The Effect of Tilorone Hydrochloride on the Growth of Several Animal Viruses in Tissue Cultures

Katz, Ehud; Margalith, Eva; Winer, Bela

doi:10.1099/0022-1317-31-1-125

Cited by 12 publications

(7 citation statements)

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“…Tilorone has a track record of safe use in children and adults for~20 years as both a prophylaxis and treatment for viral diseases. The drug has been produced and manufactured at the kiloton (1000 kg) scale and can be produced at a very low cost per dose based on the current list price (11).In vivo efficacy studies from the literature support possible uses of tilorone against a broad array of infections including influenza A, influenza B, herpes simplex virus 1, West Nile virus, Mengo virus, Semliki Forest virus, vesicular stomatitis virus, encephalomyocarditis virus (12)(13)(14)(15)(16)(17) and more recently against human coronaviruses including MERS-CoV (18) (Table I).…”

Section: Introductionmentioning

confidence: 99%

Tilorone: a Broad-Spectrum Antiviral Invented in the USA and Commercialized in Russia and beyond

2020

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Section: Introductionmentioning

confidence: 99%

Tilorone: a Broad-Spectrum Antiviral Invented in the USA and Commercialized in Russia and beyond

2020

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“…Others have suggested that tilorone does not induce interferon in humans and therefore may have different activities in different species (24). The antiviral activity of tilorone has been reported against a broad-spectrum array of viruses, including herpes simplex virus (21,25,26), influenza A and B virus (21,27), Venezuelan equine encephalitis virus (28), Mengo virus (21), Semliki Forest virus (21,26,29), vesicular stomatitis virus (21,22), and West Nile virus (30). Human clinical studies outside the United States have evaluated tilorone as a treatment for acute respiratory viral infections (ARVIs), where it demonstrated significantly improved patient outcomes (24,(31)(32)(33).…”

mentioning

confidence: 99%

Efficacy of Tilorone Dihydrochloride against Ebola Virus Infection

Ekins

Lingerfelt

Comer

et al. 2018

Antimicrob Agents Chemother

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Tilorone dihydrochloride (tilorone) is a small-molecule, orally bioavailable drug that is used clinically as an antiviral outside the United States. A machinelearning model trained on anti-Ebola virus (EBOV) screening data previously identified tilorone as a potent in vitro EBOV inhibitor, making it a candidate for the treatment of Ebola virus disease (EVD). In the present study, a series of in vitro ADMET (absorption, distribution, metabolism, excretion, toxicity) assays demonstrated the drug has excellent solubility, high Caco-2 permeability, was not a P-glycoprotein substrate, and had no inhibitory activity against five human CYP450 enzymes (3A4, 2D6, 2C19, 2C9, and 1A2). Tilorone was shown to have 52% human plasma protein binding with excellent plasma stability and a mouse liver microsome half-life of 48 min. Dose range-finding studies in mice demonstrated a maximum tolerated single dose of 100 mg/kg of body weight. A pharmacokinetics study in mice at 2-and 10-mg/kg dose levels showed that the drug is rapidly absorbed, has dosedependent increases in maximum concentration of unbound drug in plasma and areas under the concentration-time curve, and has a half-life of approximately 18 h in both males and females, although the exposure was ϳ2.5-fold higher in male mice. Tilorone doses of 25 and 50 mg/kg proved efficacious in protecting 90% of mice from a lethal challenge with mouse-adapted with once-daily intraperitoneal (i.p.) dosing for 8 days. A subsequent study showed that 30 mg/kg/day of tilorone given i.p. starting 2 or 24 h postchallenge and continuing through day 7 postinfection was fully protective, indicating promising activity for the treatment of EVD.

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“…It is the first recognized synthetic, low-molecular-weight compound that is an orally active interferon inducer, and is also reported to have anti-neoplastic and anti-inflammatory actions [79,80,81,82]. Tilorone hydrochloride has been shown to inhibit HSV-1 and vaccinia at concentrations of 10 μg/mL [83,84,85]. The researchers noted that the adsorption of the virus was not affected by the drug, and the penetration of the deoxyribonucleic acid of the input virus into the cytoplasm and nuclei proceeded normally when tilorone hydrochloride was present.…”

Section: Resultsmentioning

confidence: 99%

Antiviral Activity of Metal-Containing Polymers—Organotin and Cisplatin-Like Polymers

et al. 2011

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Polymers containing platinum and to a lesser extent tin, have repeatedly demonstrated antitumor activity in vitro and in vivo against a variety of cell and tumor types. The mechanisms responsible for the antitumor activity include inducing a delay in cell proliferation and sister chromatid exchanges blocking tumor growth. As most DNA and some RNA viruses require, and even induce, infected cells to initiate DNA replication and subsequent cell division, compounds with antitumor activity will very likely also possess antiviral activity. This article examines the use of metal-containing polymers as a novel class of antivirals.

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The Effect of Tilorone Hydrochloride on the Growth of Several Animal Viruses in Tissue Cultures

Cited by 12 publications

References 0 publications

Tilorone: a Broad-Spectrum Antiviral Invented in the USA and Commercialized in Russia and beyond

Tilorone: a Broad-Spectrum Antiviral Invented in the USA and Commercialized in Russia and beyond

Efficacy of Tilorone Dihydrochloride against Ebola Virus Infection

Antiviral Activity of Metal-Containing Polymers—Organotin and Cisplatin-Like Polymers

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