Discovery of anti-varicella zoster virus activity of polyether antibiotic CP-44161.
In search for new anti-varicella zoster virus (VZV) compounds with new mechanism of action, we applied a DNA hybridization assay (dot blot method) for screening. Using this method, we screened microbial products and found the polyether compound CP-44161 from the culture broth of an actinomycete strain. CP-44161 was previously reported as an anticoccidal agent, but there has been no claim of its antiviral activities. CP-44161 showed strong anti-VZV activity against pOka strain by plaque reduction assay. Moreover, CP-44161 showed lower cytotoxicity than other antiviral polyethers, such as monensin and nigericin. Its better safety margin and strong anti-VZV properties make it a good candidate for a new anti-VZV agent.
Yamagishi
Yukiko
Y
Fermentation Research Labs, Astellas Pharma Inc., Tsukuba-shi, Ibaraki, Japan. yukiko.yamagishi@jp.astellas.com
Ueno
Chihoko
C
Kato
Akemi
A
Kai
Hirohito
H
Sasamura
Hiromi
H
Ueno
Motoi
M
Sato
Bunji
B
Fujie
Akihiko
A
Fujii
Takashi
T
Hino
Motohiro
M
Tsujii
Eisaku
E
D000192:Actinomycetales / Q000737:chemistry / Q000145:classification / Q000378:metabolism; D000998:Antiviral Agents / Q000494:pharmacology*; D001952:Bridged-Ring Compounds; D002240:Carbohydrate Sequence; D045744:Cell Line, Tumor; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004279:DNA, Viral / Q000737:chemistry / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004987:Ethers; D005285:Fermentation; D005663:Furans / Q000494:pharmacology*; D014645:Herpesvirus 3, Human / Q000187:drug effects*; D006801:Humans; D015151:Immunoblotting; D007202:Indicators and Reagents; D008969:Molecular Sequence Data; D011714:Pyrans / Q000494:pharmacology*
D000998:Antiviral Agents; D001952:Bridged-Ring Compounds; C425408:CP44,161; D004279:DNA, Viral; D004987:Ethers; D005663:Furans; D007202:Indicators and Reagents; D011714:Pyrans