Basic dyes as inducers of interferon-like activity in mice

Diederich, J.; Lodemann, E.; Wacker, A.

doi:10.1007/bf01242639

Cited by 15 publications

(5 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This DNA intercalating activity of acridines is directly mutagenic in bacteria and viruses, explaining some of the healing effects seen in wound therapy (2,4,5). Nonetheless, in vivo studies in 1973 established that intraperitoneal injection of acriflavine resulted in the induction of an interferon (IFN)-like activity in mice sera (although IFN was not directly detected) (6). Given that acriflavine was also found to mediate the recruitment of inflammatory cells when topically used on skin (3,7), it is most likely that some of the therapeutic properties described in wound therapy also involve recruitment of the host immune response, through an unknown mechanism.…”

Section: Introductionmentioning

confidence: 99%

Activation of cGAS-dependent antiviral responses by DNA intercalating agents

et al. 2016

View full text Add to dashboard Cite

Acridine dyes, including proflavine and acriflavine, were commonly used as antiseptics before the advent of penicillins in the mid-1940s. While their mode of action on pathogens was originally attributed to their DNA intercalating activity, work in the early 1970s suggested involvement of the host immune responses, characterized by induction of interferon (IFN)-like activities through an unknown mechanism. We demonstrate here that sub-toxic concentrations of a mixture of acriflavine and proflavine instigate a cyclic-GMP-AMP (cGAMP) synthase (cGAS)-dependent type-I IFN antiviral response. This pertains to the capacity of these compounds to induce low level DNA damage and cytoplasmic DNA leakage, resulting in cGAS-dependent cGAMP-like activity. Critically, acriflavine:proflavine pre-treatment of human primary bronchial epithelial cells significantly reduced rhinovirus infection. Collectively, our findings constitute the first evidence that non-toxic DNA binding agents have the capacity to act as indirect agonists of cGAS, to exert potent antiviral effects in mammalian cells.

show abstract

Section: Introductionmentioning

confidence: 99%

Activation of cGAS-dependent antiviral responses by DNA intercalating agents

et al. 2016

View full text Add to dashboard Cite

show abstract

“…The data on the antiviral activity of toluidine blue in the scientific literature are very scanty. The mode of action of this compound was discussed, together with that of MB and other cationic dyes, by Diederich et al [ 50 , 51 ], who observed potentiation of the antiviral and IFN-inducing activities of dsRNA in L cells after exposure to such dyes. There is no detailed elucidation of this potentiated antiviral activity, but based on the fact that MB and TBO bind to RNA, an interaction of the dyes with the polyribonucleotide through intercalation was suggested [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

Photodynamic Inactivation of Bovine Coronavirus with the Photosensitizer Toluidine Blue O

Zaharieva,

Foka,

Karamichali

et al. 2023

Viruses

View full text Add to dashboard Cite

Coronaviruses (CoVs) belong to the group of enveloped positive-sense single-strand RNA viruses and are causative agents of respiratory, gastro-intestinal, and central nervous systems diseases in many host species, i.e., birds, mammals, and humans. Beta-CoVs revealed a great potential to cross the barrier between species by causing three epidemics/pandemics among humans in the 21st century. Considering the urgent need for powerful antiviral agents for decontamination, prevention, and treatment of BCoV infections, we turned our attention to the possibility of photodynamic inactivation with photosensitizers in combination with light irradiation. In the present study, we evaluated, for the first time, the antiviral activity of toluidine blue O (TBO) against Beta-coronavirus 1 (BCoV) in comparison to methylene blue (MB). First, we determined the in vitro cytotoxicity of MB and TBO on the Madin–Darby bovine kidney (MDBK) cell line with ISO10993-5/Annex C. Thereafter, BCoV was propagated in MDBK cells, and the virus titer was measured with digital droplet PCR, TCID50 assay and plaque assay. The antiviral activity of non-toxic concentrations of TBO was estimated using the direct inactivation approach. All effects were calculated in MAPLE 15® mathematical software by developing programs for non-linear modeling and response surface analysis. The median inhibitory concentration (IC50) of TBO after 72 h of incubation in MDBK cells was 0.85 µM. The antiviral activity of TBO after the direct inactivation of BCoV (MOI = 1) was significantly stronger than that of MB. The median effective concentration (EC50) of TBO was 0.005 µM. The cytopathic effect decreased in a concentration-dependent manner, from 0.0025 to 0.01 µM, and disappeared fully at concentrations between 0.02 and 0.3 µM of TBO. The number of virus particles also decreased, depending on the concentration applied, as proven by ddPCR analysis. In conclusion, TBO exhibits significant potential for direct inactivation of BCoV in vitro, with a very high selectivity index, and should be subjected to further investigation, aiming at its application in veterinary and/or human medical practice.

show abstract

“…Poly (A-U) is of special interest because it has been shown to possess a potentiated antiviral activity and an enhanced resistance to endonuclease degradation when it is thermally activated in the presence of divalent cations (Ca 2 +, Mg 2 +) (De Clercq et aI., 1971;De Clercq, 1977). Diederich et al (1972Diederich et al ( , 1973 observed that cationic dyes such as toluidine blue 0 and methylene blue also potentiate the antiviral and IFN-inducing activities of dsRNA in L cells. The basis of this potentiated antiviral activity has not been elucidated, but an interaction of the dyes with the polyribonucleotide has been suggested.…”

Section: Discussionmentioning

confidence: 99%

RNA–Intercalating Agent Interactions: in vitro Antiviral Activity Studies

Jamison

Krabill

Allen

et al. 1990

Antivir Chem Chemother

View full text Add to dashboard Cite

SummaryTwenty intercalating agents were tested to examine the effects of intercalating dye-induced perturbations upon the antiviral activity of poly (adenylate-uridylate) [poly (A-U)]. Neither poly (A-U) alone nor each intercalative dye was an efficacious antiviral agent. When poly (A-U) was combined with major groove intercalating dyes (acridine orange or proflavine), no synergism was observed. When poly (A-U) was combined with minor groove intercalating dyes [ethidium (EB), propldium (PI), adriamycin (ADR) or daunomycin (DMN)] or minor/major groove intercalating dyes [9-aminoacridine (9-AA), N 2-methyl-9-hydroxy-ellipticine (NMHE) or N 2,N6-dimethyl-9-hydroxy-ellipticine (DMHE)] the 50% effective doses (ED so ) of the poly (A-U), 9-AA, ADR, DMHE, DMN, EB, NMHE and PI decreased 18-22-60-, , , 274-,61-,154-,113-and 299-fold, respectively. When poly (A-U) was combined individually with 11 dyes whose mode of intercalation was not known, the ED so of ametantrone (HAQ), chloroquine (CHL), mitoxantrone (DHAQ) and quinine (QUI) decreased 125-,65-, 251-and 32-fold, respectively. These results suggest that the four dyes may intercalate into poly (A-U) from the minor groove. Ten (ADR, CHL, DMN, DHAQ, DMHE, EB, HAQ, NMHE, PI, QUI) of the 20 dyes evaluated exhibited significant synergism with poly (A-U), as quantified by the fractional inhibitory concentration index. Interferon (IFN) neutralization assays demonstrated that the IFN-inducing capability ofthe dye/poly (A-U) combinations approximated the sum of the capabilities of the poly (A-U) and the dyes employed. These results suggest that the majority of the dyes tested potentiate the antiviral activity of poly (A-U) without affecting the amount of IFN induced.

show abstract

Basic dyes as inducers of interferon-like activity in mice

Cited by 15 publications

References 9 publications

Activation of cGAS-dependent antiviral responses by DNA intercalating agents

Activation of cGAS-dependent antiviral responses by DNA intercalating agents

Photodynamic Inactivation of Bovine Coronavirus with the Photosensitizer Toluidine Blue O

RNA–Intercalating Agent Interactions: in vitro Antiviral Activity Studies

Contact Info

Product

Resources

About