS-related CoVs. By using psudovirus or virus isolation, we have demonstrated that some bat coronaviruses utilize the same receptor with human coronaviruses (i.e., ACE2 for SARS-CoV; DPP4 for MERS-CoV). Our results indicate that these bat coronaviruses have potential of interspecies transmission to humans. Our work highlights the requirement of preparedness for future emerging coronaviruses.

Professional summary

Dr. Zhengli Shi’s laboratory focuses on pathogen investigation of bat-borne viruses, especially emerging coronaviruses with potential risk of interspecies transmission. In a 14-year study of tracing the origin of SARS since 2004, her team has isolated bat coronaviruses that are highly similar to SARS-CoV and use the same receptor, and discovered a natural gene pool of SARS-CoV in bats. These findings provided solid evidence for the bat origin of SARS-CoV (Li, W., et al., Bats are Natural Reservoirs of SARS-Like Coronaviruses. Science, 2005, 310: 676-679; Ge, X.Y., et al., Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor, Nature, 2013, 503: 535-538; Hu, B., et al., Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus, PLoS Pathog, 2017, 13: e1006698). Through long-term and extensive surveillance, her group has depicted the profile of distribution, genetic diversity and evolution of bat coronaviruses in China (Latinne, A., et al., Origin and cross-species transmission of bat coronaviruses in China. Nat Commun, 2020, 11: 4235) and characterized groups of bat coronaviruses with interspecies transmission risk (Yang, X.L., et al., Isolation and Characterization of a Novel Bat Coronavirus Closely Related to the Direct Progenitor of Severe Acute Respiratory Syndrome Coronavirus. J Virol, 2016, 90: 3253-3256; Hu, B., et al., PLoS Pathog, 2017; Luo, C.M., et al., Discovery of novel bat coronaviruses in South China that use the same receptor as Middle East respiratory syndrome coronavirus. J Virol, 2018, 92: e00116-18). Her group also demonstrated that the Swine Acute Diarrhea Syndrome (SADS) that emerged in 2016-2017 was caused by a bat HKU2-related coronavirus, giving the first direct evidence of bat coronavirus spillover to livestock (Zhou, P., et al., Fatal swine acute diarrhea syndrome caused by an HKU2-related coronavirus of bat origin. Nature, 2018, 556: 255-258). In addition to coronaviruses, Dr. Shi has discovered and characterized a great diversity of other novel bat viruses, some of which may have potential of spillover to humans such as a novel genus of filovirus (Yang, X.L., et al., Genetically diverse filoviruses in Rousettus and Eonycteris spp. bats, China, 2009 and 2015. Emerg Infect Dis, 2017, 23: 482-486; Yang, X.L., et al., Characterization of a filovirus (Měnglà virus) from Rousettus bats in China. Nat Microbiol, 2019, 4: 390-395).

Recently, soon after COVID-19 emerged, Dr. Shi’s team immediately isolated and characterized its causative agent, SARS-CoV-2, and suggested its potential bat origin (Zhou, P., et al., A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, 2020, 579: 270-273). They also established the transgenic human ACE2 mouse model for SARS-CoV-2 within a short time (Jiang, R.D., et al., Pathogenesis of SARS-CoV-2 in transgenic mice expressing human angiotensin-converting enzyme 2. Cell, 2020, 182: 50-58). These works have laid the essential foundation for all basic studies and countermeasure development of SARS-CoV-2, providing powerful tools for the combat against COVID-19.