Commonly prescribed antidepressants may be associated with protection against severe COVID-19. The mechanism of their action in this context, however, remains unknown. Here, I investigated the effect of an antidepressant drug fluvoxamine on membrane trafficking of the SARS-CoV-2 spike protein and its cell host receptor ACE2 in HEK293T cells. A sub-therapeutic concentration (80 nM) of fluvoxamine rapidly upregulated fluid-phase endocytosis, resulting in enhanced accumulation of the spike-ACE2 complex in enlarged early endosomes. Diversion of endosomal trafficking provides a simple cell biological mechanism consistent with the protective effect of antidepressants against COVID-19, highlighting their therapeutic and prophylactic potential.
【저자키워드】 COVID-19, Drug repurposing, SARS-CoV-2, antidepressants, endocytosis, 【초록키워드】 ACE2, severe COVID-19, Prophylactic, Spike protein, therapeutic, membrane, mechanism, protective effect, Concentration, Endosomes, host receptor, complex, diversion, HEK293T cells, endosomal trafficking, Cell, resulting, investigated, provide, upregulated, highlighting, the SARS-CoV-2, 【제목키워드】 spike, protection, fluvoxamine, antidepressant, Potential,