Epstein-Barr Virus: Inhibition of Replication by Three New Drugs

Abstract

Epstein-Barr virus (EBV) is the cause of infectious mononucleosis and is associated with three human malignancies. Acyclovir [9-(2-hydroxyethoxymethyl)guanine], the first clinically useful drug effective against replication of EBV, is without effect against latent or persistent EBV infection. Three nucleoside analogs, E-5-(2-bromovinyl)-2'-deoxyuridine, 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine, and 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-methyluracil are potent inhibitors of EBV replication in vitro. Moreover, in contrast to the reversibility of viral inhibition by Acyclovir, these three drugs have prolonged effects in suppressing viral replication even after the drugs are removed from persistently infected cell cultures.

Comparative efficacy and selectivity of some nucleoside analogs against Epstein-Barr virus

“…Although there is some evidence (4). Whether the prolonged anti-EBV activities of DHPG, FIAC, FMAU, and BVdU previously observed (14,16) are related to the accumulation of a stable pool of drug triphosphates remains to be determined. It also remains to be established whether the inhibition of EBV replication by these drugs follows a mechanism similar to that reported in herpes simplex virus (8).…”

“…(FMAU), and 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG or BW B759U), are potent inhibitors of Epstein-Barr virus (EBV) replication in vitro (14,16). These four drugs have prolonged effects in suppressing viral replication, even after the drugs are removed from persistently infected cell cultures (14,16).…”

“…These four drugs have prolonged effects in suppressing viral replication, even after the drugs are removed from persistently infected cell cultures (14,16). In the present studies we have extended our previous findings and further characterized the efficacy of each drug in parallel with acyclovir (ACV) in terms of inhibition of replication of EBV in human lymphoblastoid cell lines.…”

Potent inhibition of Epstein-Barr virus by phosphorothioate oligodeoxynucleotides without sequence specification

“…It was demonstrated previously that the ability of ACV to decrease intracellular EBV DNA copies was more readily reversible than that of DHPG (15,16). The reversibility of the anti-EBV activity of S-dC28 was examined.…”

A method for evaluating antiviral drug susceptibility of Epstein-Barr virus

“…In all instances, the EBV evaluated was in standard laboratory cell lines, most often in P3HR1 cells, clones derived from it, Raji cells superinfected with P3HR1 virus, or B95-8 cells. [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] While such information is valuable for comparing the relative effectiveness of antiviral drugs, it is a step away from assessing the actual susceptibility of patients' strains and hence cannot be used to track development of antiviral resistance. The advantage of our assay is that it can test patient-derived EBV and hence may be useful for monitoring viral resistance especially in immunocompromised hosts receiving antiviral drugs for prevention or treatment of EBV diseases.…”