Synergistic mechanism of 8P9R enhancing the antiviral activity of arbidol. a 8P9R could enhance the antiviral activity of arbidol against SARS-CoV-2 in Vero-E6 cells ( n = 5). Virus infected cells at the presence of the indicated concentrations of arbidol (Ar) or Ar+8P9R (1.6 μg ml −1 ) or Ar+8P9R (3.1 μg ml −1 ). b 8P9R could significantly enhance the antiviral activity of arbidol when arbidol alone did not show antiviral activity ( n = 4). SARS-CoV-2 was treated by the indicated Ar-0.2 (0.2 μg m l −1 ), 8P9R-3.1 (3.1 μg ml −1 ), Ar+8P9R, or PBS (Mock). P value was compared with Ar+8P9R. c SARS-CoV-2 (10 6 PFU ml −1 ) were treated by 25 μg ml −1 arbidol, or 8P9R ( n = 3). Then virus was serially diluted to detect the viral titer by plaque assay. d SARS-CoV-2 was treated at the indicated time of post infection by the indicated drugs ( n = 3). Viral titers ( a , b and d ) were measured by RT-qPCR at 24 h post infection. Relative RNA copy was normalized to MOCK. Data in ( a – d ) are presented as mean ± SD from 3–5 independent experiments. P values in ( b – d ) were calculated by two-tailed student t test when compared with mock. e Spike-ACE2 mediated cell-cell fusion could be blocked by arbidol and endosomal acidification inhibitors (bafilomycin A1 and 8P9R). The 293T cells expressed ACE2 or spike+GFP were co-cultured at the presence of indicated 8P9R (125 or 25 μg/ml), arbidol (50 or 25 μg ml −1 ) or bafilomycin A1 (BA1, 50 nM). 8P9R (25 μg ml −1 ) and arbidol (25 μg ml −1 ) did not block cell fusion, of which the fused cells were (2–10)-fold bigger than the non-fused cells. The 293T-GFP cells without spike (-Spike) served as the negative control of cell-cell fusion. Scale bar = 100 μm. The representative pictures were taken at 8 h after co-culture. Experiments were repeated three times independently. Source data are provided as a Source Data file.