a, Weight loss was recorded for 14 days. hACE2 mice (n = 7) and wild-type (WT) mice (n = 3) were experimentally challenged intranasally with SARS-CoV-2 HB-01, and mock-treated hACE2 (ACE2 + mock) mice (n = 3) were used as control. According to two-tailed Mann–Whitney U-test, the weight of HB-01-infected hACE2 mice (ACE2 + HB-01) displayed a significant decline compared with that of HB-01-infected wild-type mice (WT + HB-01) or mock-treated hACE2 mice (***P = 0.0005). b, To measure viral RNA, 12 mice were infected in each group. Three mice per group were killed, and their major organs (including testis in male mice) were collected for analysis of viral loads and virus titre at 1, 3, 5 and 7 dpi. The distribution of SARS-CoV-2 in the primary organs of HB-01-infected hACE2 mice was detected using RT–qPCR. c, Virus titres in the lungs were determined on Vero E6 cells. According to a two-tailed unpaired Welch’s t-test, viral titres in the lungs from HB-01-infected hACE2 mice (n = 3) showed a significant increase compared with those in HB-01-infected wild-type mice (n = 3) or mock-treated hACE2 mice (n = 3) at 1 (**P = 0.0053), 3 (**P = 0.0022) and 5 (**P = 0.0081) dpi. d, Virus isolated from the lungs of HB-01-infected hACE2 mice at 3 dpi was observed using electron microscopy. Scale bar, 200 nm. Data are representative of three independent experiments. e, The specific IgG against SARS-CoV-2 was detected from the sera of mice (HB-01-infected wild-type (n = 3) or hACE2 ( n =7) mice) at day 0 and 21 dpi by enzyme-linked immunosorbent assay (ELISA). OD450, optical density at 450 nm. Two-tailed unpaired Student’s t-test; not significant (NS), P = 0.2193; two-tailed unpaired Welch’s t-test, ***P = 3.11 × 10−6. Data in a–c, e are mean ± s.d.