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HGNC Genes

SARS-CoV-2 proteins

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

    Authors: Kirill Gorshkov; Catherine Z. Chen; Robert Bostwick; Lynn Rasmussen; Miao Xu; Manisha Pradhan; Bruce Nguyen Tran; Wei Zhu; Khalida Shamim; Wenwei Huang; Xin Hu; Min Shen; Carleen Klumpp-Thomas; Zina Itkin; Paul Shinn; Anton Simeonov; Sam Michael; Matthew D. Hall; Donald C. Lo; Wei Zheng

    doi:10.1101/2020.05.16.091520 Date: 2020-05-21 Source: bioRxiv

    SARS-CoV-2 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 MESHD. While it is known that chloroquine and hydroxychloroquine, extensively explored as clinical agents for COVID-19 MESHD, have multiple cellular effects including inhibiting autophagy, there are also dose-limiting toxicities MESHD 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 HGNC and LysoTracker dye staining assays in several cell lines indicated their potency and efficacy for inhibiting autophagy correlated with the measurements in the SARS-CoV-2 cytopathic effect assay. Our data suggest that autophagy pathways could be targeted to combat SARS-CoV-2 infections MESHD SARS-CoV-2 infections MESHD and become an important component of drug combination therapies to improve the treatment outcomes for COVID-19 MESHD.One Sentence Summary Blocking SARS-CoV-2 cytopathic effects with selective autophagy inhibitors underlying the clinical benefits of chloroquine and hydroxychloroquine.Competing Interest StatementThe authors have declared no competing interest.View Full Text

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MeSH Disease
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SARS-CoV-2 Proteins


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