C5 and factor D inhibition block complement activation induced by SARS-CoV-2 spike proteins. Flow cytometry demonstrated C5b-9 depositions induced by 20 µg/mL SARS-CoV-2 S1 (A) and S2 (C) were completely blocked in the presence of 1 µM factor D inhibitor (ACH145951) or 50 µg of anti-C5 antibody. C3c depositions induced by 20 µg/mL S1 (B) and S2 (D) were significantly reduced by factor D inhibitor but not by anti-C5 antibody. (E) A representative flow cytometry analysis demonstrated that 1 µM factor D inhibitor (dark blue curve) completely blocked the C5b-9 (left panel) and C3c deposition (right panel) triggered by 20 µg/mL S1 proteins (red curve). C5 inhibition with 50 µg of anti-C5 antibody (cyan curve) prevented S1-induced C5b-9 deposition, but not C3c accumulation. All experiments were repeated 3 times. Unpaired Student t test P values indicate statistical significance (*P < .05, **P < .01).