title: Therapeutic Potential of Spirooxindoles as Antiviral Agents.
abstract: Antiviral therapeutics with profiles of high potency, low resistance, panserotype, and low toxicity remain challenging, and obtaining such agents continues to be an active area of therapeutic development. Due to their unique three-dimensional structural features, spirooxindoles have been identified as privileged chemotypes for antiviral drug development. Among them, spiro-pyrazolopyridone oxindoles have been recently reported as potent inhibitors of dengue virus NS4B, leading to the discovery of an orally bioavailable preclinical candidate (R)-44 with excellent in vivo efficacy in a dengue viremia mouse model. This review highlights recent advances in the development of biologically active spirooxindoles for their antiviral potential, primarily focusing on the structure-activity relationships (SARs) and modes of action, as well as future directions to achieve more potent analogues toward a viable antiviral therapy.
authors.affiliation: Chemical Biology Program, Department of Pharmacology and Toxicology, ‡Department of Biochemistry & Molecular Biology, #Sealy Center for Structural Biology & Molecular Biophysics, and ⊥Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch , 301 University Boulevard, Galveston, Texas 77555, United States.
authors.forename: Na
authors.initials: N
authors.lastname: Ye
authors.affiliation: Chemical Biology Program, Department of Pharmacology and Toxicology, ‡Department of Biochemistry & Molecular Biology, #Sealy Center for Structural Biology & Molecular Biophysics, and ⊥Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch , 301 University Boulevard, Galveston, Texas 77555, United States.
authors.forename: Haiying
authors.initials: H
authors.lastname: Chen
authors.affiliation: Chemical Biology Program, Department of Pharmacology and Toxicology, ‡Department of Biochemistry & Molecular Biology, #Sealy Center for Structural Biology & Molecular Biophysics, and ⊥Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch , 301 University Boulevard, Galveston, Texas 77555, United States.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Wold
authors.affiliation: Chemical Biology Program, Department of Pharmacology and Toxicology, ‡Department of Biochemistry & Molecular Biology, #Sealy Center for Structural Biology & Molecular Biophysics, and ⊥Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch , 301 University Boulevard, Galveston, Texas 77555, United States.
authors.forename: Pei-Yong
authors.initials: PY
authors.lastname: Shi
authors.affiliation: Chemical Biology Program, Department of Pharmacology and Toxicology, ‡Department of Biochemistry & Molecular Biology, #Sealy Center for Structural Biology & Molecular Biophysics, and ⊥Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch , 301 University Boulevard, Galveston, Texas 77555, United States.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D055808:Drug Discovery; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D000078183:Oxindoles; D013329:Structure-Activity Relationship; D014777:Virus Diseases / Q000188:drug therapy / Q000821:virology*; D014780:Viruses / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D007211:Indoles; D000078183:Oxindoles; C022960:2-oxindole
keywords: DENV; HIV; RSV; antiviral agents; influenza virus; spirooxindoles