posted on 2021-08-02, 19:03authored bySteven Blake, Namir Shaabani, Lisa M. Eubanks, Junki Maruyama, John T. Manning, Nathan Beutler, Slobodan Paessler, Henry Ji, John R. Teijaro, Kim D. Janda
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.