Evidence map›Paper›PMID 38139188›Full record

ArticleInternational journal of molecular sciences2023

KuINins as a New Class of HIV-1 Inhibitors That Block Post-Integration DNA Repair.

Andrey Anisenko, Simon Galkin, Andrey A Mikhaylov, Maria G Khrenova, Yulia Agapkina, Sergey Korolev, Lidia Garkul, Vasilissa Shirokova, Viktoria A Ikonnikova, Alexander Korlyukov and 3 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.0field-weighted citation impact, top 25% 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

3 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
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

13 authors at 7 institutions in 1 country.

Andrey AnisenkoChemistry Department, Lomonosov Moscow State University, 119992 Moscow, Russia.ORCID 0000-0003-0590-5880
Simon GalkinFaculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119992 Moscow, Russia.ORCID 0000-0003-0479-0591
Andrey A MikhaylovShemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 117997 Moscow, Russia.
Maria G KhrenovaChemistry Department, Lomonosov Moscow State University, 119992 Moscow, Russia.ORCID 0000-0001-7117-3089
Yulia AgapkinaChemistry Department, Lomonosov Moscow State University, 119992 Moscow, Russia.
Sergey KorolevChemistry Department, Lomonosov Moscow State University, 119992 Moscow, Russia.
Lidia GarkulFaculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119992 Moscow, Russia.ORCID 0009-0007-6705-5929
Vasilissa ShirokovaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 117997 Moscow, Russia.
Viktoria A IkonnikovaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 117997 Moscow, Russia.
Alexander KorlyukovNesmeyanov Institute of Organoelement Compounds, 119334 Moscow, Russia.ORCID 0000-0002-5600-9886
Pavel DorovatovskiiNational Research Center "Kurchatov Institute", 123098 Moscow, Russia.
Mikhail BaranovShemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 117997 Moscow, Russia.ORCID 0000-0002-9339-7603
Marina GottikhFaculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119992 Moscow, Russia.
Lomonosov Moscow State University · RUD. Mendeleyev University of Chemical Technology of Russia · RUA. N. Nesmeyanov Institute of Organoelement Compounds · RUInstitute of Bioorganic Chemistry · RUKurchatov Institute · RUPirogov Russian National Research Medical University · RURussian Academy of Sciences · RU

Funding

Russian Science Foundation 19-74-10021Russian Science Foundation 22-14-00073
6 · The paper itself

Abstract

Integration of HIV-1 genomic cDNA results in the formation of single-strand breaks in cellular DNA, which must be repaired for efficient viral replication. Post-integration DNA repair mainly depends on the formation of the HIV-1 integrase complex with the Ku70 protein, which promotes DNA-PK assembly at sites of integration and its activation. Here, we have developed a first-class inhibitor of the integrase-Ku70 complex formation that inhibits HIV-1 replication in cell culture by acting at the stage of post-integration DNA repair. This inhibitor, named s17, does not affect the main cellular function of Ku70, namely its participation in the repair of double-strand DNA breaks through the non-homologous end-joining pathway. Using a molecular dynamics approach, we have constructed a model for the interaction of s17 with Ku70. According to this model, the interaction of two phenyl radicals of s17 with the L76 residue of Ku70 is important for this interaction. The requirement of two phenyl radicals in the structure of s17 for its inhibitory properties was confirmed using a set of s17 derivatives. We propose to stimulate compounds that inhibit post-integration repair by disrupting the integrase binding to Ku70 KuINins.

Indexed as

HIV-1DNADNA-Binding ProteinsDNA End-Joining RepairDNA RepairIntegrasesKu AutoantigenDNADNA-Binding ProteinsIntegrasesKu AutoantigenDNA-PKHIV-1inhibitor of protein–protein interactionintegraseKu70KuINinspost-integration repair

Identifiers

PMID38139188
PMCPMC10744174
OpenAlexW4389553056

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.