A mouse-adapted model of SARS-CoV-2 to test COVID-19 countermeasures

Standard laboratory mice do not support infection with SARS-CoV-2 due to incompatibility of viral spike (S) protein to the murine ACE2. A recombinant SARS-CoV-2 was generated by a reverse genetics system, the receptor-binding domain (RBD) of whose S protein was modified to interact with murine ACE2 by referring the amino acid sequence of S proteins from other species of coronavirus that can infect to mice. The mouse-adapted virus (SARS-CoV-2 MA) replicates in the upper and lower airways of BALB/c mice, and the severity was stronger in aged animals than in young animals. Moreover, this mouse infection model was useful for the evaluation of antiviral drug efficacy such as interferon lambda-1a against viral infection.