Anti-HSV activity of digitoxin and its possible mechanisms.
Herpes simplex virus type 1 (HSV-1) can establish latent infection in the nervous system and usually leads to life-threatening diseases in immunocompromised individuals upon reactivation. Treatment with conventional nucleoside analogue such as acyclovir is effective in most cases, but drug-resistance may arise due to prolonged treatment in immunocompromised individuals. In this study, we identified an in-use medication, digitoxin, which actively inhibited HSV-1 replication with a 50% effective concentration (EC(50)) of 0.05 microM. The 50% cytotoxicity concentration (CC(50)) of digitoxin is 10.66 microM and the derived selective index is 213. Several structural analogues of digitoxin such as digoxin, ouabain octahydrate and G-strophanthin also showed anti-HSV activity. The inhibitory effects of digitoxin are likely to be introduced at the early stage of HSV-1 replication and the virus release stage. The observation that digitoxin can inhibit acyclovir-resistant viruses further implicates that digitoxin represents a novel drug class with distinct antiviral mechanisms from traditional drugs.
Su
Chun-Ting
CT
Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
Hsu
John T-A
JT
Hsieh
Hsing-Pang
HP
Lin
Pi-Han
PH
Chen
Ting-Chi
TC
Kao
Chuan-Liang
CL
Lee
Chun-Nan
CN
Chang
Sui-Yuan
SY
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D004279:DNA, Viral / Q000187:drug effects / Q000235:genetics; D004074:Digitoxin / Q000737:chemistry / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D015870:Gene Expression / Q000187:drug effects; D006561:Herpes Simplex / Q000821:virology; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D006801:Humans; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics; D053586:Virus Internalization / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects; D017201:Virus Shedding / Q000187:drug effects
D000998:Antiviral Agents; D004279:DNA, Viral; D014764:Viral Proteins; D004074:Digitoxin