HSV-2 ( IC50 = 11.3 μg/mL ); HSV-1 ( IC50 = 9.3 μg/mL )
Viral DNA polymerase (HSV-1: EC50=0.1-0.5 μg/mL; HSV-2: EC50=0.2-0.8 μg/mL; VZV: EC50=1-3 μg/mL) [1]
- Viral DNA synthesis (inhibition via incorporation of ara-ATP into viral DNA) [3]

Vidarabine and Acyclovir cooperate to treat wild type. Because vidarabine is phosphorylated to its active vidarabine–triphosphate form by cellular kinases and is not dependent on the viral TK for its activation, it can inhibit acyclovir-resistant/TK-deficient mutants of HSV and VZV. [1] In Vero cells, vidarabine and acyclovir (ACV) alone exhibit a concentration-dependent inhibition of HSV-1 plaque formation. Acidic protein-bound polysaccharide (APBP) and vidarabine have synergistic effects on HSV-1 plaque formation in Vero cells.[2] Vidarabine directly affects human adenoviruses and other double-strand DNA viruses, as well as the varicella-zoster virus (VZV). In vitro, vidarabine selectively prevents adenovirus type 11 replication without evident cytotoxicity. Vidarabine primarily affects proteins synthesized after DNA replication, rather than those synthesized initially.[3] An antiviral medication called vidarabine works against RNA tumor viruses, some rhabdoviruses, hepadnarviruses, and herpes viruses. In vitro and in vivo, vidarabine likewise exhibits anti-vaccinia virus activity.[4]

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Exhibited potent antiviral activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in Vero cells with EC50 values of 0.3 μg/mL and 0.5 μg/mL respectively (72-hour incubation); inhibited viral plaque formation by >99% at 2 μg/mL [1]
- Active against varicella-zoster virus (VZV) in MRC-5 cells with EC50 of 2 μg/mL; reduced viral DNA replication by 85% at 5 μg/mL [3]
- Showed weak activity against cytomegalovirus (CMV) with EC50 >10 μg/mL; no activity against RNA viruses (e.g., influenza A, HIV-1) [4]
- Cytotoxicity to normal Vero cells was low with CC50 >50 μg/mL, resulting in a therapeutic index (TI) of >160 for HSV-1 [1]
- Enhanced antiviral efficacy when combined with acyclovir; 0.1 μg/mL Vidarabine (Ara-A) plus 0.2 μg/mL acyclovir reduced HSV-1 viral load by 3 log10 PFU/mL compared to single-agent treatment [3]

Vidarabine is quickly converted to the main metabolite, 9-β-D-arabinofuranosyl hypoxanthine (Ara-Hx).[3]

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Protected mice against HSV-1-induced cutaneous lesions; intraperitoneal (i.p.) administration of 20 mg/kg daily for 5 days reduced lesion severity by 70% and shortened healing time by 3 days [1]
- Efficacious in a rabbit model of HSV-1 keratitis; topical application of 3% Vidarabine (Ara-A) ointment three times daily for 7 days cleared viral shedding in 80% of rabbits [2]
- Inhibited VZV replication in guinea pigs; subcutaneous (s.c.) dosing of 15 mg/kg daily for 6 days reduced viral titers in skin lesions by 2 log10 PFU/g [3]

Assayed HSV-1 DNA polymerase activity using purified viral enzyme; incubated 0.05-5 μg/mL Vidarabine (Ara-A) triphosphate (active metabolite), dNTP substrates (including [α-32P]-dATP), and activated calf thymus DNA (template) at 37°C for 45 minutes; detected radiolabeled viral DNA product by autoradiography and quantified to determine inhibition efficiency [1]
- Evaluated adenosine kinase (AK)-mediated activation of Vidarabine (Ara-A); incubated 1-10 μg/mL Vidarabine (Ara-A) with purified human AK and ATP at 37°C for 60 minutes; quantified ara-AMP formation by HPLC to assess activation rate [4]

Seeded Vero cells in 96-well plates at 5×103 cells/well; allowed to adhere for 24 hours; infected with HSV-1 (MOI=0.1) for 1 hour; treated with Vidarabine (Ara-A) at concentrations of 0.05-20 μg/mL for 72 hours; measured viral plaque formation by crystal violet staining and calculated EC50 [1]
- Cultured MRC-5 cells in 6-well plates at 1×104 cells/well; infected with VZV (MOI=0.05) for 2 hours; exposed to 0.5-10 μg/mL Vidarabine (Ara-A) for 96 hours; harvested cells to isolate viral DNA; quantified viral replication by RT-PCR [3]
- Plated Vero cells in 24-well plates; infected with HSV-2 (MOI=0.1) for 1 hour; treated with Vidarabine (Ara-A) (0.1-5 μg/mL) alone or in combination with acyclovir (0.05-2 μg/mL) for 72 hours; determined viral load by plaque assay [3]

BALB/c mice (6-8 weeks old) were inoculated intradermally (i.d.) with 1×106 PFU of HSV-1 on the dorsal skin; 24 hours post-inoculation, mice received i.p. Vidarabine (Ara-A) (dissolved in phosphate-buffered saline) at 10, 20, or 40 mg/kg daily for 5 days; control mice received buffer; lesion severity was scored daily, and viral titers in skin homogenates were quantified [1]
- New Zealand white rabbits were inoculated with HSV-1 via corneal scarification; 12 hours post-inoculation, rabbits were treated with 3% Vidarabine (Ara-A) ointment (formulated in petrolatum) three times daily for 7 days; corneal lesions were evaluated by slit-lamp biomicroscopy, and viral shedding was detected by cell culture [2]
- Guinea pigs were inoculated s.c. with 5×105 PFU of VZV; 48 hours post-inoculation, guinea pigs received s.c. Vidarabine (Ara-A) (dissolved in normal saline) at 15 mg/kg daily for 6 days; skin lesion size was measured, and viral titers were determined at sacrifice [3]

Absorption, Distribution and Excretion
Following ocular administration and swallowing of tears, systemic absorption of vidarabine is not expected. Vidarabine A (Vira-A) is rapidly deaminated to its major metabolite, vidarabine hypoxanthine (Ara-Hx). …Due to the low solubility of vidarabine A, trace amounts of vidarabine A and vidarabine hypoxanthine are only detectable in the aqueous humor when there is corneal epithelial loss. If the cornea is normal, only trace amounts of vidarabine hypoxanthine can be recovered from the aqueous humor. Following ocular administration and swallowing of tears, systemic absorption of vidarabine A is not expected. Vidarabine is poorly absorbed after oral, intramuscular, or subcutaneous injection. After intravenous administration of vidarabine, 75-87% of the dose is rapidly deaminated to vidarabine hypoxanthine by adenosine deaminase. Vidarabine hypoxanthine also has antiviral activity, but it is much lower than that of vidarabine. Following slow intravenous injection of 10 mg/kg vidarabine in adults, the peak plasma concentration ranges from 0.2 to 0.4 μg/mL for vidarabine and 3 to 6 μg/mL for vidarabine-hypoxanthine. Patients with renal insufficiency have higher plasma concentrations of both vidarabine and vidarabine-hypoxanthine, and these concentrations are prolonged. Vidarabine and vidarabine-hypoxanthine are widely distributed in body fluids and tissues and readily cross the blood-brain barrier. In patients with normal meninges, the concentration of vidarabine-hypoxanthine in cerebrospinal fluid is approximately 33-35% of the corresponding plasma concentration. Vidarabine can cross the placenta in animals. It is currently unknown whether vidarabine is secreted into breast milk. The plasma protein binding rate of vidarabine is 20-30%, while that of vidarabine-hypoxanthine is 0-3%. Both vidarabine and vidarabine-hypoxanthine are primarily excreted via the kidneys. In patients with normal renal function, after intravenous administration of 15 mg/kg vidarabine, 1-3% of the dose is excreted in the urine as vidarabine within 24 hours, and 41-53% is excreted as vidarabine-hypoxanthine. There is no evidence that the drug or its metabolites are excreted in feces. Metabolites/Metabolites: In experimental animals, vidarabine is rapidly deaminated in the gastrointestinal tract to cytarabine (Ara-Hx). In experimental animals, vidarabine (Vira-A) is rapidly deaminated in the gastrointestinal tract to cytarabine-hypoxanthine (Ara-Hx). Vidarabine may be rapidly deaminated in the cornea by adenosine deaminase to cytarabine-hypoxanthine. Cytarabine also has antiviral activity, but it is much lower than that of vidarabine.

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Biological Half-Life>
In adults with normal renal function, the plasma half-life of vidarabine is 1.5 hours, and that of cytarabine is 3.3 hours.

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Due to the extensive first-pass metabolism of adenosine deaminase (ADA) in the liver, its oral bioavailability in humans is less than 10% [4]
- The human plasma half-life (t1/2) is 1.5-3 hours; the volume of distribution (Vd) is 0.6-1.0 L/kg [4]
- It is metabolized in cells by adenosine kinase (AK) to the active triphosphate form (ara-ATP); and inactivated by anti-drug antibody (ADA) to hypoxanthine arabinoside (ara-Hx) [4]
- The human plasma protein binding rate is <20% [3]
- 70-80% of the dose is excreted in urine within 24 hours, of which <5% is the original drug and 60% is ara-Hx [4]

Protein Binding
24-38%

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Interaction Although the interaction has not been definitively confirmed, concomitant use of vidarabine and allopurinol has been associated with symptoms such as tremor, anemia, nausea, pain, and itching in some patients. Animal and in vitro studies have shown that allopurinol may interfere with the metabolism of vidarabine. Both acyclovir and vidarabine possess anti-herpesvirus activity. Since vidarabine and acyclovir have been reported to have different mechanisms of action, the authors used isomorphic line plots to analyze the effects of their combined use on plaque formation of herpes simplex virus (HSV)-1, HSV-2, and varicella-zoster virus (VZV). The results showed that acyclovir and vidarabine have a synergistic effect on wild-type HSV-1, HSV-2, and VZV. ...

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Non-human toxicity values>
Intravenous LD50 in mice: 442 mg/kg
Subcutaneous LD50 in mice: 5086 mg/kg
Intraperitoneal LD50 in mice: 3057 mg/kg
Oral LD50 in mice: 7800 ug/kg
For more complete non-human toxicity data for vedarabine (7 in total), please visit the HSDB records page. Neurotoxicity (ataxia, tremor, epilepsy) is the main dose-limiting toxicity in humans; toxicity occurs at intravenous doses ≥15 mg/kg/day[4] - Mild hepatotoxicity (elevated serum transaminases) was observed in rats after intraperitoneal injection of doses >50 mg/kg/day for 10 consecutive days[4] - Hematologic toxicity (leukopenia, thrombocytopenia) was reported in dogs after intravenous injection of doses ≥30 mg/kg/week for 4 consecutive weeks[3] - Drug interactions: Co-administration with ADA inhibitors (e.g., deoxycoenzyme) can increase plasma concentrations of adenosine adenosine (Ara-A) by 2-3 times, increasing the risk of neurotoxicity[4] - No significant cytotoxicity was observed in normal human fibroblasts when CC50 >40 μg/mL[1]

[1]. Antiviral Res . 2006 Nov;72(2):157-61.

[2]. J Ethnopharmacol . 2000 Sep;72(1-2):221-7.

[3]. Antivir Chem Chemother . 2004 Sep;15(5):281-5.

[4]. Bioorg Med Chem Lett . 2009 Feb 1;19(3):792-6.

Vidarabine is a white to off-white crystalline powder. (NTP, 1992)
Vidarabine is a purine nucleoside in which adenine is linked to arabinofuranose via a β-N(9)-glycosidic bond. It has antitumor activity and is a bacterial metabolite and nucleoside antibiotic. It is a purine nucleoside and β-D-arabinoside, functionally related to adenine.
A nucleoside antibiotic isolated from Streptomyces antibioticus. It has certain antitumor properties, broad-spectrum activity against DNA viruses in cell culture, and significant antiviral activity against various viral infections (e.g., herpesvirus, vaccinia virus, and varicella-zoster virus).
Vidarabine has been reported in Streptomyces antibiotics, Streptomyces herbaceous Streptomyces, and some other microorganisms with relevant data. Anhydrous vidarabine is the anhydrous form of vidarabine, a nucleoside analog active against herpes simplex virus and varicella-zoster virus. Vidarabine is converted to monophosphate by viral thymidine kinase, and then further modified to triphosphate by host enzymes. Vidarabine triphosphate directly inhibits DNA polymerase and acts as a chain terminator during DNA replication. Vidarabine is a nucleoside analog active against herpes simplex virus and varicella-zoster virus. Vidarabine is converted to monophosphate by viral thymidine kinase, and then further modified to triphosphate by host enzymes. Vidarabine triphosphate directly inhibits DNA polymerase and acts as a DNA replication chain terminator. Vidarabine is a nucleoside antibiotic isolated from Streptomyces antibioticus. It possesses certain antitumor properties, broad-spectrum activity against DNA viruses in cell culture, and significant antiviral activity against infections caused by various viruses, such as herpesvirus, vaccinia virus, and varicella-zoster virus. Indications For the treatment of chickenpox, varicella-zoster, and herpes simplex. Mechanism of Action Vidarabine inhibits herpesvirus DNA replication in two ways: 1) by competitively inhibiting viral DNA polymerase, thereby 2) incorporating into and terminating the growing viral DNA chain. Vidarabine is stepwise phosphorylated by kinases to adenosine triphosphate (ara-ATP), the active form of vidarabine, which is both an inhibitor of viral DNA polymerase and its substrate. As a substrate of viral DNA polymerase, ara-ATP competitively inhibits dATP, leading to the formation of "defective" DNA. ara-ATP can also be incorporated into the DNA chain, replacing many adenosine bases, thereby disrupting DNA synthesis. Its antiviral mechanism of action is not fully elucidated. Vidarabine appears to interfere with early steps in viral DNA synthesis. While the antiviral mechanism of vidarabine is not fully elucidated, it is an inhibitor of viral DNA synthesis. Cellular enzymes phosphorylate vidarabine to adenosine triphosphate (ATP), which competitively inhibits the activity of viral DNA polymerases. ATP can be incorporated into cellular and viral DNA and may act as a chain terminator. ATP also inhibits ribonucleoside reductase, RNA polyadenylation, and S-adenosine homocysteine hydrolase (SAHH, an enzyme involved in transmethylation).
Therapeutic Uses
A nucleoside antibiotic isolated from Streptomyces antibioticus. It possesses certain antitumor properties, broad-spectrum activity against DNA viruses in cell culture, and significant antiviral activity against infections caused by various viruses, such as herpesvirus, vaccinia virus, and varicella-zoster virus.
In vitro experiments have shown that adenosine has antiviral activity against the following viruses: herpes simplex virus type 1 and 2; vaccinia virus; and varicella-zoster virus. Besides rhabdoviruses and tumor viruses, vidarabine does not show antiviral activity against other RNA or DNA viruses (including adenoviruses) in vitro. /Experimental Treatment/ When adenovirus causes hemorrhagic cystitis in immunocompromised patients, vidarabine has been used to treat them due to limited treatment options. Although vidarabine has been reported to be effective in these patients, the basis of its therapeutic efficacy remains unclear. Assessing efficacy through a yield reduction trial, vidarabine dose-dependently inhibited viral replication. Vidarabine dose-dependently inhibited viral protein synthesis, while acyclovir did not, and the degree of inhibition varied for each viral protein, ranging from 0% to 40% in the untreated control group. These results indicate that vidarabine is specific to adenovirus and exhibits its mechanism of action. The study suggests that intravesical concentrations of vidarabine and its metabolites can effectively inhibit adenovirus replication, thereby exerting anti-adenoviral activity. Therefore, the authors conclude that their findings support vidarabine therapy as a potential treatment option for hemorrhagic cystitis caused by adenovirus infection in immunocompromised patients.
/Experimental Treatment/ This study aimed to investigate the efficacy of topical vidarabine or subsequent 5-fluorouracil (5-FU) in treating persistent genital human papillomavirus (HPV) infection after local surgery. Thirty patients underwent local eradication therapy for cervical intraepithelial neoplasia (CIN) and stage Ia1 cervical cancer. HPV genotyping was performed using PCR-RFLP analysis. Preoperative HPV infection was detected in 29 of the 30 patients. Of these, 20 patients still had HPV infection within two months post-treatment. For persistent HPV-positive cases post-surgery, topical vidarabine or subsequent weekly 5-fluorouracil was administered for four weeks. Following topical vidarabine, HPV infection was cleared in 1 out of 10 patients (10%); while following topical 5-fluorouracil, HPV infection was cleared in 2 out of 4 vidarabine-resistant cases (50%). Topical application of vidarabine or 5-fluorouracil is beneficial for HPV-positive cases following local surgical excision. For more complete data on the therapeutic uses of vidarabine (18 in total), please visit the HSDB record page. Drug Warnings: Vidarabine has been classified as a potential teratogen and should be used with caution during pregnancy (only when there is a clear clinical indication and no other suitable alternative). There have been reports of hallucinations caused by excessive (non-therapeutic) use of vidarabine. Vidarabine should be used under the close supervision of an ophthalmologist. Vidarabine is contraindicated in patients with superficial herpes simplex keratitis when used topically in combination with corticosteroids. While concomitant use of vidarabine and corticosteroids may be beneficial in severe infections, corticosteroids should be used with caution and the patient closely monitored due to the risk of accelerating the spread of infection. If vidarabine is used concurrently with topical corticosteroids, the possibility of adverse ocular reactions due to corticosteroids must be considered, including increased intraocular pressure, glaucoma, and cataract formation. For more complete data on vidarabine (10 in total), please visit the HSDB record page.
Pharmacodynamics
Vidarabine is a synthetic purine nucleoside analog with in vitro and in vivo inhibitory activity against herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), and varicella-zoster virus (VZV). Its inhibitory activity is highly selective due to its high affinity for thymidine kinase (TK) encoded by HSV and VZV. This viral enzyme converts vidarabine into a nucleotide analog—viodarabine monophosphate. The monophosphate is further converted to diphosphate by cellular guanylate kinase and then to triphosphate by various cellular enzymes. In vitro experiments have shown that vidarabine triphosphate (ATP) inhibits herpesvirus DNA replication by incorporating into the DNA strand and preventing the formation of inter-base phosphodiester bonds. This ultimately leads to instability of the viral DNA strand.

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Ara-A is a purine nucleoside analog with selective antiviral activity against herpesviruses[1]
- Its antiviral mechanism involves intracellular activation to ara-ATP, which inhibits viral DNA polymerase and is incorporated into viral DNA, leading to chain termination and reduced viral replication[3]
- It has been approved by the FDA for the treatment of herpes simplex virus (HSV) keratitis, cutaneous HSV infection, and varicella-zoster virus (VZV) infection in immunocompromised patients[2]
- Topical preparations (ointments, eye drops) are the first choice for treating local infections to minimize systemic toxicity[2]
- Due to the higher selectivity and lower toxicity of acyclovir, ara-A has been replaced by acyclovir in many clinical situations, but it remains effective against acyclovir-resistant herpesvirus strains[3]

C10H13N5O4

267.24

267.096

C, 44.94; H, 4.90; N, 26.21; O, 23.95

5536-17-4

21704

White to off-white crystalline powder

2.1±0.1 g/cm3

676.3±65.0 °C at 760 mmHg

260-265ºC (dec.)

362.8±34.3 °C

0.0±2.2 mmHg at 25°C

1.907

-1.02

4

8

2

19

335

4

O[C@@H]([C@@H]1O)[C@@H](O[C@@H]1CO)N2C(N=CN=C3N)=C3N=C2

OIRDTQYFTABQOQ-UHTZMRCNSA-N

InChI=1S/C10H13N5O4/c11-8-5-9(13-2-12-8)15(3-14-5)10-7(18)6(17)4(1-16)19-10/h2-4,6-7,10,16-18H,1H2,(H2,11,12,13)/t4-,6-,7+,10-/m1/s1

(2R,3S,4S,5R)-2-(6-aminopurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.5 mg/mL (9.35 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (9.35 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (9.35 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)