In Vitro Antiviral Activity of New Oxazoline Derivatives as Potent Poliovirus Inhibitors

Details

• Alternative Title:
  J Med Chem
• Personal Author:
  Madia, Valentina Noemi ; Messore, Antonella ; Pescatori, Luca ; Saccoliti, Francesco ; Tudino, Valeria ; De Leo, Alessandro ; Scipione, Luigi ; Fiore, Lucia ; Rhoden, Eric ; Manetti, Fabrizio ; Oberste, M. Steven ; Santo, Roberto Di ; Costi, Roberta
• Description:
  The final stages of polio eradication are proving more difficult than the early phases, and the development of effective drugs and treatments is considered a priority; thus, the research is ongoing. A screening of our in-house chemical library against poliovirus Sabin strains led to the identification of compounds 5 and 6 as hits active at submicromolar concentrations. Derivatives of these compounds were synthesized as a preliminary structure-activity-relationship study. Among them, 7 and 11 were highly active against poliovirus Sabin 1-3. Compound 11 was also very potent against a large panel of wild and vaccine-derived polioviruses. Time-of-addition experiments suggest that 5 and 7 could be active at an early stage of viral replication, whereas 11 was active at same concentration at all stages of viral replication. A ligand-based approach was applied to find the common structural features shared by the new compounds and already-known poliovirus inhibitors.
• Subjects:
  Antiviral Agents Article Binding Sites HeLa Cells Humans Molecular Dynamics Simulation Oxazoles Poliovirus Structure-Activity Relationship Virus Replication
• Source:
  J Med Chem. 62(2):798-810
• Pubmed ID:
  30512950
• Pubmed Central ID:
  PMC9169555
• Document Type:
  Journal Article
• Funding:
  CC999999/ImCDC/Intramural CDC HHSUnited States/
• Volume:
  62
• Issue:
  2
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:9fa9ea795dbbc2557ff32017d8bb908a6c1e5eabac3daf99149769bc110626df
• Download URL:
  https://stacks.cdc.gov/view/cdc/119234/cdc_119234_DS1.pdf
• File Type:
  [PDF - 2.37 MB ]