The outbreak of SARS-CoV-2 caused huge suffering and economic losses to human beings. There is an urgent need for small animal models that can reproduce SARS-CoV-2 infection in order to quickly evaluate medical measures. When scientists began to study this dangerous new disease in January this year, their eyes were focused on ACE2, which is a protein on the surface of various cells in the human body. SARS-CoV-2 is a new type of coronavirus that can cause COVID-19. It binds to the ACE2 receptor and uses it to enter cells, initiate growth and cause infection. However, it was discovered that SARS-CoV-2 cannot use the mouse version of the viral receptor ACE2.
Ralph Barrick's laboratory, a virologist at the University of North Carolina at Chapel Hill, uses their expertise because it has the ability to build mouse models for SARS-CoV, MERS-CoV and other coronaviruses History. SARS-CoV-2 has been implemented. Modified to use mouse ACE2 receptor.
In August 2020, Baric and his team modified two amino acid positions in the SARS-CoV-2 virus genome to construct a mouse-adapted virus (mouse-adapted virus) that can infect standard experimental mice. Achieved SARS-CoV-2 virus that can infect mice after mutation. The new COVID-19 mouse model developed from now on will reproduce many of the characteristics of the human disease and help advance COVID-19 vaccine candidates and antiviral drugs into clinical trials.
Currently, in a new study, Baric's team has screened a series of new SARS-CoV-2 virus variants that have evolved in vivo to match mice. They called it SARS-CoV-2MA10. This virus variant can reproduce multiple aspects of the severe COVID-19 disease in standard laboratory mice. For example, SARS-CoV-2MA10 showed a dose- and age-related increase in pathogenicity in BALB/c mice. .. The relevant research results were published online in Cell on September 23, 2020, with the title "Acute Lung Injury (ALI) and Mortality Caused by SARS-CoV-2 Adapted to AMouse in Standard Laboratory Mice".
SARS-CoV-2 model shows the morbidity and mortality of COVID-19 disease, as well as the genetic characteristics of the host, age, cell direction, increased Th1 cytokines, surfactant expression, and lungs. The increase in internal function loss is related to the pathological features of acute lung injury (acute lung injury, ALI) and acute respiratory distress syndrome (acute respiratory distress syndrome, ARDS).
"This SARS-CoV-2 model can quickly utilize existing mouse resources to play a role in host genetic characteristics, basic molecular mechanisms controlling the development of SARS-CoV-2, and disease severity. You can reveal the protective effects associated with it. Pathogenic immune response. This model provides a powerful platform for studying ALI and ARDS, using standard laboratory mice for vaccines and antiviral treatments in people including the most vulnerable (ie, the elderly). It is expected to be evaluated.