Small RNAs targeting the 5′ end of the viral polymerase gene segments specifically interfere with influenza type A virus replication

Martelli, Francesco; Salata, Cristiano; Calistri, Arianna; Parolin, Cristina; Azzi, Alberta; Palù, Giorgio; Giannecchini, Simone

doi:10.1016/j.jbiotec.2015.06.391

Cited by 5 publications

(3 citation statements)

References 17 publications

(25 reference statements)

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“…44 We used hNECs cultured in ALI, which form a pseudostratified epithelium, vastly distinct from commercially available immortalized respiratory monolayer cell cultures, which may not represent the authentic biological features of the nasal epithelium. [45][46][47] Building on our in vivo model that provided evidence that the CD151 knockout phenotype can protect the murine respiratory tract from IAV infection, the in vitro model further confirmed the mechanism of CD151 in the nuclear export of vRNP. This model also revealed that CD151 interacts with NP among hNEC samples derived from different individuals.…”

Section: Discussionmentioning

confidence: 65%

CD151, a novel host factor of nuclear export signaling in influenza virus infection

Qiao

Yan

Tan

et al. 2018

Journal of Allergy and Clinical Immunology

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Our results provide new mechanistic insights into our understanding of IAV infection. We show that CD151 is a critical novel host factor of nuclear export signaling whereby the IAV nuclear export uses it to complement its own nuclear export proteins (a site not targeted by current therapy), making this regulation unique, and holds promise for the development of novel alternative/complementary strategies to reduce IAV severity.

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Section: Discussionmentioning

confidence: 65%

CD151, a novel host factor of nuclear export signaling in influenza virus infection

Qiao

Yan

Tan

et al. 2018

Journal of Allergy and Clinical Immunology

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“…In this context, for influenza virus studies a powerful S-ON antiviral activity has been proved [17][18][19]. Additionally, a small interfering RNA (siRNA) was developed for treating influenza virus infections in vivo and in vitro [20,39]. It is of note that experimental evidence reported that targeting packaging signals with nucleic acid-based antivirals may be difficult for the virus to evade through resistance mutations [20].…”

Section: Discussionmentioning

confidence: 99%

“…Some evidence has shown that the genomes of RNA viruses contain cis-acting RNA elements located at the 5 and 3 untranslated regions and in the coding region, forming stem-loop structures implicated in the RNA and viral or host proteins RNA-RNA or RNA-protein interactions to fulfil viral genome replication, translation, and assembly [11]. The genomic packaging sequences of the influenza virus, extensively characterized for their implications for viral assembly and propagation [12][13][14][15], have been used to develop new nucleic-acid-based antiviral strategies [16][17][18][19][20]. Although not as well studied as influenza virus, the SARS-CoV-2 RNA genomes possess similar features that mediate viral assembly and that are potentially targetable by nucleic-acid molecules [10,[21][22][23][24][25][26].…”

Section: Introductionmentioning

confidence: 99%

Antiviral Activity of Oligonucleotides Targeting the SARS-CoV-2 Genomic RNA Stem-Loop Sequences within the 3′-End of the ORF1b

et al. 2022

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Increased evidence shows vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibited no long-term efficacy and limited worldwide availability, while existing antivirals and treatment options have only limited efficacy. In this study, the main objective was the development of antiviral strategies using nucleic acid-based molecules. To this purpose, partially overlapped 6-19-mer phosphorothioate deoxyoligonucleotides (S-ONs) designed on the SARS-CoV-2 genomic RNA stem-loop packaging sequences within the 3′ end of the ORF1b were synthetized using the direct and complementary sequence. Among the S-ONs tested, several oligonucleotides exhibited a fifty percent inhibitory concentration antiviral activity ranging from 0.27 to 34 μM, in the absence of cytotoxicity. The S-ON with a scrambled sequence used in the same conditions was not active. Moreover, selected 10-mer S-ONs were tested using different infectious doses and against different SARS-CoV-2 variants, showing comparable antiviral activity that was abrogated when the central sequence was mutated. Experiments to evaluate the intracellular functional target localization of the S-ON inhibitory activity were also performed. Collectively the data indicate that the SARS-CoV-2 packaging region in the 3′ end of the ORF1b may be a promising target candidate for further investigation to develop innovative nucleic-acid-based antiviral therapy.

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Cleavage of influenza RNA by using a human PUF-based artificial RNA-binding protein–staphylococcal nuclease hybrid

Mori

Nakamura

Masaoka

et al. 2016

Biochemical and Biophysical Research Communications

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Small RNAs targeting the 5′ end of the viral polymerase gene segments specifically interfere with influenza type A virus replication

Cited by 5 publications

References 17 publications

CD151, a novel host factor of nuclear export signaling in influenza virus infection

CD151, a novel host factor of nuclear export signaling in influenza virus infection

Antiviral Activity of Oligonucleotides Targeting the SARS-CoV-2 Genomic RNA Stem-Loop Sequences within the 3′-End of the ORF1b

Cleavage of influenza RNA by using a human PUF-based artificial RNA-binding protein–staphylococcal nuclease hybrid

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