מחקר מעבדה מגלה שמספר תרופות נוגדות דיכאון, כולל פלובוקסאמין, יכולות לדכא התפתחות זיהום ב-SARS-CoV-2.

ממצאים עיקריים

מחקר מעבדה זה בחן את יכולתן של תרופות נגד דיכאון, כולל פלובוקסאמין, במניעת הידבקות בנגיף SARS-CoV-2, והציג פעילות אנטי-ויראלית ישירה של פלובוקסאמין.

תאים שנחשפו ל-SARS-CoV-2 וטופלו באמצעות פלובוקסאמין בתוך 24 שעות, הציגו רמות נמוכות משמעותית של SARS-CoV-2 מתאים שנחשפו לנגיף ולא טופלו.

בנוסף, פלובוקסאמין לא הציגה השפעות רעליות על התאים שנבדקו.

bioRxiv

Publication Date: מרץ 23, 2021
Peer Reviewed: No
Publication Type: Original | Preclinical
DOI: https://www.doi.org/10.1101/2021.03.22.436379

Antidepressant and antipsychotic drugs reduce viral infection by SARS-CoV-2 and fluoxetine show antiviral activity against the novel variants in vitro

Senem Merve Fred, Suvi Kuivanen, Hasan Ugurlu, Plinio Cabrera Casarotto, Lev Levanov, Kalle Saksela, Olli Vapalahti, Eero Castrén

Abstract

Background and Purpose
Repurposing of currently available drugs is a valuable strategy to tackle the consequences of COVID-19. Recently, several studies have investigated the effect of psychoactive drugs on SARS-CoV-2 in cell culture models as well as in clinical practice. Our aim was to expand these studies and test some of these compounds against newly emerged variants.

Experimental Approach
Several antidepressant drugs and antipsychotic drugs with different primary mechanisms of action were tested in ACE2/TMPRSS2-expressing human embryonic kidney cells against the infection by SARS-CoV-2 spike protein-dependent pseudoviruses. Some of these compounds were also tested in human lung epithelial cell line, Calu-1, against the first wave (B.1) lineage of SARS-CoV-2 and the variants of concern, B.1.1.7 and B.1.351.

Key Results
Several clinically used antidepressants, including fluoxetine, citalopram, reboxetine, imipramine, as well as antipsychotic compounds chlorpromazine, flupenthixol, and pimozide inhibited the infection by pseudotyped viruses with minimal effects on cell viability. The antiviral action of several of these drugs was verified in Calu-1 cells against the (B.1) lineage of SARS-CoV-2. By contrast, the anticonvulsant carbamazepine, and novel antidepressants ketamine and its derivatives as well as MAO and phosphodiesterase inhibitors phenelzine and rolipram, respectively, showed no activity in the pseudovirus model. Furthermore, fluoxetine remained effective against pseudo viruses with N501Y, K417N, and E484K spike mutations, and the VoC-1 (B.1.1.7) and VoC-2 (B.1.351) variants of SARS-CoV-2.

Conclusion and Implications
Our study confirms previous data and extends information on the repurposing of these drugs to counteract SARS-CoV-2 infection including different variants of concern.