Evidence map›Paper›PMID 33837568›Full record

ArticleAllergy2021

Silencing of SARS-CoV-2 with modified siRNA-peptide dendrimer formulation.

Musa Khaitov, Alexandra Nikonova, Igor Shilovskiy, Ksenia Kozhikhova, Ilya Kofiadi, Lyudmila Vishnyakova, Alexander Nikolskii, Pia Gattinger, Valeria Kovchina, Ekaterina Barvinskaia and 22 more

Open access · bronzeAbstract read
In one paragraph

Article in Allergy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
7.7field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

55 citing papers in PubMed, 114 citations in OpenAlex.

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  18. Prophylactic intranasal administration of lipid nanoparticle formulated siRNAs reduce SARS-CoV-2 and RSV lung infection.Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi · 2023
    Article
  19. Antiviral Therapy of COVID-19.International journal of molecular sciences · 2023
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

32 authors at 5 institutions in 2 countries.

Musa KhaitovNRC Institute of Immunology FMBA, Moscow, Russia.ORCID 0000-0003-4961-9640
Alexandra NikonovaNRC Institute of Immunology FMBA, Moscow, Russia.ORCID 0000-0001-9610-0935
Igor ShilovskiyNRC Institute of Immunology FMBA, Moscow, Russia.ORCID 0000-0001-5343-4230
Ksenia KozhikhovaNRC Institute of Immunology FMBA, Moscow, Russia.ORCID 0000-0001-5124-6826
Ilya KofiadiNRC Institute of Immunology FMBA, Moscow, Russia.ORCID 0000-0001-9280-8282
Lyudmila VishnyakovaNRC Institute of Immunology FMBA, Moscow, Russia.
Alexander NikolskiiNRC Institute of Immunology FMBA, Moscow, Russia.ORCID 0000-0002-4169-0760
Pia GattingerMedical University of Vienna, Vienna, Austria.ORCID 0000-0001-6724-8543
Valeria KovchinaNRC Institute of Immunology FMBA, Moscow, Russia.ORCID 0000-0003-3134-5776
Ekaterina BarvinskaiaNRC Institute of Immunology FMBA, Moscow, Russia.
Kirill YumashevNRC Institute of Immunology FMBA, Moscow, Russia.
Valeriy SmirnovNRC Institute of Immunology FMBA, Moscow, Russia.
Artem MaerleNRC Institute of Immunology FMBA, Moscow, Russia.ORCID 0000-0003-1184-4965
Ivan KozlovNRC Institute of Immunology FMBA, Moscow, Russia.
Artem ShatilovNRC Institute of Immunology FMBA, Moscow, Russia.
Anastasiia TimofeevaNRC Institute of Immunology FMBA, Moscow, Russia.
Sergey AndreevNRC Institute of Immunology FMBA, Moscow, Russia.
Olesya KoloskovaNRC Institute of Immunology FMBA, Moscow, Russia.ORCID 0000-0003-3949-8582
Nadezhda KuznetsovaFederal State Budget Institution "National Research Centre for Epidemiology and Microbiology named after Honorary Academician N. F.Gamaleya" of the Ministry of Health of the Russian Federation, Moscow, Russia.
Daria VasinaFederal State Budget Institution "National Research Centre for Epidemiology and Microbiology named after Honorary Academician N. F.Gamaleya" of the Ministry of Health of the Russian Federation, Moscow, Russia.ORCID 0000-0003-1965-0700
Maria NikiforovaFederal State Budget Institution "National Research Centre for Epidemiology and Microbiology named after Honorary Academician N. F.Gamaleya" of the Ministry of Health of the Russian Federation, Moscow, Russia.ORCID 0000-0001-5823-6508
Sergei RybalkinNRC Institute of Immunology FMBA, Moscow, Russia.
Ilya SergeevNRC Institute of Immunology FMBA, Moscow, Russia.
Dmitriy TrofimovNRC Institute of Immunology FMBA, Moscow, Russia.
Alexander MartynovNRC Institute of Immunology FMBA, Moscow, Russia.
Igor BerzinFederal Medico-biological Agency of Russia (FMBA Russia), Moscow, Russia.
Vladimir GushchinFederal State Budget Institution "National Research Centre for Epidemiology and Microbiology named after Honorary Academician N. F.Gamaleya" of the Ministry of Health of the Russian Federation, Moscow, Russia.ORCID 0000-0002-9397-3762
Aleksey Kovalchuk48 Central Research Institute of the Ministry of Defense of the Russian Federation, Moscow, Russia.
Sergei Borisevich48 Central Research Institute of the Ministry of Defense of the Russian Federation, Moscow, Russia.ORCID 0000-0002-6742-3919
Rudolf ValentaNRC Institute of Immunology FMBA, Moscow, Russia.ORCID 0000-0001-5944-3365
Rakhim KhaitovNRC Institute of Immunology FMBA, Moscow, Russia.ORCID 0000-0003-3064-8871
Veronica SkvortsovaFederal Medico-biological Agency of Russia (FMBA Russia), Moscow, Russia.
Institute of Immunology and Physiology · RUMinistry of Health of the Russian Federation · RU46th Central Research Institute of the Ministry of Defense of the Russian FederationFederal Medical-Biological Agency · RUMedical University of Vienna · AT

Funding

Federal Medico-biological Agency of Russia
6 · The paper itself

Abstract

backgroundFirst vaccines for prevention of Coronavirus disease 2019 (COVID-19) are becoming available but there is a huge and unmet need for specific forms of treatment. In this study we aimed to evaluate the anti-SARS-CoV-2 effect of siRNA both in vitro and in vivo.

methodsTo identify the most effective molecule out of a panel of 15 in silico designed siRNAs, an in vitro screening system based on vectors expressing SARS-CoV-2 genes fused with the firefly luciferase reporter gene and SARS-CoV-2-infected cells was used. The most potent siRNA, siR-7, was modified by Locked nucleic acids (LNAs) to obtain siR-7-EM with increased stability and was formulated with the peptide dendrimer KK-46 for enhancing cellular uptake to allow topical application by inhalation of the final formulation - siR-7-EM/KK-46. Using the Syrian Hamster model for SARS-CoV-2 infection the antiviral capacity of siR-7-EM/KK-46 complex was evaluated.

resultsWe identified the siRNA, siR-7, targeting SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) as the most efficient siRNA inhibiting viral replication in vitro. Moreover, we showed that LNA-modification and complexation with the designed peptide dendrimer enhanced the antiviral capacity of siR-7 in vitro. We demonstrated significant reduction of virus titer and lung inflammation in animals exposed to inhalation of siR-7-EM/KK-46 in vivo.

conclusionsThus, we developed a therapeutic strategy for COVID-19 based on inhalation of a modified siRNA-peptide dendrimer formulation. The developed medication is intended for inhalation treatment of COVID-19 patients.

Indexed as

COVID-19DendrimersAnimalsAntiviral AgentsHumansPeptidesRNA, Small InterferingRNA, ViralSARS-CoV-2Antiviral AgentsDendrimersPeptidesRNA, Small InterferingRNA, ViralCOVID-19LNApeptide dendrimersSARS-CoV-2siRNA

Identifiers

PMID33837568
PMCPMC8251148
OpenAlexW3130817332

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.