Salicylanilides Reduce SARS-CoV-2 Replication and Suppress Induction of Inflammatory Cytokines in a Rodent Model

Steven Blake, Namir Shaabani, Lisa M. Eubanks, Junki Maruyama, John T. Manning, Nathan Beutler, Slobodan Paessler, Henry Ji, John R. Teijaro, Kim D. Janda

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

SARS-CoV-2 virus has recently given rise to the current COVID-19 pandemic where infected individuals can range from being asymptomatic, yet highly contagious, to dying from acute respiratory distress syndrome. Although the world has mobilized to create antiviral vaccines and therapeutics to combat the scourge, their long-term efficacy remains in question especially with the emergence of new variants. In this work, we exploit a class of compounds that has previously shown success against various viruses. A salicylanilide library was first screened in a SARS-CoV-2 activity assay in Vero cells. The most efficacious derivative was further evaluated in a prophylactic mouse model of SARS-CoV-2 infection unveiling a salicylanilide that can reduce viral loads, modulate key cytokines, and mitigate severe weight loss involved in COVID-19 infections. The combination of anti-SARS-CoV-2 activity, cytokine inhibitory activity, and a previously established favorable pharmacokinetic profile for the lead salicylanilide renders salicylanilides in general as promising therapeutics for COVID-19.

Original languageEnglish (US)
Pages (from-to)2229-2237
Number of pages9
JournalACS Infectious Diseases
Volume7
Issue number8
DOIs
StatePublished - Aug 13 2021

Keywords

  • SARS-CoV-2
  • antiviral
  • cytokines
  • ionophore
  • salicylanilides

ASJC Scopus subject areas

  • Infectious Diseases

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