The SARS-CoV-2 cytopathic effect is blocked with autophagy modulators.

BioRxiv : the Preprint Server for Biology
Kirill GorshkovWei Zheng

Abstract

SARS-CoV-02 is a new type of coronavirus capable of rapid transmission and causing severe clinical symptoms; much of which has unknown biological etiology. It has prompted researchers to rapidly mobilize their efforts towards identifying and developing anti-viral therapeutics and vaccines. Discovering and understanding the virus' pathways of infection, host-protein interactions, and cytopathic effects will greatly aid in the design of new therapeutics to treat COVID-19. While it is known that chloroquine and hydroxychloroquine, extensively explored as clinical agents for COVID-19, have multiple cellular effects including inhibiting autophagy, there are also dose-limiting toxicities in patients that make clearly establishing their potential mechanisms-of-action problematic. Therefore, we evaluated a range of other autophagy modulators to identify an alternative autophagy-based drug repurposing opportunity. In this work, we found that 6 of these compounds blocked the cytopathic effect of SARS-CoV-2 in Vero-E6 cells with EC50 values ranging from 2.0 to 13 μM and selectivity indices ranging from 1.5 to >10-fold. Immunofluorescence staining for LC3B and LysoTracker dye staining assays in several cell lines indicated their potency an...Continue Reading

Citations

Jan 14, 2021·The Biochemical Journal·George M Burslem
Feb 13, 2021·Nutrients·Marina Vogel-GonzálezRobert Güerri-Fernández
Oct 15, 2020·The EMBO Journal·Julian BuchrieserOlivier Schwartz
Mar 11, 2021·Bioorganic & Medicinal Chemistry Letters·Khalida ShamimWenwei Huang
May 1, 2021·International Journal of Molecular Sciences·Gustavo José da Silva PereiraClaudia Bincoletto
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