A Novel Class of
            <i>meso</i>
            -Tetrakis-Porphyrin Derivatives Exhibits Potent Activities against Hepatitis C Virus Genotype 1b Replicons
            <i>In Vitro</i>

Cheng, Ye; Tsou, Lun K.; Cai, Jianfeng; Aya, Toshihiro; Dutschman, Ginger E.; Gullen, Elizabeth A.; Grill, Susan P.; Chen, Annie Pei Chun; Lindenbach, Brett D.; Hamilton, Andrew D.; Cheng, Yung Chi

doi:10.1128/aac.01206-09

Cited by 25 publications

(27 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hamilton and co-workers recognised the potential of functionalized porphyrin ligands as bona fide receptors for proteinsurface recognition, developing potent ligands for Cyt c. 46,51 These studies are discussed in greater detail later in this article.…”

Section: Porphyrinsmentioning

confidence: 99%

Metal complexes as “protein surface mimetics”

Hewitt

Wilson

2016

Chem. Commun.

View full text Add to dashboard Cite

A key challenge in chemical biology is to identify small molecule regulators for every single protein. However, protein surfaces are notoriously difficult to recognise with synthetic molecules, often having large flat surfaces that are poorly matched to traditional small molecules. In the surface mimetic approach, a supramolecular scaffold is used to project recognition groups in such a manner as to make multivalent non-covalent contacts over a large area of protein surface. Metal based supramolecular scaffolds offer unique advantages over conventional organic molecules for protein binding, inlcuding greater steroechemcial and geometrical diversity conferred through the metal centre and the potential for direct assessment of binding properties and even visualisation in cells without recourse to further functionalisation. This feature article will highlight the current state of the art in protein surface recognition using metal complexes as surface mimetics.

show abstract

Section: Porphyrinsmentioning

confidence: 99%

Metal complexes as “protein surface mimetics”

Hewitt

Wilson

2016

Chem. Commun.

View full text Add to dashboard Cite

show abstract

“…In the case of the members of the Flaviviridae family, antiviral activity of porphyrins, such as some anionic tetraphenylporphyrins, Zinc mesoporphyrins and biliverdin, has been described for a HCV replicon system (Cheng et al . ; Hou et al . ; Zhu et al .…”

Section: Discussionmentioning

confidence: 99%

Inactivation of Dengue and Yellow Fever viruses by heme, cobalt-protoporphyrin IX and tin-protoporphyrin IX

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Many viruses of different families have been inactivated by porphyrins or porphyrin derivatives, including enveloped viruses, such as HIV-1 (3,4), poxvirus (5), hepatitis B virus (6,7), hepatitis C virus (7,8), Marburg, Tacaribe, and Junin viruses (7), bovine herpesvirus (9), and dengue and yellow fever viruses (7,10), as well as nonenveloped viruses, such as poliovirus (9). Porphyrins and their derivatives were also used as enhancers of the effects of other antiviral drugs, as was observed for the combination of heme (or its analogues) with zidovudine for the treatment of HIV-1 infection (11,12), and some porphyrins were conjugated with the neuraminidase inhibitor zanamivir for the treatment of influenza virus infections (13).…”

mentioning

confidence: 99%

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

View full text Add to dashboard Cite

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).

show abstract

A Novel Class of meso -Tetrakis-Porphyrin Derivatives Exhibits Potent Activities against Hepatitis C Virus Genotype 1b Replicons In Vitro

Cited by 25 publications

References 37 publications

Metal complexes as “protein surface mimetics”

Metal complexes as “protein surface mimetics”

Inactivation of Dengue and Yellow Fever viruses by heme, cobalt-protoporphyrin IX and tin-protoporphyrin IX

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

Contact Info

Product

Resources

About