Structure-Activity Relationship Study of QL47: A Broad-Spectrum Antiviral Agent.
Here we report the structure-activity relationship (SAR) investigations of QL-XII-47 (QL47), a compound that possesses broad-spectrum antiviral activity against dengue virus and other RNA viruses. A medicinal chemistry campaign initiated from QL47, a previously reported covalent BTK inhibitor, to derive YKL-04-085, which is devoid of any kinase activity when screened against a panel of 468 kinases and with improved pharmacokinetic properties. Both QL47 and YKL-04-085 are potent inhibitors of viral translation and exhibit cellular antiviral activity at 35-fold lower concentrations relative to inhibition of host-cell proliferation.
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, United States; Departments of Biological Chemistry & Molecular Pharmacology and Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115, United States.
Yanke
Y
Liang
Departments of Biological Chemistry & Molecular Pharmacology and Microbiology and Immunobiology, Harvard Medical School , Boston, Massachusetts 02115, United States.
Melissanne
M
de Wispelaere
Departments of Biological Chemistry & Molecular Pharmacology and Microbiology and Immunobiology, Harvard Medical School , Boston, Massachusetts 02115, United States.
Margot
M
Carocci
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, United States; Departments of Biological Chemistry & Molecular Pharmacology and Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115, United States.
Qingsong
Q
Liu
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, United States; Departments of Biological Chemistry & Molecular Pharmacology and Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115, United States.
Jinhua
J
Wang
Departments of Biological Chemistry & Molecular Pharmacology and Microbiology and Immunobiology, Harvard Medical School , Boston, Massachusetts 02115, United States.
Priscilla L
PL
Yang
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, United States; Departments of Biological Chemistry & Molecular Pharmacology and Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115, United States.
Nathanael S
NS
Gray
Dengue virus; QL47; broad-spectrum antiviral; structure−activity relationship