Fig. 4: Drug combination enhanced the antiviral activity against SARS-CoV-2 and SARS-CoV.

a Chloroquine (Chl) could significantly enhance the activity of arbidol against SARS-CoV-2 while arbidol alone (0.2 μg ml⁻¹, Ar-0.2) did not show antiviral activity (n = 4). SARS-CoV-2 was treated by the indicated Ar-0.2, Chl-3.1 (3.1 μg ml⁻¹), or Ar+Chl. P value was compared with Chl-3.1. b Chloroquine (Chl) could significantly enhance the activity of arbidol against SARS-CoV while arbidol alone (0.4 μg ml⁻¹, Ar-0.4) did not show antiviral activity (n = 4). SARS-CoV was treated by the indicated Ar-0.4, Chl-6.3 (6.3 μg ml⁻¹), or Ar+Chl. Viral RNA copies were measured at 24 h post infection in cell supernatants. The relative RNA copy was compared to mock treated virus. P value was compared with Chl-6.3. c The antiviral activity of indicated drugs or drug combinations against SARS-CoV in mice. Mice were intranasally inoculated with SARS-CoV (5 × 10³ PFU). 8P9R (intranasal 0.5 mg kg⁻¹, n = 8), arbidol (Ar, oral 30 mg kg⁻¹, n = 8), chloroquine (Chl, oral 40 mg kg⁻¹, n = 6), camostat (Cam, intranasal 0.3 mg kg⁻¹, n = 5), Ar+Chl (n = 6), Ar+Cam (n = 6), Chl+Cam (n = 6), Ar+Chl+Cam (n = 5) and mock (n = 12) were given to mice at 8 h post infection. Two more doses were given to mice in the following day. Viral loads in lung tissues were measured by plaque assay at day 2 post infection. d–e The antiviral activity of 8P9R (12.5 μg ml⁻¹), arbidol (12.5 μg ml⁻¹), and chloroquine (12.5 μg ml⁻¹) in Vero-E6 (d, n = 4) and Calu-3 (e, n = 3) cells. Viral RNA copies in cell supernatants were measured by RT-qPCR at 24 h post infection. Relative RNA copy was normalized to mock. f The antiviral activity of indicated drugs or drug combinations against SARS-CoV-2 in hamsters. Hamsters were intranasally inoculated with SARS-CoV-2 (5 × 10³ PFU). Mock (n = 9), 8P9R (intranasal 0.5 mg kg⁻¹, n = 4), Ar+Chl+Cam (n = 6), Chl+Cam (n = 6), Ar+Cam (3), Cam (intranasal 0.3 mg kg⁻¹, n = 5), Ar (oral 30 mg kg⁻¹, n = 3), and Chl (oral 40 mg kg⁻¹, n = 4) were given to hamsters at 8 h post infection. Two more doses were given to hamsters in the following day. Viral loads in lung tissues were measured by plaque assay at day 2 post infection. Data are presented as mean ± SD of independent biological samples. P values are calculated by two-tailed student t test when compared with mock. Source data are provided as a Source Data file.