tetano
Editor, Senior Moderator
Front Immunol
. 2023 Mar 29;14:1166725.
doi: 10.3389/fimmu.2023.1166725. eCollection 2023.
Non-coding RNAs derived from the foot-and-mouth disease virus genome trigger broad antiviral activity against coronaviruses
Miguel Rodríguez-Pulido[SUP] 1 [/SUP], Eva Calvo-Pinilla[SUP] 2 [/SUP], Miryam Polo[SUP] 1 [/SUP], Juan-Carlos Saiz[SUP] 2 [/SUP], Raúl Fernández-González[SUP] 3 [/SUP], Eva Pericuesta[SUP] 3 [/SUP], Alfonso Gutiérrez-Adán[SUP] 3 [/SUP], Francisco Sobrino[SUP] 1 [/SUP], Miguel A Martín-Acebes[SUP] 2 [/SUP], Margarita Sáiz[SUP] 1 [/SUP]
Affiliations
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of a potentially severe respiratory disease, the coronavirus disease 2019 (COVID-19), an ongoing pandemic with limited therapeutic options. Here, we assessed the anti-coronavirus activity of synthetic RNAs mimicking specific domains in the non-coding regions of the foot-and-mouth disease virus (FMDV) genome (ncRNAs). These molecules are known to exert broad-spectrum antiviral activity in cell culture, mice and pigs effectively triggering the host innate immune response. The ncRNAs showed potent antiviral activity against SARS-CoV-2 after transfection in human intestinal Caco-2 and lung epithelium Calu-3 2B4 cells. When the in vivo efficacy of the FMDV ncRNAs was assessed in K18-hACE2 mice, administration of naked ncRNA before intranasal SARS-CoV-2 infection significantly decreased the viral load and the levels of pro-inflammatory cytokines in the lungs compared with untreated infected mice. The ncRNAs were also highly efficacious when assayed against common human HCoV-229E and porcine transmissible gastroenteritis virus (TGEV) in hepatocyte-derived Huh-7 and swine testis ST cells, respectively. These results are a proof of concept of the pan-coronavirus antiviral activity of the FMDV ncRNAs including human and animal divergent coronaviruses and potentially enhance our ability to fight future emerging variants.
Keywords: COVID-19; RNA-based therapy; SARS-CoV-2; antiviral immunity; coronaviruses; foot-and-mouth disease virus (FMDV); non-coding RNA; type-I IFN.
. 2023 Mar 29;14:1166725.
doi: 10.3389/fimmu.2023.1166725. eCollection 2023.
Non-coding RNAs derived from the foot-and-mouth disease virus genome trigger broad antiviral activity against coronaviruses
Miguel Rodríguez-Pulido[SUP] 1 [/SUP], Eva Calvo-Pinilla[SUP] 2 [/SUP], Miryam Polo[SUP] 1 [/SUP], Juan-Carlos Saiz[SUP] 2 [/SUP], Raúl Fernández-González[SUP] 3 [/SUP], Eva Pericuesta[SUP] 3 [/SUP], Alfonso Gutiérrez-Adán[SUP] 3 [/SUP], Francisco Sobrino[SUP] 1 [/SUP], Miguel A Martín-Acebes[SUP] 2 [/SUP], Margarita Sáiz[SUP] 1 [/SUP]
Affiliations
- PMID: 37063925
- PMCID: PMC10090856
- DOI: 10.3389/fimmu.2023.1166725
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of a potentially severe respiratory disease, the coronavirus disease 2019 (COVID-19), an ongoing pandemic with limited therapeutic options. Here, we assessed the anti-coronavirus activity of synthetic RNAs mimicking specific domains in the non-coding regions of the foot-and-mouth disease virus (FMDV) genome (ncRNAs). These molecules are known to exert broad-spectrum antiviral activity in cell culture, mice and pigs effectively triggering the host innate immune response. The ncRNAs showed potent antiviral activity against SARS-CoV-2 after transfection in human intestinal Caco-2 and lung epithelium Calu-3 2B4 cells. When the in vivo efficacy of the FMDV ncRNAs was assessed in K18-hACE2 mice, administration of naked ncRNA before intranasal SARS-CoV-2 infection significantly decreased the viral load and the levels of pro-inflammatory cytokines in the lungs compared with untreated infected mice. The ncRNAs were also highly efficacious when assayed against common human HCoV-229E and porcine transmissible gastroenteritis virus (TGEV) in hepatocyte-derived Huh-7 and swine testis ST cells, respectively. These results are a proof of concept of the pan-coronavirus antiviral activity of the FMDV ncRNAs including human and animal divergent coronaviruses and potentially enhance our ability to fight future emerging variants.
Keywords: COVID-19; RNA-based therapy; SARS-CoV-2; antiviral immunity; coronaviruses; foot-and-mouth disease virus (FMDV); non-coding RNA; type-I IFN.