The Application of Porphyrins and Their Analogues for Inactivation of Viruses

Lebedevа, N. Sh.; Gubarev, Yury A.; Koifman, Mikhail О.; Койфман, О. И.

doi:10.3390/molecules25194368

Cited by 59 publications

(38 citation statements)

References 112 publications

(193 reference statements)

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“…We expect this peculiar and unique behavior to be the result of the interaction of TMPyP4 with a specific G4 target, as proven by the essentially lower effect of TMPyP2, which parallels the compound’s lower G4 affinity [ 35 , 36 ]. At higher TMPyP4 concentration, different target/s may also become engaged [ 64 ]; because of the absence of cytotoxicity in the tested conditions, specific viral targets are still likely involved; however, an interaction between TMPyP4-stimulated viral effectors and cellular components may also be present.…”

Section: Discussionmentioning

confidence: 99%

Antiviral Activity of the G-Quadruplex Ligand TMPyP4 against Herpes Simplex Virus-1

Artusi

Ruggiero

Nadai

et al. 2021

Viruses

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The herpes simplex virus 1 (HSV-1) genome is extremely rich in guanine tracts that fold into G-quadruplexes (G4s), nucleic acid secondary structures implicated in key biological functions. Viral G4s were visualized in HSV-1 infected cells, with massive virus cycle-dependent G4-formation peaking during viral DNA replication. Small molecules that specifically interact with G4s have been shown to inhibit HSV-1 DNA replication. We here investigated the antiviral activity of TMPyP4, a porphyrin known to interact with G4s. The analogue TMPyP2, with lower G4 affinity, was used as control. We showed by biophysical analysis that TMPyP4 interacts with HSV-1 G4s, and inhibits polymerase progression in vitro; in infected cells, it displayed good antiviral activity which, however, was independent of inhibition of virus DNA replication or entry. At low TMPyP4 concentration, the virus released by the cells was almost null, while inside the cell virus amounts were at control levels. TEM analysis showed that virus particles were trapped inside cytoplasmatic vesicles, which could not be ascribed to autophagy, as proven by RT-qPCR, western blot, and immunofluorescence analysis. Our data indicate a unique mechanism of action of TMPyP4 against HSV-1, and suggest the unprecedented involvement of currently unknown G4s in viral or antiviral cellular defense pathways.

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Section: Discussionmentioning

confidence: 99%

Antiviral Activity of the G-Quadruplex Ligand TMPyP4 against Herpes Simplex Virus-1

Artusi

Ruggiero

Nadai

et al. 2021

Viruses

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“…A requirement for photo-activation of pyroPba was not investigated nor mentioned by Chen et al ( 41 ) . Porphyrins have already been described for their antiviral activity ( 25 , 42 ) . Interestingly, three photosensitizers which have been shown to be active against VSV, including N-methyl protoporphyrin IX, N-methyl mesoporphyrin IX, and Zn-protoporphyrin IX, were also identified in our screen ( 43 ) .…”

Section: Discussionmentioning

confidence: 99%

A photoactivable natural product with broad antiviral activity against enveloped viruses including highly pathogenic coronaviruses

Meunier

Desmarets

Bordage

et al. 2021

Preprint

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The SARS-CoV-2 outbreak has highlighted the need for broad-spectrum antivirals against coronaviruses (CoVs). Here, pheophorbide a (Pba) was identified as a highly active antiviral molecule against HCoV-229E after bioguided fractionation of plant extracts. The antiviral activity of Pba was subsequently shown for SARS-CoV-2 and MERS-CoV, and its mechanism of action was further assessed, showing that Pba is an inhibitor of coronavirus entry by directly targeting the viral particle. Interestingly, the antiviral activity of Pba depends on light exposure, and Pba was shown to inhibit virus-cell fusion by stiffening the viral membrane as demonstrated by cryo-electron microscopy. Moreover, Pba was shown to be broadly active against several other enveloped viruses, and reduced SARS-CoV-2 and MERS-CoV replication in primary human bronchial epithelial cells. Pba is the first described natural antiviral against SARS-CoV-2 with direct photosensitive virucidal activity that holds potential for COVID-19 therapy or disinfection of SARS-CoV-2 contaminated surfaces.

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“…Recently, these compounds have attracted interest for other areas of application, including photodynamic therapy (PDT) of skin infections, including viral [ 80 ] and other infectious diseases [ 81 ] and in the development of porphyrin nanomaterials in diagnostics and imaging [ 82 ]. The properties of porphyrins and phthalocyanines as antiviral sensitizers are mentioned in a review [ 31 ]; moreover, data on porphyrin analogs as antiviral agents are summarized in a recent focused account [ 39 ]. Most porphyrins act via type II photoinctivation through the generation of singlet oxygen, while the generation of ROS according to type I photoreactions is rather uncommon for these compounds [ 39 ].…”

Section: Porphyrins Phtalocyanins and Related Compoundsmentioning

confidence: 99%

“…There are many reports of photosensitized antiviral action of various compounds [ 31 , 34 , 35 , 36 , 37 , 38 , 39 ]. However, investigation of the mechanism of action and identification of targets for such compounds is a complicated task due to the multidisciplinarity of the problem itself.…”

Section: Introductionmentioning

confidence: 99%

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Photosensitizing Antivirals

et al. 2021

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Antiviral action of various photosensitizers is already summarized in several comprehensive reviews, and various mechanisms have been proposed for it. However, a critical consideration of the matter of the area is complicated, since the exact mechanisms are very difficult to explore and clarify, and most publications are of an empirical and “phenomenological” nature, reporting a dependence of the antiviral action on illumination, or a correlation of activity with the photophysical properties of the substances. Of particular interest is substance-assisted photogeneration of highly reactive singlet oxygen (1O2). The damaging action of 1O2 on the lipids of the viral envelope can probably lead to a loss of the ability of the lipid bilayer of enveloped viruses to fuse with the lipid membrane of the host cell. Thus, lipid bilayer-affine 1O2 photosensitizers have prospects as broad-spectrum antivirals against enveloped viruses. In this short review, we want to point out the main types of antiviral photosensitizers with potential affinity to the lipid bilayer and summarize the data on new compounds over the past three years. Further understanding of the data in the field will spur a targeted search for substances with antiviral activity against enveloped viruses among photosensitizers able to bind to the lipid membranes.

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The Application of Porphyrins and Their Analogues for Inactivation of Viruses

Cited by 59 publications

References 112 publications

Antiviral Activity of the G-Quadruplex Ligand TMPyP4 against Herpes Simplex Virus-1

Antiviral Activity of the G-Quadruplex Ligand TMPyP4 against Herpes Simplex Virus-1

A photoactivable natural product with broad antiviral activity against enveloped viruses including highly pathogenic coronaviruses

Photosensitizing Antivirals

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