Bestion_2022_Viruses_14_132

Reference

Title : GNS561 Exhibits Potent Antiviral Activity against SARS-CoV-2 through Autophagy Inhibition - Bestion_2022_Viruses_14_132
Author(s) : Bestion E , Zandi K , Belouzard S , Andreani J , Lepidi H , Novello M , Rouquairol C , Baudoin JP , Rachid M , La Scola B , Mege JL , Dubuisson J , Schinazi RF , Mezouar S , Halfon P
Ref : Viruses , 14 :132 , 2022
Abstract :

Since December 2019, SARS-CoV-2 has spread quickly worldwide, leading to more than 280 million confirmed cases, including over 5,000,000 deaths. Interestingly, coronaviruses were found to subvert and hijack autophagic process to allow their viral replication. Autophagy-modulating compounds thus rapidly emerged as an attractive strategy to fight SARS-CoV-2 infection, including the well-known chloroquine (CQ). Here, we investigated the antiviral activity and associated mechanism of GNS561/Ezurpimtrostat, a small lysosomotropic molecule inhibitor of late-stage autophagy. Interestingly, GNS561 exhibited antiviral activity of 6-40 nM depending on the viral strain considered, currently positioning it as the most powerful molecule investigated in SARS-CoV-2 infection. We then showed that GNS561 was located in lysosome-associated-membrane-protein-2-positive (LAMP2-positive) lysosomes, together with SARS-CoV-2. Moreover, GNS561 increased LC3-II spot size and caused the accumulation of autophagic vacuoles and the presence of multilamellar bodies, suggesting that GNS561 disrupted the autophagy mechanism. To confirm our findings, we used the K18-hACE2 mouse model and highlighted that GNS561 treatment led to a decline in SARS-CoV-2 virions in the lungs associated with a disruption of the autophagy pathway. Overall, our study highlights GNS561 as a powerful drug in the treatment of SARS-CoV-2 infection and supports the hypothesis that autophagy blockers could be an alternative strategy for COVID-19.

PubMedSearch : Bestion_2022_Viruses_14_132
PubMedID: 35062337

Related information

Inhibitor Ezurpimtrostat

Citations formats

Bestion E, Zandi K, Belouzard S, Andreani J, Lepidi H, Novello M, Rouquairol C, Baudoin JP, Rachid M, La Scola B, Mege JL, Dubuisson J, Schinazi RF, Mezouar S, Halfon P (2022)
GNS561 Exhibits Potent Antiviral Activity against SARS-CoV-2 through Autophagy Inhibition
Viruses 14 :132

Bestion E, Zandi K, Belouzard S, Andreani J, Lepidi H, Novello M, Rouquairol C, Baudoin JP, Rachid M, La Scola B, Mege JL, Dubuisson J, Schinazi RF, Mezouar S, Halfon P (2022)
Viruses 14 :132