ArticleCellular microbiology2019
Molecular dissection of an inhibitor targeting the HIV integrase dependent preintegration complex nuclear import.
Article in Cellular microbiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- Therapeutic Approaches Interfering with Nuclear Localization Signals: An Emerging Strategy for CNS-Related Diseases.Current neuropharmacology · 2026Review
- GRL-142 binds to and impairs HIV-1 integrase nuclear localization signal and potently suppresses highly INSTI-resistant HIV-1 variants.Science advances · 2023Article
- The Role of Cyclodextrins in COVID-19 Therapy-A Literature Review.International journal of molecular sciences · 2023Review
- Karyopherin-mediated nucleocytoplasmic transport.Nature reviews. Molecular cell biology · 2022Review
- Article
- Role of Transportin-SR2 in HIV-1 Nuclear Import.Viruses · 2021Review
- Antivirals that target the host IMPα/β1-virus interface.Biochemical Society transactions · 2021Review
- The broad spectrum host-directed agent ivermectin as an antiviral for SARS-CoV-2 ?Biochemical and biophysical research communications · 2021Review
- Factors that mold the nuclear landscape of HIV-1 integration.Nucleic acids research · 2021Review
- Therapeutic strategies targeting FOXO transcription factors.Nature reviews. Drug discovery · 2021Review
- Review
- Multifaceted HIV integrase functionalities and therapeutic strategies for their inhibition.The Journal of biological chemistry · 2019Review
- Novel Flavivirus Antiviral That Targets the Host Nuclear Transport Importin α/β1 Heterodimer.Cells · 2019Article
- Novel RU486 (mifepristone) analogues with increased activity against Venezuelan Equine Encephalitis Virus but reduced progesterone receptor antagonistic activity.Scientific reports · 2019Article
- Molecular dissection of an inhibitor targeting the HIV integrase dependent preintegration complex nuclear import.Cellular microbiology · 2019Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human immunodeficiency virus (HIV) continues to be a major contributor to morbidity and mortality worldwide, particularly in developing nations where high cost and logistical issues severely limit the use of current HIV therapeutics. This, combined HIV's high propensity to develop resistance, means that new antiviral agents against novel targets are still urgently required. We previously identified novel anti-HIV agents directed against the nuclear import of the HIV integrase (IN) protein, which plays critical roles in the HIV lifecycle inside the cell nucleus, as well as in transporting the HIV preintegration complex (PIC) into the nucleus. Here we investigate the structure activity relationship of a series of these compounds for the first time, including a newly identified anti-IN compound, budesonide, showing that the extent of binding to the IN core domain correlates directly with the ability of the compound to inhibit IN nuclear transport in a permeabilised cell system. Importantly, compounds that inhibited the nuclear transport of IN were found to significantly decrease HIV viral replication, even in a dividing cell system. Significantly, budesonide or its analogue flunisolide, were able to effect a significant reduction in the presence of specific nuclear forms of the HIV DNA (2-LTR circles), suggesting that the inhibitors work though blocking IN, and potentially PIC, nuclear import. The work presented here represents a platform for further development of these specific inhibitors of HIV replication with therapeutic and prophylactic potential.
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