PT  - JOURNAL ARTICLE
AU  - Luca Mazzarella
AU  - Fabio Santoro
AU  - Roberto Ravasio
AU  - Paul E. Massa
AU  - Simona Rodighiero
AU  - Elena Gavilán
AU  - Mauro Romanenghi
AU  - Bruno Achutti Duso
AU  - Emanuele Bonetti
AU  - Rani Pallavi
AU  - Deborah Trastulli
AU  - Isabella Pallavicini
AU  - Claudia Gentile
AU  - Tommaso Leonardi
AU  - Sebastiano Pasqualato
AU  - Gabriele Buttinelli
AU  - Angela Di Martino
AU  - Giorgio Fedele
AU  - Ilaria Schiavoni
AU  - Paola Stefanelli
AU  - Giuseppe Meroni
AU  - Christian Steinkuhler
AU  - Gianluca Fossati
AU  - Saverio Minucci
AU  - Pier Giuseppe Pelicci
TI  - Inhibiting LSD1 suppresses coronavirus-induced inflammation but spares innate antiviral activity
AID  - 10.1101/2021.05.02.441948
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.05.02.441948
4099  - http://biorxiv.org/content/early/2021/05/03/2021.05.02.441948.short
4100  - http://biorxiv.org/content/early/2021/05/03/2021.05.02.441948.full
AB  - Tissue-resident macrophages exert critical but conflicting effects on the progression of coronavirus infections by secreting both anti-viral type I Interferons and tissue-damaging inflammatory cytokines. Steroids, the only class of host-targeting drugs approved for Covid19, indiscriminately suppress both responses, possibly impairing viral clearance, and provide limited clinical benefit. Here we set up a mouse in vitro co-culture system that reproduces the macrophage response to SARS-CoV2 seen in patients and allows quantitation of inflammatory and antiviral activities. We show that the NFKB-dependent inflammatory response can be selectively inhibited by ablating the lysine-demethylase LSD1, which additionally unleashed interferon-independent ISG activation and blocked viral egress through the lysosomal pathway. These results provide a rationale for repurposing LSD1 inhibitors, a class of drugs extensively studied in oncology, for Covid-19 treatment.One-Sentence Summary Targeting a chromatin-modifying enzyme in coronavirus infections curbs tissue-damage without affecting antiviral responseCompeting Interest StatementThe authors have declared no competing interest.