Low-dose fluvoxamine modulates the cellular levels of the SARS-CoV-2 spike protein to protect against viral infection.

Key Messages

Antidepressants, including fluvoxamine, are a promising group of drugs that studies have indicated can protect against severe COVID-19.

The potential protective effect of fluvoxamine against severe COVID-19 has been linked to its effect on the immune response.

This study investigates the effect of low-dose fluvoxamine on SARS-CoV-2 and the levels of the spike receptor protein on human cells. Fluvoxamine may not only prevent severe COVID-19, but may also protect against SARS-CoV-2 infection by reducing the levels of the spike receptor protein.


Publication Date: June 15, 2021
Peer Reviewed: No
Publication Type: Original | Preclinical
DOI: https://www.doi.org/10.1101/2021.06.15.448391

Low-dose fluvoxamine modulates endocytic trafficking of SARS-CoV-2 spike protein: a potential mechanism for anti-COVID-19 protection by antidepressants

Oleg O Glebov


Commonly prescribed antidepressants may be associated with protection against severe COVID-19, with one drug (fluvoxamine) currently undergoing a Phase 3 clinical trial. The mechanism of their action, however, remains unknown. Here, I investigated the effect of 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 may provide a simple cell biological mechanism consistent with the protective effect of antidepressants against COVID-19, highlighting their therapeutic and prophylactic potential.