Knockdown of different influenza A virus subtypes in cell culture by a single antisense oligodeoxyribonucleotide

Левина, А. С.; Репкова, М. Н.; Мазуркова, Н. А.; Макаревич, Е. В.; Ismagilov, Z. R.; Зарытова, В. Ф.

doi:10.1016/j.ijantimicag.2015.03.004

Cited by 32 publications

(16 citation statements)

References 13 publications

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“…The inactivating rate on H9N2 viruses was shown to reach up to 100%, when the UV intensity is 0.5 mW/cm 2 , the quantity of H9N2 is 0.1 ml, and the UV illumination time is 2.5 h. In another study [101], titanium dioxide nanoparticles electrostatically bound to DNA (v3’) targeted to the 3’ end of the non-encoding region of the viral (H3N2) DNA was able to efficiently inhibit virus reproduction. Further follow up studies showed a similar activity of the DNA tagged titanium dioxide nanoparticles against H5N1 and H1N1 viruses [102]. …”

Section: 3 Studies On Influenza Virusmentioning

confidence: 99%

Role of metal and metal oxide nanoparticles as diagnostic and therapeutic tools for highly prevalent viral infections

Yadavalli

Shukla

2017

Nanomedicine: Nanotechnology, Biology and Medicine

144

111

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Nanotechnology is increasingly playing important roles in various fields including virology. The emerging use of metal or metal oxide nanoparticles in virus targeting formulations shows the promise of improved diagnostic or therapeutic ability of the agents while uniquely enhancing the prospects of targeted drug delivery. Although a number of nanoparticles varying in composition, size, shape, and surface properties have been approved for human use, the candidates being tested or approved for clinical diagnosis and treatment of viral infections are relatively less in number. Challenges remain in this domain due to a lack of essential knowledge regarding the in vivo comportment of nanoparticles during viral infections. This review provides a broad overview of recent advances in diagnostic, prophylactic and therapeutic applications of metal and metal oxide nanoparticles in Human Immunodeficiency Virus, Hepatitis virus, influenza virus and Herpes virus infections. Types of nanoparticles commonly used and their broad applications have been explained in this review.

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Section: 3 Studies On Influenza Virusmentioning

confidence: 99%

Role of metal and metal oxide nanoparticles as diagnostic and therapeutic tools for highly prevalent viral infections

Yadavalli

Shukla

2017

Nanomedicine: Nanotechnology, Biology and Medicine

144

111

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“…It was shown in our recent paper [15] that the TiO 2 •PL-DNA 1 nanocomposite efficiently inhibit the reproduction of not only H3N2 subtype of IAV but also the H1N1 and highly pathogenic avian H5N1 subtypes (inhibition by factors of ca. 9000, 5000, and 1000, respectively) (Fig.…”

Section: Resultsmentioning

confidence: 92%

TiO2∼DNA nanocomposites as efficient site-specific antiviral agents against influenza A virus in cell culture

Левина

Репкова

Зарытова

et al. 2015

2015 IEEE 15th International Conference on Nanotechnology (IEEE-NANO)

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The development of new antiviral nucleic acidbased drugs and the search for their efficient delivery into cells are an urgent task. We developed methods of immobilizing DNA fragments to titanium dioxide nanoparticles with the formation of TiO 2~D NA nanocomposites. It is shown that DNA fragments in nanocomposites retain their ability to form complementary complexes and can be delivered into cells without transfection agents and other methods of exposure. The proposed nanocomposites were shown to be efficient agents to affect target nucleic acids inside cells with an example of inhibition of influenza A virus (IAV) reproduction. The nanocomposites bearing the DNA 1 fragment targeted to the 3'-noncoding region of segment 5 (-)vRNA showed a low toxicity (TC 50 1500 g/ml) and a high antiviral activity against different IAV subtypes (H1N1, H5N1, and H3N2) in infected MDCK cells (the virus replication was inhibited by up to four orders of magnitude). The IC 50 value for nanocomposites was estimated to be 1.5 g/ml (30 nM for DNA), so its selectivity index was calculated as ~1000. Control samples, i.e., nanoparticles without DNA fragments and vise versa as well as unbound DNA fragments in the presence of nanoparticles were much less active, if at all. A high sitespecificity of the action of designed nanocomposites (~3000-fold difference between the effect of the nanocomposites containing target-directed DNA and DNA with a random sequence) indicates a pronounced antisense effect. The presented types of nanocomposites can be applied in the thriving technology of drug delivery to achieve high therapeutic and biological efficacy.

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“… a Numbering of nucleotides are given for (+)RNA; b Nanocomposite TiO 2 ·PL–DNA containing this DNA fragment was used in previous works [18–19]. …”

Section: Resultsmentioning

confidence: 99%

“…It was shown that TiO 2 ·PL–DNA nanocomposites can penetrate into cells without any additional treatment (i.e., transfection agents or physical impact). It was demonstrated that these nanocomposites exhibited a low toxicity and very high activity against IAV in the cell culture [18–19]. Only one site in the IAV 5 segment was used in our previous works.…”

Section: Introductionmentioning

confidence: 99%

High antiviral effect of TiO₂·PL–DNA nanocomposites targeted to conservative regions of (−)RNA and (+)RNA of influenza A virus in cell culture

Левина¹,

Репкова²,

Bessudnova³

et al. 2016

Beilstein J. Nanotechnol.

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Summary Background: The development of new antiviral drugs based on nucleic acids is under scrutiny. An important problem in this aspect is to find the most vulnerable conservative regions in the viral genome as targets for the action of these agents. Another challenge is the development of an efficient system for their delivery into cells. To solve this problem, we proposed a TiO2·PL–DNA nanocomposite consisting of titanium dioxide nanoparticles and polylysine (PL)-containing oligonucleotides. Results: The TiO2·PL–DNA nanocomposites bearing the DNA fragments targeted to different conservative regions of (−)RNA and (+)RNA of segment 5 of influenza A virus (IAV) were studied for their antiviral activity in MDCK cells infected with the H1N1, H5N1, and H3N2 virus subtypes. Within the negative strand of each of the studied strains, the efficiency of DNA fragments increased in the direction of its 3’-end. Thus, the DNA fragment aimed at the 3’-noncoding region of (−)RNA was the most efficient and inhibited the reproduction of different IAV subtypes by 3–4 orders of magnitude. Although to a lesser extent, the DNA fragments targeted at the AUG region of (+)RNA and the corresponding region of (−)RNA were also active. For all studied viral subtypes, the nanocomposites bearing the DNA fragments targeted to (−)RNA appeared to be more efficient than those containing fragments aimed at the corresponding (+)RNA regions. Conclusion: The proposed TiO2·PL–DNA nanocomposites can be successfully used for highly efficient and site-specific inhibition of influenza A virus of different subtypes. Some patterns of localization of the most vulnerable regions in IAV segment 5 for the action of DNA-based drugs were found. The (−)RNA strand of IAV segment 5 appeared to be more sensitive as compared to (+)RNA.

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Knockdown of different influenza A virus subtypes in cell culture by a single antisense oligodeoxyribonucleotide

Cited by 32 publications

References 13 publications

Role of metal and metal oxide nanoparticles as diagnostic and therapeutic tools for highly prevalent viral infections

Role of metal and metal oxide nanoparticles as diagnostic and therapeutic tools for highly prevalent viral infections

TiO2∼DNA nanocomposites as efficient site-specific antiviral agents against influenza A virus in cell culture

High antiviral effect of TiO₂·PL–DNA nanocomposites targeted to conservative regions of (−)RNA and (+)RNA of influenza A virus in cell culture

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Knockdown of different influenza A virus subtypes in cell culture by a single antisense oligodeoxyribonucleotide

Cited by 32 publications

References 13 publications

Role of metal and metal oxide nanoparticles as diagnostic and therapeutic tools for highly prevalent viral infections

Role of metal and metal oxide nanoparticles as diagnostic and therapeutic tools for highly prevalent viral infections

TiO2∼DNA nanocomposites as efficient site-specific antiviral agents against influenza A virus in cell culture

High antiviral effect of TiO2·PL–DNA nanocomposites targeted to conservative regions of (−)RNA and (+)RNA of influenza A virus in cell culture

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High antiviral effect of TiO₂·PL–DNA nanocomposites targeted to conservative regions of (−)RNA and (+)RNA of influenza A virus in cell culture