Treatment of viral infections with 5-aminolevulinic acid and light

Smetana, Zehava; Malik, Zvi; Orenstein, Arie; Mendelson, Ella; Ben‐Hur, E.

doi:10.1002/(sici)1096-9101(1997)21:4<351::aid-lsm6>3.0.co;2-p

Cited by 96 publications

(54 citation statements)

References 19 publications

(19 reference statements)

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“…Since then, several attempts to discover photosensitizing drugs suitable for antimicrobial and antiviral therapies have been made. As examples, viral lesions were cleared both by ALA-PDT treatment of herpes simplex virus-infected animals and through light irradiation of cell-accumulated PPIX in an HIV-infected patient (47). Here we provide preliminary data demonstrating that noncytotoxic doses of porphyrins present antiviral activity directly on cultured cells.…”

Section: Vesicular Stomatitis Virus Inactivation By Porphyrins Antimimentioning

confidence: 77%

Mechanisms of Vesicular Stomatitis Virus Inactivation by Protoporphyrin IX, Zinc-Protoporphyrin IX, and Mesoporphyrin IX

Cruz-Oliveira

Almeida

Freire

et al. 2017

Antimicrob Agents Chemother

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Virus resistance to antiviral therapies is an increasing concern that makes the development of broad-spectrum antiviral drugs urgent. Targeting of the viral envelope, a component shared by a large number of viruses, emerges as a promising strategy to overcome this problem. Natural and synthetic porphyrins are good candidates for antiviral development due to their relative hydrophobicity and pro-oxidant character. In the present work, we characterized the antiviral activities of protoprophyrin IX (PPIX), Znprotoporphyrin IX (ZnPPIX), and mesoporphyrin IX (MPIX) against vesicular stomatitis virus (VSV) and evaluated the mechanisms involved in this activity. Treatment of VSV with PPIX, ZnPPIX, and MPIX promoted dose-dependent virus inactivation, which was potentiated by porphyrin photoactivation. All three porphyrins inserted into lipid vesicles and disturbed the viral membrane organization. In addition, the porphyrins also affected viral proteins, inducing VSV glycoprotein cross-linking, which was enhanced by porphyrin photoactivation. Virus incubation with sodium azide and ␣-tocopherol partially protected VSV from inactivation by porphyrins, suggesting that singlet oxygen ( 1 O 2 ) was the main reactive oxygen species produced by photoactivation of these molecules. Furthermore, 1 O 2 was detected by 9,10-dimethylanthracene oxidation in photoactivated porphyrin samples, reinforcing this hypothesis. These results reveal the potential therapeutic application of PPIX, ZnPPIX, and MPIX as good models for broad antiviral drug design.KEYWORDS photoactivation, porphyrin, singlet oxygen, vesicular stomatitis virus, viral inactivation D espite the increasing number of antiviral drugs available nowadays, therapeutics for viral diseases often fail due to drug resistance development by the target viruses. In the search for antiviral agents with a broad spectrum of activity against viruses, antiviral agents targeting the viral envelope, a component shared by a large number of viruses, emerge as promising compounds able to overcome the drug resistance problem. Porphyrins, amphipathic molecules able to interact with membranes, appear to be good candidates for the development of such antivirals. Porphyrins are formed by four pyrrole rings linked by methine bonds. The nitrogen atoms in the center of the ring form a pocket able to coordinate metallic ions, conferring to porphyrin the ability to absorb light at additional wavelengths and act in catalytic transformations (1). These activities allow porphyrins to be involved in important biological processes, such as respiration (heme) and photosynthesis (chlorophyll and bacteriochlorophyll) (2).

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Section: Vesicular Stomatitis Virus Inactivation By Porphyrins Antimimentioning

confidence: 77%

Mechanisms of Vesicular Stomatitis Virus Inactivation by Protoporphyrin IX, Zinc-Protoporphyrin IX, and Mesoporphyrin IX

Cruz-Oliveira

Almeida

Freire

et al. 2017

Antimicrob Agents Chemother

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“…The antiviral effect of PDT on herpes and influenza viruses in vitro [29] has been reported previously. Smetana et al [30] published a case of successful treatment of verrucae vulgares in a kidney transplant patient with 5-ALA-PDT, a disease which is associated with cutaneous HPV infection. Wierrani et al also reported the successful eradication of HPV with PDT of the cervix uteri in a limited serious of patients [19].…”

Section: Discussionmentioning

confidence: 99%

Photodynamic therapy of cervical intraepithelial neoplasia with hexaminolevulinate

Soergel

Wang²,

Stepp³

et al. 2008

Lasers Surg Med

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“…Using electron microscopy, a massive destruction of virus envelopes was detected after treatment with phthalocyanines containing metal ligands, leading to a significant decrease of virus infectivity of several enveloped viruses [Varicella zoster virus (VZV), HSV-1 and HSV-2], whereas non-enveloped adenovirus was largely resistant to the treatment (Smetana et al 1994). Nevertheless, several studies have presented evidence that non-enveloped viruses are also sensitive to direct PACT inactivation (Kasturi and Platz 1992;Gaspard et al 1995;Costa et al 2008Costa et al , 2010Zupan et al 2008), which might be explained by photoactivated protein crosslinking that leads to direct damage or loss of proteins, and finally the loss of infectivity (Lenard et al 1993;Smetana et al 1997;Orosz et al 2013). At physiological conditions, non-enveloped viruses have negatively charged capsids and enveloped viruses harbour negatively charged glycoproteins on their surface, and are thus likely directly targeted by cationic porphyrins via electrostatic interactions, like previously described for Gram(−) bacteria (Karlin and Brendel 1988;Michen and Graule 2010;Liu et al 2015).…”

Section: Molecular Targets Of Antiviral Pactmentioning

confidence: 99%

Porphyrin-based cationic amphiphilic photosensitisers as potential anticancer, antimicrobial and immunosuppressive agents

2017

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Photodynamic therapy (PDT) combines a photosensitiser, light and molecular oxygen to induce oxidative stress that can be used to kill pathogens, cancer cells and other highly proliferative cells. There is a growing number of clinically approved photosensitisers and applications of PDT, whose main advantages include the possibility of selective targeting, localised action and stimulation of the immune responses. Further improvements and broader use of PDT could be accomplished by designing new photosensitisers with increased selectivity and bioavailability. Porphyrin-based photosensitisers with amphiphilic properties, bearing one or more positive charges, are an effective tool in PDT against cancers, microbial infections and, most recently, autoimmune skin disorders. The aim of the review is to present some of the recent examples of the applications and research that employ this specific group of photosensitisers. Furthermore, we will highlight the link between their structural characteristics and PDT efficiency, which will be helpful as guidelines for rational design and evaluation of new PSs.

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Treatment of viral infections with 5-aminolevulinic acid and light

Cited by 96 publications

References 19 publications

Mechanisms of Vesicular Stomatitis Virus Inactivation by Protoporphyrin IX, Zinc-Protoporphyrin IX, and Mesoporphyrin IX

Mechanisms of Vesicular Stomatitis Virus Inactivation by Protoporphyrin IX, Zinc-Protoporphyrin IX, and Mesoporphyrin IX

Photodynamic therapy of cervical intraepithelial neoplasia with hexaminolevulinate

Porphyrin-based cationic amphiphilic photosensitisers as potential anticancer, antimicrobial and immunosuppressive agents

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