Evaluation of antiherpetic compounds using a gastric cancer cell line: pronounced activity of BVDU against herpes simplex virus replication.
We developed a rapid and simple method for the screening of antiviral agents against herpes simplex virus (HSV) in a model of gastrointestinal herpetic infection in vitro. This method was based on inhibition of HSV-induced cytopathogenicity in gastric adenocarcinoma MKN-28 cells, as monitored by an MTT colorimetric assay. From the various compounds that were evaluated for their activity against HSV-1 and HSV-2, brivudine (BVDU) emerged as the most effective. When the 50% effective concentration (EC50) values of the antiherpes agents in MKN-28 cells were compared with those in human embryo lung MRC-5 cells, all compounds, except for BVDU, showed higher EC50 values in MKN-28 cells. For BVDU the EC50 values in MKN-28 cells were 0.8 (HSV-1) and 0.036 (HSV-2) times the EC50 values in MRC-5 cells. Thus BVDU was 27.5 times more active against HSV-2 in MKN-28 cells than in MRC-5 cells. The MKN-28 gastric cancer cells may be useful for the rapid screening of anti-HSV agents and, in particular, those that may be useful in therapy of gastrointestinal HSV infections in gastrointestinal herpetic infection.
Kodama
E
E
Department of Microbiology, Fukushima Medical College, Japan.
Igarashi
A
A
Mori
S
S
Hashimoto
K
K
Suzuki
T
T
De Clercq
E
E
Shigeta
S
S
D000230:Adenocarcinoma; D000998:Antiviral Agents / Q000494:pharmacology*; D001973:Bromodeoxyuridine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003124:Colorimetry; D004396:Coloring Agents; D004353:Drug Evaluation, Preclinical; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000502:physiology; D018258:Herpesvirus 2, Human / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D013274:Stomach Neoplasms; D013778:Tetrazolium Salts; D013844:Thiazoles; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D004396:Coloring Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; C020235:brivudine; C022616:thiazolyl blue; D001973:Bromodeoxyuridine