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The recognition of viral nucleic acids by host pattern recognition receptors (PRRs) is critical for initiating innate immune responses against viral infections. These innate immune responses are mediated by the induction of interferons (IFNs), IFN-stimulated genes (ISGs) and pro-inflammatory cytokines. However, regulatory mechanisms are critical to avoid excessive or long-lasting innate immune responses that may cause detrimental hyperinflammation. Here, we identified a novel regulatory function of the ISG, IFN alpha inducible protein 27 (IFI27) in counteracting the innate immune responses triggered by cytoplasmic RNA recognition and binding. Our model systems included three unrelated viral infections caused by Influenza A virus (IAV), Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), and Sendai virus (SeV), and transfection with an analog of double-stranded (ds) RNA. Furthermore, we found that IFI27 has a positive effect on IAV and SARS-CoV-2 replication, most likely due to its ability to counteract host-induced antiviral responses, including in vivo. We also show that IFI27 interacts with nucleic acids and PRR retinoic acid-inducible gene I (RIG-I), being the interaction of IFI27 with RIG-I most likely mediated through RNA binding. Interestingly, our results indicate that interaction of IFI27 with RIG-I impairs RIG-I activation, providing a molecular mechanism for the effect of IFI27 on modulating innate immune responses. Our study identifies a molecular mechanism that may explain the effect of IFI27 in counterbalancing innate immune responses to RNA viral infections and preventing excessive innate immune responses. Therefore, this study will have important implications in drug design to control viral infections and viral-induced pathology.

[EN] Coronaviridae viruses usually cause mild respiratory disease in humans, nevertheless, a new infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally since December 2019, resulting in the ongoing 2019-2021 coronavirus pandemic. The present invention discloses the use of coated iron oxyhydroxide nanoparticles (lOHNPs) for use in the treatment and/or prevention of viral infections caused by Coronaviridae, especially those caused by respiratory syndrome-related coronaviruses such as SARS-CoV and SARS-CoV-2 and MERS-CoV. The iron oxyhydroxide nanoparticles are coated with biocompatible molecules and polymers which bind to the nanoparticle core via oxygen (e.g. sorbitol and sucrose). The lOHNPs were found stable, non-cytotoxic in vitro and can efficiently impair virus replication and transcription. Furthermore, the lOHNPs are suitable for oral, intranasal or parenteral administration in combination with a pharmaceutical carrier., [FR] Les virus Coronaviridae provoquent généralement une maladie respiratoire légère chez l'homme, cependant, une nouvelle maladie infectieuse provoquée par le coronavirus 2 du syndrome respiratoire aigu sévère (SARS-CoV-2) se propage dans le monde depuis décembre 2019, conduisant à la pandémie actuelle de coronavirus de 2019-2021. La présente invention divulgue l'utilisation de nanoparticules d'oxyhydroxyde de fer (lOHNP) enrobées destinées à être utilisées dans le traitement et/ou la prévention d'infections virales provoquées par des Coronaviridae, notamment celles provoquées par des coronavirus associés à des syndromes respiratoires tels que le SARS-CoV, le SARS-CoV-2 et le MERS-CoV. Les nanoparticules d'oxyhydroxyde de fer sont revêtues de molécules et de polymères biocompatibles qui se lient au noyau de nanoparticule via l'oxygène (par exemple, le sorbitol et le saccharose). Les lOHNP se sont révélées stables, non cytotoxiques in vitro et peuvent altérer efficacement la réplication et la transcription du virus. En outre, les lOHNP sont appropriées pour une administration orale, intranasale ou parentérale en combinaison avec un support pharmaceutique.

Coronaviridae viruses usually cause mild respiratory disease in humans, nevertheless a new infectious disease caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally since December 2019, resulting in the ongoing 2019-2021 coronavirus pandemic. The present invention discloses the use of coated iron oxide nanoparticles (IONPs) for use in the treatment and/or prevention of viral infections caused by Coronaviridae, especially those caused by respiratory syndrome-related coronaviruses such as SARS-CoV, SARS-CoV-2 and MERS-CoV. The iron oxide nanoparticles are coated with biocompatible molecules and polymers which bind to the nanoparticle core via oxygen, nitrogen and sulfur donor atoms (e.g. dextran, (3-aminopropyl)triethoxysilane or dimercaptosuccinic acid, respectively). The IONPs were found stable, non-cytotoxic in vitro and can efficiently impair virus replication, transcription and production of infectious virus. Furthermore, the IONPs are suitable for oral, intranasal or parenteral administration in combination with a pharmaceutical carrier.

[EN] Coronaviridae viruses usually cause mild respiratory disease in humans, nevertheless a new infectious disease caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally since December 2019, resulting in the ongoing 2019 2021 coronavirus pandemic. The present invention discloses the use of coated iron oxide nanoparticles (IONPs) for use in the treatment and/or prevention of viral infections caused by Coronaviridae, especially those caused by respiratory syndrome-related coronaviruses such as SARS-CoV, SARS-CoV-2 and MERS-CoV. The iron oxide nanoparticles are coated with biocompatible molecules and polymers which bind to the nanoparticle core via oxygen, nitrogen and sulfur donor atoms (e.g. dextran, (3- aminopropyl)triethoxysilane or dimercaptosuccinic acid, respectively). The IONPs were found stable, non-cytotoxic in vitro and can efficiently impair virus replication, transcription and production of infectious virus. Furthermore, the IONPs are suitable for oral, intranasal or parenteral administration in combination with a pharmaceutical carrier., [FR] Les virus Coronaviridae provoquent généralement une maladie respiratoire légère chez l'être humain, néanmoins une nouvelle maladie infectieuse provoquée par le syndrome respiratoire aigu sévère à coronavirus 2 (SRAS-CoV-2) s'est répandu dans le monde à partir de décembre 2019, conduisant à la pandémie de coronavirus 2019-2021 qui est en cours. La présente invention divulgue l'utilisation de nanoparticules d'oxyde de fer (NPOF) revêtues destinées à être utilisées dans le traitement et/ou la prévention d'infections virales provoquées par des Coronaviridae, notamment celles provoquées par des coronavirus associés au syndrome respiratoire tels que le SRAS-CoV, le SRAS-CoV-2 et le MERS-CoV. Les nanoparticules d'oxyde de fer sont revêtues de molécules biocompatibles et de polymères qui se lient au cœur de la nanoparticule par l'intermédiaire d'atomes donneurs d'oxygène, d'azote et de soufre (par exemple le dextrane, le (3-aminopropyl)triéthoxysilane ou l'acide dimercaptosuccinique, respectivement). Les NPOF se sont révélées stables, non cytotoxiques in vitro,et peuvent altérer efficacement la réplication du virus, la transcription et la production de virus infectieux. En outre, les NPOF sont appropriées pour une administration orale, intranasale ou parentérale en combinaison avec un support pharmaceutique.

Coronaviridae viruses usually cause mild respiratory disease in humans, nevertheless, a new infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally since December 2019, resulting in the ongoing 2019-2021 coronavirus pandemic. The present invention discloses the use of coated iron oxyhydroxide nanoparticles (IOHNPs) for use in the treatment and/or prevention of viral infections caused by Coronaviridae, especially those caused by respiratory syndrome-related coronaviruses such as SARS-CoV and SARS-CoV-2 and MERS-CoV. The iron oxyhydroxide nanoparticles are coated with biocompatible molecules and polymers which bind to the nanoparticle core via oxygen (e.g. sorbitol and sucrose). The IOHNPs were found stable, non-cytotoxic in vitro and can efficiently impair virus replication and transcription. Furthermore, the IOHNPs are suitable for oral, intranasal or parenteral administration in combination with a pharmaceutical carrier.