Fluvoxamine’s anti-COVID-19 effects linked to its ability to suppress ceramide levels

Key Messages

A waxy fatty substance known as “ceramide” plays an essential role in the ability of SARS-CoV-2 to infect human cells. Low ceramide levels protect against infection, whereas high levels feed the infection process.

The key to suppressing ceramide production lies in blocking an enzyme called acid sphingomyelinase (ASM).

A number of well-established drugs are capable of blocking the ASM enzyme. These drugs are referred to as FIASMAs - short for “functional inhibitors of acid sphingomyelinase”.

The anti-depressant drug fluvoxamine is a member of the FIASMA class of drugs. According to this review article, this may provide an additional explanation for fluvoxamine’s anti-COVID-19 effects.

Molecular Psychiatry

Publication Date: October 4, 2021
Peer Reviewed: Yes
Publication Type: Review/Commentary/Letter
DOI: https://www.doi.org/10.1038/s41380-021-01309-5

The acid sphingomyelinase/ceramide system in COVID-19

Johannes Kornhuber, Nicolas Hoertel, Erich Gulbins

Abstract

Acid sphingomyelinase (ASM) cleaves sphingomyelin into the highly lipophilic ceramide, which forms large gel-like rafts/platforms in the plasma membrane. We showed that SARS-CoV-2 uses these platforms for cell entry. Lowering the amount of ceramide or ceramide blockade due to inhibitors of ASM, genetic downregulation of ASM, anti-ceramide antibodies or degradation by neutral ceramidase protected against infection with SARS-CoV-2. The addition of ceramide restored infection with SARS-CoV-2. Many clinically approved medications functionally inhibit ASM and are called FIASMAs (functional inhibitors of acid sphingomyelinase). The FIASMA fluvoxamine showed beneficial effects on COVID-19 in a randomized prospective study and a prospective open-label real-world study. Retrospective and observational studies showed favorable effects of FIASMA antidepressants including fluoxetine, and the FIASMA hydroxyzine on the course of COVID-19. The ASM/ceramide system provides a framework for a better understanding of the infection of cells by SARS-CoV-2 and the clinical, antiviral, and anti-inflammatory effects of functional inhibitors of ASM. This framework also supports the development of new drugs or the repurposing of “old” drugs against COVID-19.