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Viruses . Induction of Innate Immune Response by TLR3 Agonist Protects Mice against SARS-CoV-2 Infection

tetano

Editor, Senior Moderator
Viruses


. 2022 Jan 19;14(2):189.
doi: 10.3390/v14020189.
Induction of Innate Immune Response by TLR3 Agonist Protects Mice against SARS-CoV-2 Infection


Hadas Tamir[SUP] 1 [/SUP], Sharon Melamed[SUP] 1 [/SUP], Noam Erez[SUP] 1 [/SUP], Boaz Politi[SUP] 1 [/SUP], Yfat Yahalom-Ronen[SUP] 1 [/SUP], Hagit Achdout[SUP] 1 [/SUP], Shlomi Lazar[SUP] 2 [/SUP], Hila Gutman[SUP] 2 [/SUP], Roy Avraham[SUP] 1 [/SUP], Shay Weiss[SUP] 1 [/SUP], Nir Paran[SUP] 1 [/SUP], Tomer Israely[SUP] 1 [/SUP]



Affiliations
Free article

Abstract

SARS-CoV-2, a member of the coronavirus family, is the causative agent of the COVID-19 pandemic. Currently, there is still an urgent need in developing an efficient therapeutic intervention. In this study, we aimed at evaluating the therapeutic effect of a single intranasal treatment of the TLR3/MDA5 synthetic agonist Poly(I:C) against a lethal dose of SARS-CoV-2 in K18-hACE2 transgenic mice. We demonstrate here that early Poly(I:C) treatment acts synergistically with SARS-CoV-2 to induce an intense, immediate and transient upregulation of innate immunity-related genes in lungs. This effect is accompanied by viral load reduction, lung and brain cytokine storms prevention and increased levels of macrophages and NK cells, resulting in 83% mice survival, concomitantly with long-term immunization. Thus, priming the lung innate immunity by Poly(I:C) or alike may provide an immediate, efficient and safe protective measure against SARS-CoV-2 infection.

Keywords: COVID-19; Poly(I:C); SARS-CoV-2; TLR3; hACE2-K18 transgenic mice; innate immune response.
 
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