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 gastrointestin al 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, brivu dine (BVDU) emerged as the most effective. When the 50% effective conc entration (EC(50)) values of the antiherpes agents in MKN-28 cells wer e compared with those in human embryo lung MRC-5 cells, all compounds, except for BVDU, showed higher EC(50) values in MKN-28 cells. For BVD U the EC(50) values in MKN-28 cells were 0.8 (HSV-1) and 0.036 (HSV-2) times the EC(50) values in MRC-5 cells. Thus BVDU was 275 times more active against HSV-2 in MKN-28 cells than in MRC-5 cells. The MKN-28 g astric cancer cells may be useful for the rapid screening of anti-HSV agents and, in particular, those that may be useful in therapy of gast rointestinal HSV infections in gastrointestinal herpetic infection.