Quercetin blocks Ebola Virus infection by counteracting the VP24 Interferon inhibitory function

Fanunza, Elisa
Distinto, Simona;Corona, Angela;Quartu, Marina;Maccioni, Elias;Horvat, Branka;Tramontano, Enzo


Ebola Virus (EBOV) is among the most devastating pathogens causing fatal hemorrhagic fever in humans. The 2013–2016 epidemics resulted in over 11000 deaths, while another outbreak is currently ongoing. Since there is no FDA-approved drug so far to fight EBOV infection, there is an urgent need to focus on drug discovery. Considering the tight correlation between the high EBOV virulence and its ability to suppress the type-I Interferon (IFN-I) system, identifying molecules targeting viral protein VP24, one of the main virulence determinants blocking IFN response, is a promising novel anti-EBOV therapy approach. Hence, in the effort of finding novel EBOV inhibitors, a screening of a small set of flavonoids was performed, showing that Quercetin and Wogonin can suppress the VP24 effect on IFN-I signaling inhibition. The mechanism of action of the most active compound, Quercetin, showing an IC50 value of 7.4 μM, was characterized to significantly restore the IFN-I signaling cascade, blocked by VP24, by directly interfering with the VP24 binding to karyopherin-α and thus restoring P-STAT1 nuclear transport and IFN genes transcription. Quercetin significantly blocked viral infection, specifically targeting EBOV VP24 anti-IFN-I function. Overall, Quercetin is the first identified inhibitor of the EBOV VP24 anti-IFN function, representing a molecule interacting with a viral binding site that is very promising for further drug development aiming to block EBOV infection at the early steps.
Esperti anonimi
Ebola virus; EBOV; VP24; IFN signaling; Drug development, luciferase assay; Flavonoids; Quercetin
Fanunza, Elisa; Iampietro, Mathieu; Distinto, Simona; Corona, Angela; Quartu, Marina; Maccioni, Elias; Horvat, Branka; Tramontano, Enzo
1.1 Articolo in rivista
1 Contributo su Rivista::1.1 Articolo in rivista
File in questo prodotto:
File Dimensione Formato  
2020 Fanunza Antimicrobial Agents and Chemotherapy-2020-Fanunza-AAC.00530-20.full.pdf

embargo fino al 09/11/2020

Tipologia: versione post-print
Dimensione 4.02 MB
Formato Adobe PDF
4.02 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Questionario e social

Condividi su:
Impostazioni cookie