Antiviral Activity of Cytarabine in Herpesvirus–Infected Rats

Abstract

Intranasal inoculation of herpesvirus (approximately 1.8 mean lethal doses [LD 50 ] in 0.1 ml) into 105- to 115-g rats produces paralytic disease in 4 to 5 days and 80 to 100% mortality in 8 to 12 days. Cytarabine (ara-C) (40 to 320 mg/kg), administered subcutaneously to inoculated rats, delays the onset of paralysis and protects the animals from death. Drug treatments were given twice daily for 5 days. Beneficial drug effects were observed even when initiation of therapy was delayed for 3 days after virus inoculation. A dose-response relationship existed when therapy was initiated at 4 h after virus inoculation. However, when therapy was delayed for 3 days, it appeared that the highest drug level (320 mg/kg twice daily) was somewhat less effective than the lower doses (160 and 80 mg/kg twice daily). Virus could be detected in homogenates of brain beginning 3 days after inoculation, and the titer increased through 7 days. Ara-C treatment, initiated 4 h after inoculation, caused a delay in the appearance of virus, and a reduction in the titer in the brain homogenates. No virus was detected in blood serum, or in homogenates prepared from lung, kidney, thymus, or spleen of infected rats. The virus titration studies are in agreement with the illness and mortality produced by herpesvirus infection.

Human Herpesvirus 8 Open Reading Frame 21 Is a Thymidine and Thymidylate Kinase of Narrow Substrate Specificity That Efficiently Phosphorylates Zidovudine but Not Ganciclovir

“…It is also possible that another viral gene product, such as ORF 36, the virus phosphotransferase homologue of human CMV UL97, can phosphorylate GCV and be responsible for its activity in vivo (4). Alternatively, because of GCV superior toxicity, preferential uptake into rapidly growing tumor cells and conversion by cellular enzymes may create a situation where GCV acts as a chemotherapeutic reagent, similar to other nucleoside analogs, such as cytosine arabinofuranoside and adenine arabinofuranoside, that have both antiviral and chemotherapeutic activity (1,35,37,50).…”

Herpesvirus hominis Infection in Newborn Mice: Comparison of the Therapeutic Efficacy of 1-β- d -Arabinofuranosylcytosine and 9-β- d -Arabinofuranosyladenine

“…Renis (28) demonstrated that ara-C treatment of rats inoculated intranasally with herpesvirus delayed the onset of paralysis and death, reduced final mortality, and delayed and suppressed viral replication in brain tissue. corneal scarification method and treated with ara-C. ara-A has been shown to be effective in the treatment of HVH keratitis (30) and subsequent encephalitis (29) in hamsters.…”

Novel Method for Detection of Genes With Altered Expression Caused by Coronavirus Infection and Screening of Candidate Drugs for SARS-CoV-2

“…Myelocytomatosis virus is a retrovirus, which is an enveloped, negative-sense, single-stranded RNA virus, whereas Rous sarcoma virus is an enveloped, positive-sense, single-stranded RNA virus. Although there are no studies showing that cytarabine is effective against infection of an RNA virus, one report demonstrated that cytarabine can affect DNA virus infection [12]. Pyrogallol was reported to have anti-virus effects on human influenza virus strain A/Udorn/72, avian influenza virus A/swan/Shimane/499/83, herpes simplex virus-1, vesicular stomatitis virus, and retrovirus [13].…”