Effect of Leflunomide, Cidofovir and Ciprofloxacin on replication of BKPyV in a salivary gland in vitro culture system

Jeffers-Francis, Liesl K.; Burger-Calderon, Raquel; Webster‐Cyriaque, Jennifer

doi:10.1016/j.antiviral.2015.02.002

Cited by 18 publications

(28 citation statements)

References 49 publications

(95 reference statements)

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“…To-date, it has been shown that antiviral activity against BKV is displayed by cidofovir CMY001, leflunomide, lactoferrin and ciprofloxacin. The results confirm that the latter of the aforementioned drugs has the best effect, both in vivo and in vitro [3,[10][11][12][13][14][15][16].…”

Section: Discussionsupporting

confidence: 75%

“…The necessity to look for medicines against BKV was also noted by Jeffers-Francis et al [3]. In their research, they proved that in AIDS cases BK virus may be translocated to the salivary glands where it may cause HIV-associated salivary gland disease (HIV-SGD).…”

Section: Discussionmentioning

confidence: 95%

“…The problem occurs when a person's immune system is weakened or absent [3]. Routinely used antiviral drugs, such as acyclovir, ganciclovir, ribavirin, foscarnet and cytarabine, show lack of efficacy in the treatment of polyomavirus infections [9].…”

Section: Discussionmentioning

confidence: 99%

“…In 10% of recipients of bone marrow, the BKV infection is manifested by haemorrhagic cystitis. In addition to the aforementioned direct effects, the predispositions to colorectal cancer are observed [3,4]. Along with the progress in the field of organ transplantation, including kidneys, there is a growing range of powerful immunosuppressive therapies.…”

Section: Introductionmentioning

confidence: 99%

“…One of the recommended medicines is ciprofloxacin, a synthetic antibiotic that belongs to the group of fluoroquinolones. In addition to the antiviral activity operating on the basis of the inhibition of helicase activated by the large tumour antigen (T Ag) of the BK virus, it also has antibacterial activity based on the inhibition of bacterial DNA synthesis resulting from blocking topoisomerase type II and IV [3,7].…”

Section: Introductionmentioning

confidence: 99%

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Antiviral activity of ciprofloxacin on BK virus in an in vitro culture – pilot study

Pasternak¹,

Rajtar²,

Polz‐Dacewicz³

2017

J Pre Clin Clin Res.

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Introduction. Reactivation of BKV infection caused by decrease of immunity associated with organ transplantation can lead to nephropathy and organ loss. Antiviral drugs such as ganciclovir or foscarnet did not display any activity against BK virus. A source of hope can be found in chemotherapeutics usually used in bacterial infections that inhibit the replication of viral genetic material in cells. One of the aforementioned chemotherapeutics is ciprofloxacin. The aim of the study is to evaluate the antiviral activity of ciprofloxacin against BK virus in vitro culture. Materials and method. Initially, the effects of ciprofloxacin on Vero cell viability were assessed with MTT. After determining the 3 largest non-cytotoxic concentrations of antibiotics, their effect on viral replication in cells was determined. 24-h cells culture in DMEM medium supplemented with 10% serum after 2h incubation with a 6.3 x 10 5 copies/ml infection virus were used to evaluate the effects of different concentrations of ciprofloxacin on the number of BKV copies. Quantification of BKV replication in the culture was performed by real-time PCR. Results. By means of the MTT test, the 3 largest non-cytotoxic ciprofloxacin concentrations were determined as follows: 31.25; 62.5; 125 μg/ml. Cells treated with ciprofloxacin at a concentration of 125 μg/ml display the greatest decrease in BKV replication that equaly 1.8 -3 log/5.8 -9.2 Ct, compared to the control of the virus without drugs. A decline in the number of copies of the virus was observed during the lower concentration of the antibiotic (62.5, 31.25 µg/ml) by 1.3 -2 log/4 -6.4 Ct and 0 -0.8 log/0 -2, 4 Ct, respectively. Conclusions. Ciprofloxacin exhibits antiviral activity against the BK virus by inhibiting its replication in the in vitro culture in Vero cell line.

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Antiviral activity of ciprofloxacin on BK virus in an in vitro culture – pilot study

Pasternak¹,

Rajtar²,

Polz‐Dacewicz³

2017

J Pre Clin Clin Res.

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Characterization of an in vitro model to study the possible role of polyomavirus BK in prostate cancer

Villani

Gagliano

Procacci

et al. 2018

Journal Cellular Physiology

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Prostate cancer (PCa) is the most common male neoplasms in the Western world. Various risk factors may lead to carcinogenesis, including infectious agents such as polyomavirus BK (BKPyV), which infects the human renourinary tract, establishes latency, and encodes oncoproteins. Previous studies suggested that BKPyV plays a role in PCa pathogenesis. However, the unspecific tropism of BKPyV and the lack of in vitro models of BKPyV‐infected prostate cells cast doubt on this hypothesis. The aim of the present study was to determine whether BKPyV could (a) infect normal and/or tumoral epithelial prostate cells and (b) affect their phenotype. Normal epithelial prostate RWPE‐1 cells and PCa PC‐3 cells were infected with BKPyV for 21 days. Cell proliferation, cytokine production, adhesion, invasion ability, and epithelial‐to‐mesenchymal transition (EMT) markers were analyzed. Our results show that (a) RWPE‐1 and PC‐3 cells are both infectable with BKPyV, but the outcome of the infection varies, (b) cell proliferation and TNF‐α production were increased in BKPyV‐infected RWPE‐1, but not in PC‐3 cells, (c) adhesion to matrigel and invasion abilities were elevated in BKPyV‐infected RWPE‐1 cells, and (d) loss of E‐cadherin and expression of vimentin occurred in both uninfected and infected RWPE‐1 cells. In conclusion, BKPyV may change some features of the normal prostate cells but is not needed for maintaining the transformed phenotype in the PCa cells The fact that RWPE‐1 cells exhibit some phenotype modifications related to EMT represents a limit of this in vitro model.

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Antiviral activity of A771726, the active metabolite of leflunomide, against Junín virus

Sepúlveda

Damonte

2018

Journal of Medical Virology

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The aim of this study was to investigate the effect of A771726, the active metabolite of leflunomide, (CONICET-UBA), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad against the infection with Junín virus (JUNV), agent of Argentine hemorrhagic fever (AHF). The treatment with non-cytotoxic concentrations of A771726 of Vero and A549 cells infected with JUNV inhibited virus replication in a dose-dependent manner, as determined by virus yield reduction assay. The antiviral effectiveness of A771726 was not importantly affected by the multiplicity of infection and the virus strain. Moreover, the combination of A771726 and ribavirin had a significantly more potent antiviral activity than each single drug treatment. Mechanistic studies showed that the main action of A771726 is exerted before 6 h of JUNV infection. Accordingly, inhibition of viral RNA synthesis was detected in treated infected cells by real time RT-PCR. The exogenous addition of uridine or orotic acid produced a partial reversal of the inhibitory effect of A771726 on infective virus production whereas a total reversion was detected on JUNV RNA synthesis, probably by restoration of the enzymatic activity of dihydroorotate dehydrogenase (DHODH) and the intracellular pyrimidine pools. In conclusion, these results suggest that the antiviral target would be viral RNA synthesis through pyrimidine depletion, but any other effect of the compound on JUNV infection cannot be excluded. This study opens the possibility of the therapeutic application of a wide spectrum host-targeted compound alone or in combination with ribavirin to combat AHF as well as other human pathogenic arenaviruses.

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Effect of Leflunomide, Cidofovir and Ciprofloxacin on replication of BKPyV in a salivary gland in vitro culture system

Cited by 18 publications

References 49 publications

Antiviral activity of ciprofloxacin on BK virus in an in vitro culture – pilot study

Antiviral activity of ciprofloxacin on BK virus in an in vitro culture – pilot study

Characterization of an in vitro model to study the possible role of polyomavirus BK in prostate cancer

Antiviral activity of A771726, the active metabolite of leflunomide, against Junín virus

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