Virtual Screening and Biological Validation of Novel Influenza Virus PA Endonuclease Inhibitors
نویسندگان
چکیده
منابع مشابه
Structural and Biochemical Basis for Development of Influenza Virus Inhibitors Targeting the PA Endonuclease
Emerging influenza viruses are a serious threat to human health because of their pandemic potential. A promising target for the development of novel anti-influenza therapeutics is the PA protein, whose endonuclease activity is essential for viral replication. Translation of viral mRNAs by the host ribosome requires mRNA capping for recognition and binding, and the necessary mRNA caps are cleave...
متن کاملAn Integrated Biological Approach to Guide the Development of Metal-Chelating Inhibitors of Influenza Virus PA Endonuclease s
The influenza virus PA endonuclease, which cleaves capped cellular pre-mRNAs to prime viral mRNA synthesis, is a promising target for novel anti–influenza virus therapeutics. The catalytic center of this enzyme resides in the N-terminal part of PA (PA-Nter) and contains two (or possibly one or three) Mg or Mn ions, which are critical for its catalytic function. There is great interest in PA inh...
متن کاملAn integrated biological approach to guide the development of metal-chelating inhibitors of influenza virus PA endonuclease.
The influenza virus PA endonuclease, which cleaves capped cellular pre-mRNAs to prime viral mRNA synthesis, is a promising target for novel anti-influenza virus therapeutics. The catalytic center of this enzyme resides in the N-terminal part of PA (PA-Nter) and contains two (or possibly one or three) Mg(2+) or Mn(2+) ions, which are critical for its catalytic function. There is great interest i...
متن کاملN-acylhydrazone inhibitors of influenza virus PA endonuclease with versatile metal binding modes
Influenza virus PA endonuclease has recently emerged as an attractive target for the development of novel antiviral therapeutics. This is an enzyme with divalent metal ion(s) (Mg(2+) or Mn(2+)) in its catalytic site: chelation of these metal cofactors is an attractive strategy to inhibit enzymatic activity. Here we report the activity of a series of N-acylhydrazones in an enzymatic assay with P...
متن کاملFunctional properties of the novel PA-X endonuclease of human influenza virus
The PA subunit of the RNA dependent RNA polymerase of influenza virus is an endonuclease required for the cap-snatching mechanism leading to the synthesis of viral mRNA. Recently, the PA-X protein has been discovered in human influenza, which is translated from an alternative open reading frame within the PA gene coding sequence, resulting from a ribosomal frameshifting. The PA-X retains the N-...
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ژورنال
عنوان ژورنال: ACS Medicinal Chemistry Letters
سال: 2015
ISSN: 1948-5875,1948-5875
DOI: 10.1021/acsmedchemlett.5b00109