Non-coding RNAs derived from the foot-and-mouth disease virus genome trigger broad antiviral activity against coronaviruses

Frontiers in Immunology

Immunology

Raúl Fernández-González¹  Eva Pericuesta¹  Alfonso Gutiérrez-Adán¹  Miguel Rodríguez-Pulido²  Francisco Sobrino²  Margarita Sáiz²  Miryam Polo²  Eva Calvo-Pinilla³  Juan-Carlos Saiz³  Miguel A. Martín-Acebes³ 

[1] Animal Reproduction Department, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Consejo Superior de Investigaciones Científicas (INIA-CSIC), Madrid, Spain;Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid (UAM), Madrid, Spain;Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Consejo Superior de Investigaciones Científicas (INIA-CSIC), Madrid, Spain;

关键词: non-coding RNA;    foot-and-mouth disease virus (FMDV);    SARS-CoV-2;    COVID-19;    type-I IFN;    antiviral immunity;    RNA-based therapy;    coronaviruses;   

DOI  :  10.3389/fimmu.2023.1166725

 received in 2023-02-15, accepted in 2023-03-20,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2023 Rodríguez-Pulido, Calvo-Pinilla, Polo, Saiz, Fernández-González, Pericuesta, Gutiérrez-Adán, Sobrino, Martín-Acebes and Sáiz