The next ten stories on antiviral drug discovery (part E): advents, advances, and adventures

Clercq, Erik De

doi:10.1002/med.20179

Cited by 47 publications

(39 citation statements)

References 254 publications

(231 reference statements)

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“…Peramivir was briefly licensed for emergency use during the swine-origin H1N1 epidemic in an injectable formulation for patients on ventilators and is currently completing clinical trials, and several other backbones are being tested as well as further derivatives of zanamivir. Several recent reviews describe these new developments 3,5,6,66–69 .…”

Section: Na Inhibitors and Resistance Mutationsmentioning

confidence: 99%

Influenza neuraminidase

Air

2011

Influenza Resp Viruses

208

216

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Influenza neuraminidase is the target of two licensed antivirals that have been very successful, with several more in development. However, neuraminidase has been largely ignored as a vaccine target despite evidence that inclusion of neuraminidase in the subunit vaccine gives increased protection. This article describes current knowledge on the structure, enzyme activity and antigenic significance of neuraminidase.

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Section: Na Inhibitors and Resistance Mutationsmentioning

confidence: 99%

Influenza neuraminidase

Air

2011

Influenza Resp Viruses

208

216

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“…The incidence of CMV infections such as retinitis has recently dropped drastically thanks to the successful treatment of AIDS with the current anti-HIV drugs. Yet the broad anti-DNA virus activity of (S)-HPMPC, similar to that of (S)-HPMPA (71), makes the compound potentially useful for the treatment of various DNA virus infections, poxvirus infections (74), and papilloma and polyoma virus infections (75,76). (S)-HPMPC would be more effective than smallpox vaccination against a lethal monkeypox virus infection (77).…”

Section: The Acyclic Nucleoside Phosphonatesmentioning

confidence: 99%

A 40-Year Journey in Search of Selective Antiviral Chemotherapy*

Clercq

2011

Annu. Rev. Pharmacol. Toxicol.

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147

144

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My search for a selective antiviral chemotherapy started more than 40 years ago with interferon inducers, then shifted to nucleoside analogs with the discovery of BVDU (brivudin), a highly selective anti-HSV-1 and anti-VZV agent, and to dideoxynucleoside analogs such as d4T (stavudine), anti-HIV agents. The search culminated in the discovery of acyclic nucleoside phosphonates (ANPs) (in collaboration with Antonin Holý), a key class of compounds active against HIV, hepatitis B virus, and DNA viruses at large; the best known of these compounds is tenofovir. Along the way, the principle of the non-nucleoside reverse transcriptase inhibitors (NNRTIs) was established. This work, initiated in collaboration with the late Paul A.J. Janssen, eventually led to the identification of rilpivirine as perhaps an "ideal" NNRTI.1

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“…They belong to different categories: reverse transcriptase inhibitors (RTIs), protease inhibitors (PIs); fusion inhibitors (FIs), coreceptor inhibitors (CRIs), and integrase inhibitors (INIs). 2 However, even the combination of these drugs is not sufficient enough to stop the progression of AIDS partly due to the emergence of drug-resistant HIV-1 mutants as well as the severe side effects. [3][4][5] Therefore, alternative strategies need to be considered and new targets need to be identified to combat the growing AIDS pandemic.…”

Section: Introductionmentioning

confidence: 99%

Small molecules targeting the interaction between HIV-1 integrase and LEDGF/p75 cofactor

Luca

Ferro

Gitto

et al. 2010

Bioorganic & Medicinal Chemistry

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Keywords:HIV-1 integrase LEDGF/p75 Protein-protein interactions Molecular docking GRID a b s t r a c tThe search of small molecules as protein-protein interaction inhibitors represents a new attractive strategy to develop anti-HIV-1 agents. We previously reported a computational study that led to the discovery of new inhibitors of the interaction between enzyme HIV-1 integrase (IN) and the nuclear protein lens epithelium growth factor LEDGF/p75. 1 Herein, we describe new findings about the binding site of LEDGF/p75 on IN employing a different computational approach. In this way further structural requirements, helpful to disrupt LEDGF/p75-IN binding, have been identified. The main result of this work was the exploration of a relevant hydrophobic region. So we planned the introduction of suitable and simple chemical modifications on our previously reported 'hit' and the new synthesized compounds were subjected to biological tests.The results obtained demonstrate that the hydrophobic pocket could play a key role in improving inhibitory efficacy thus opening new suggestions to design active ligands.

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The next ten stories on antiviral drug discovery (part E): advents, advances, and adventures

Cited by 47 publications

References 254 publications

Influenza neuraminidase

Influenza neuraminidase

A 40-Year Journey in Search of Selective Antiviral Chemotherapy*

Small molecules targeting the interaction between HIV-1 integrase and LEDGF/p75 cofactor

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