Possible role of ABCB1 in lysosomal accumulation of azithromycin in COVID‐19 therapy

Scherrmann, Jean‐Michel

The antiviral use of azithromycin in COVID‐19 was recently reported by Damle et al. Its combination with hydroxychloroquine did not aim at preventing bacterial super‐infection as often believed, but at benefiting from their common lysosomotropic properties which buffer the acidic conditions (pH 4‐5) of the endolysosomal lumen where SARS‐CoV‐2 transits following its ACE‐2 receptor‐mediated endocytosis. These two powerful cationic and amphiphilic drugs increase up to neutrality the intravesicular pH causing disorders in lysosomal functions such as enzyme inhibitions involved in the virus replication cycle. We recently hypothesized that the ATP‐binding cassette ABCB1 (P‐glycoprotein) could be involved in this reported synergistic effect.