1. Non-coding RNAs derived from the foot-and-mouth disease virus genome trigger broad antiviral activity against coronaviruses
- Author
-
Rodríguez-Pulido, M., Calvo Pinilla, Eva María, Polo, Miryam, Saiz Calahorra, Juan Carlos, Fernández-González, Raúl, Pericuesta Camacho, Eva, Gutiérrez-Adán, Alfonso, Sobrino, F., Martín-Acebes, M. A., Sáiz, Margarita, European Commission, CSIC - Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Ministerio de Ciencia e Innovación (España), Rodríguez-Pulido, M., Calvo Pinilla, Eva María, Polo, Miryam, Saiz Calahorra, Juan Carlos, Fernández-González, Raúl, Pericuesta Camacho, Eva, Gutiérrez-Adán, Alfonso, Sobrino, F., Martín-Acebes, M. A., and Sáiz, Margarita
- Subjects
RNA-based therapy ,SARS-CoV-2 ,Coronaviruses ,Foot-and-mouth disease virus (FMDV) ,Type-I IFN ,Immunology ,COVID-19 ,Immunology and Allergy ,Antiviral immunity ,Non-coding RNA - Abstract
12 Pág., 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., This research work was funded by the European Commission – NextGenerationEU (Regulation EU 2020/2094), through CSIC´s Global Health Platform (PTI Salud Global), grants SGL 2103051 (to MS and FS) and SGL2103053 (to MM-A). It was further supported by the Spanish Ministry of Science and Innovation, grant PID2020-113184RB-C21 (to FS and MS) and by grant S018/BAA-4370 (co-financed by the Autonomous Community of Madrid and EC FEDER funds, to FS). MP was the recipient of a scholarship from the CSIC´s JAE Intro program.
- Published
- 2023