iScience
Volume 24, Issue 12, 17 December 2021, 103412
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Article
Oral Hsp90 inhibitor SNX-5422 attenuates SARS-CoV-2 replication and dampens inflammation in airway cells

https://doi.org/10.1016/j.isci.2021.103412Get rights and content
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open access

Highlights

  • SNX-5422 inhibits SARS-CoV-2 replication in vitro at a high selectivity index

  • Transcriptomic profile of human airway epithelial cells treated with SNX-5422

  • SNX-5422 dampens proinflammatory pathways associated with poor COVID outcomes

  • SNX-5422 targets host factors crucial for SARS-CoV-2 replication

Summary

Currently available SARS-CoV-2 therapeutics are targeted toward moderately to severely ill patients and require intravenous infusions, with limited options for exposed or infected patients with no or mild symptoms. Although vaccines have demonstrated protective efficacy, vaccine hesitancy and logistical distribution challenges will delay their ability to end the pandemic. Hence, there is a need for rapidly translatable, easy-to-administer-therapeutics that can prevent SARS-CoV-2 disease progression, when administered in the early stages of infection. We demonstrate that an orally bioavailable Hsp90 inhibitor, SNX-5422, currently in clinical trials as an anti-cancer therapeutic, inhibits SARS-CoV-2 replication in vitro at a high selectivity index. SNX-5422 treatment of human primary airway epithelial cells dampened expression of inflammatory pathways previously associated with poor SARS-CoV-2 disease outcomes. In addition, SNX-5422 interrupted expression of host factors demonstrated to be crucial for SARS-CoV-2 replication. Development of SNX-5422 as SARS-CoV-2-early-therapy will dampen disease severity, resulting in better clinical outcomes and reduced hospitalizations.

Subject areas

Therapeutics
Virology

Data and code availability

  • The raw and processed RNA-seq data discussed in this publication have been deposited in NCBI's Gene Expression Omnibus (GEO) and are publicly available as of the date of publication. Accession numbers are listed in the key resources table.

  • This paper does not report original code.

  • Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

Cited by (0)

7

Present address: Computational Biology and Bioinformatics, Duke University School of Medicine, Durham, NC 27710, USA

8

Present address: Department of Pediatrics, Weill Cornell Medicine, New York, NY 10021, USA

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Lead contact