In vitro inhibition of dengue virus entry by p-sulfoxy-cinnamic acid and structurally related combinatorial chemistries.
The anti-adhesive compound p-sulfoxy-cinnamic acid, zosteric acid (ZA), is derived from the temperate marine eelgrass, Zostera marina. ZA and five combinatorial chemistries based on ZA were evaluated for their anti-viral properties against dengue virus in a focus forming unit reduction assay. None of the compounds showed evidence of toxicity to the monkey kidney cell line LLCMK-2 over the concentration ranges tested. ZA showed a modest IC(50) of approximately 2.3 mM against DENV-2. Three other compounds showed IC(50) values of 2.5, 2.4, 0.3 mM, with a fourth not achieving a 50% inhibitory concentration against DENV-2. The most active compound, CF 238, showed IC(50) values of 24, 46, 14 and 47 microM against DENV-1, DENV-2, DENV-3 and DENV-4, respectively. CF 238 showed evidence of inhibition at an entry step in the viral life cycle and enhanced virus:cell binding as evidenced by a quantitative RT-PCR assay system. CF 238 may promote inappropriate virus:cell attachments common to all DENV strains that interfere with receptor interactions required for viral entry. These and other related chemistries may be useful as reagents for studying DENV entry, capturing and detecting DENV, and development of pharmaceuticals.
Rees
Craig R
CR
Biotechnology Research Group, Department of Biological Sciences, Florida Gulf Coast University, Fort Myers, FL 33965, USA. crrees@eagle.fgcu.edu
Costin
Joshua M
JM
Fink
Ryan C
RC
McMichael
Matthew
M
Fontaine
Krystal A
KA
Isern
Sharon
S
Michael
Scott F
SF
D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D002934:Cinnamates / Q000737:chemistry / Q000494:pharmacology*; D003715:Dengue / Q000188:drug therapy*; D003716:Dengue Virus / Q000187:drug effects*; D006801:Humans; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D013463:Sulfuric Acid Esters / Q000737:chemistry / Q000494:pharmacology*; D053586:Virus Internalization / Q000187:drug effects*; D035962:Zosteraceae / Q000378:metabolism
D000998:Antiviral Agents; D002934:Cinnamates; D010936:Plant Extracts; D013463:Sulfuric Acid Esters; C503399:zosteric acid