Figure 1.

SARS-CoV-2 and apilimod both inhibit the immune system in a similar manner. (A) Scheme of the viral S protein indicating the functional domains and the two proteolytic activation sites S1/2 and S2′. Apilimod, an inhibitor of PIKfyve, interferes with the endo/lysosomal trafficking and can indirectly block the activation of proteases as shown for Cathepsin B and L. Apilimod thereby likely interferes with proteolytic activation of the S protein and prevents host cell invasion. (B) Both upon infection with SARS-CoV-2 and upon exposure to apilimod, antigen presenting cells (APC) express lower levels of surface MHC class II (HLA-DR; MHCII) and produce less type I interferons (INF-α/β).