Learning from structure-based drug design and new antivirals targeting the ribonucleoprotein complex for the treatment of influenza
| Autor: | Rob W. H. Ruigrok, Alexandre Monod, Bogdan Tarus, Thibaut Crépin, Christopher Swale, Alice Tissot, Anny Slama-Schwok, Bernard Delmas |
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| Přispěvatelé: | Centre National de la Recherche Scientifique (CNRS), Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut National de la Recherche Agronomique (INRA), Agence Nationale de la Recherche Blan-130701 Blanc -14-CE09-0017, HPC resources of IDRIS 2012-076378, French Infrastructure for Integrated Structural Biology ANR-10-INSB-05-02, Alliance Grenobloise pour la Biologie Structurale et Cellulaire Integrees within the Grenoble Partnership for Structural Biology ANR-10-LABX-49-01, Unit of Virus Host Cell Interactions (UVHCI), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Drug
nucleoprotein inhibitors replication and transcription Rimantadine Viral protein media_common.quotation_subject Biology MEMBRANE-FUSION medicine.disease_cause Virus Replication Antiviral Agents M2 PROTON CHANNEL neuraminidase and matrix 2 inhibitors Structure-Activity Relationship antivirals [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication Drug Discovery Drug Resistance Viral Influenza Human B VIRUSES medicine Animals Humans CRYSTAL-STRUCTURE BIOLOGICAL EVALUATION Polymerase media_common A VIRUS NUCLEOPROTEIN Amantadine endonuclease domain VIRAL-RNA PROMOTER resistance ribonucleoprotein complex Virology POLYMERASE INHIBITORS 3. Good health Nucleoprotein BINDING-SITE [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biomolecules [q-bio.BM] Viral replication Ribonucleoproteins cap-binding domain Drug Design NEURAMINIDASE INHIBITORS biology.protein [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology Neuraminidase medicine.drug |
| Zdroj: | Expert Opinion on Drug Discovery Expert Opinion on Drug Discovery, Informa Healthcare, 2015, 10 (4), pp.345-371. ⟨10.1517/17460441.2015.1019859⟩ Expert Opinion on Drug Discovery, Informa Healthcare, 2015, 10 (4), pp.345-71 |
| ISSN: | 1746-0441 1746-045X |
| DOI: | 10.1517/17460441.2015.1019859⟩ |
| Popis: | International audience; Introduction: Influenza viruses are a threat to human health. There are presently only two methods for treating influenza: vaccines, which require yearly updates, and two classes of antivirals that suffer with the problem of resistance by current human influenza viruses; this is especially the case with amantadine and rimantadine. Consequently, there is an urgent need for the development of new antivirals with new mechanisms of action. Areas covered: In this review, the authors focus on viral protein domains, their associated activity and their inhibition by small molecules defined by a structure-based design with a special emphasis on the ribonucleoprotein complex and its inhibitors. Several new classes of antiviral candidates targeting viral replication through individual domains of the polymerase and the nucleoprotein (NP) have been developed through structure-based design. Expert opinion: To date, the antivirals targeting neuraminidase are by far the most developed and potent. Antiviral candidates targeting the NP and polymerase domains are in the pipeline but their pharmacokinetics needs further studies. The recently published structures of the polymerase expand the possibilities for development of new antivirals. Combination therapies targeting conserved viral targets and new cellular proteins or exploiting drug promiscuity hold promises to fight against the emergence of resistance. |
| Databáze: | OpenAIRE |
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