A study published in Nature (DOI: 10.1038/s41586-020-2312-y) investigated the pathogenicity of SARS-CoV-2 in hACE2 transgenic mice, which express human angiotensin-converting enzyme 2 (ACE2), the receptor for SARS-CoV. The researchers infected these mice with the SARS-CoV-2 strain HB-01 and observed weight loss, viral replication in the lungs, and histopathological changes such as interstitial pneumonia and macrophage accumulation. Viral antigens were detected in bronchial epithelial cells, macrophages, and alveolar epithelia, but not in wild-type mice. The study confirmed that SARS-CoV-2 can infect hACE2 mice, leading to significant weight loss and viral replication, and that the virus can be isolated from the lungs. The mice also developed specific IgG antibodies against the SARS-CoV-2 spike protein. Histopathological analysis revealed progressive lung damage, including thickened alveolar septa and inflammatory cell infiltration. The study demonstrated that SARS-CoV-2 uses human ACE2 as an entry receptor, similar to SARS-CoV. The findings support the use of hACE2 mice as a model for studying SARS-CoV-2 pathogenesis and evaluating antiviral therapies and vaccines. The study also highlights differences in pathogenicity between SARS-CoV-2 and SARS-CoV, with SARS-CoV-2 causing primarily interstitial pneumonia in mice, while SARS-CoV causes extrapulmonary damage. The results confirm that SARS-CoV-2 is the causative agent of COVID-19 and satisfy Koch's postulates, providing a valuable model for further research.A study published in Nature (DOI: 10.1038/s41586-020-2312-y) investigated the pathogenicity of SARS-CoV-2 in hACE2 transgenic mice, which express human angiotensin-converting enzyme 2 (ACE2), the receptor for SARS-CoV. The researchers infected these mice with the SARS-CoV-2 strain HB-01 and observed weight loss, viral replication in the lungs, and histopathological changes such as interstitial pneumonia and macrophage accumulation. Viral antigens were detected in bronchial epithelial cells, macrophages, and alveolar epithelia, but not in wild-type mice. The study confirmed that SARS-CoV-2 can infect hACE2 mice, leading to significant weight loss and viral replication, and that the virus can be isolated from the lungs. The mice also developed specific IgG antibodies against the SARS-CoV-2 spike protein. Histopathological analysis revealed progressive lung damage, including thickened alveolar septa and inflammatory cell infiltration. The study demonstrated that SARS-CoV-2 uses human ACE2 as an entry receptor, similar to SARS-CoV. The findings support the use of hACE2 mice as a model for studying SARS-CoV-2 pathogenesis and evaluating antiviral therapies and vaccines. The study also highlights differences in pathogenicity between SARS-CoV-2 and SARS-CoV, with SARS-CoV-2 causing primarily interstitial pneumonia in mice, while SARS-CoV causes extrapulmonary damage. The results confirm that SARS-CoV-2 is the causative agent of COVID-19 and satisfy Koch's postulates, providing a valuable model for further research.