The Phthalocyanine Prototype Derivative Alcian Blue Is the First Synthetic Agent with Selective Anti-Human Immunodeficiency Virus Activity Due to Its gp120 Glycan-Binding Potential

François, Katrien O.; Pannecouque, Christophe; Auwerx, Johan; Lozano, Virginia; Pérez‐Pérez, María‐Jesús; Schols, Dominique; Balzarini, Jan

doi:10.1128/aac.00811-09

Cited by 10 publications

(9 citation statements)

References 41 publications

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“…The results of the cell-based toxicity experiments reveal CC50 values comparable to other studies with values consistently greater than 500 μg/mL [ 11 , 14 ]. The in vitro EC50 values are within a log of previously reported values [ 10 , 11 , 14 ]. Reasons for the variability in efficacy may include differences in product purity and preparation, various HIV or pseudo-virus strains tested, and laboratory equipment calibration.…”

Section: Resultssupporting

confidence: 87%

“…Copper has known bactericidal, fungicidal, and virucidal properties [ 5 – 7 ]. In vitro, copper-based compounds have been shown to prevent HIV infection through several mechanisms: irreversible inactivation of the essential HIV-1 enzyme protease [ 8 ], induction of free radical damage to nucleic acids [ 9 ], prevention of p24 production and syncytia formation in HIV-infected cells [ 9 ], inhibition of gp120 binding [ 10 , 11 ], and prevention of viral fusion [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

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In vitro antiretroviral activity and in vivo toxicity of the potential topical microbicide copper phthalocyanine sulfate

Styczynski

Anwar

Sultana

et al. 2015

Virol J

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BackgroundCopper has antimicrobial properties and has been studied for its activity against viruses, including HIV. Copper complexed within a phthalocyanine ring, forming copper (II) phthalocyanine sulfate (CuPcS), may have a role in microbicide development when used intravaginally.MethodsCuPcS toxicity was tested against cervical epithelial cells, TZM-BL cells, peripheral blood mononuclear cells (PBMC), and cervical explant tissues using cell viability assays. In vivo toxicity was assessed following intravaginal administration of CuPcS in female BALB/C mice and measured using a standardized histology grading system on reproductive tract tissues. Efficacy studies for preventing infection with HIV in the presence of various non-toxic concentrations of CuPcS were carried out in TZM-BL, PBMC, and cervical explant cultures using HIV-1BAL and various pseudovirus subtypes. Non-linear regression was applied to the data to determine the EC50/90 and CC50/90.ResultsCuPcS demonstrated inhibition of HIV infection in PBMCs at concentrations that were non-toxic in cervical epithelial cells and PBMCs with EC50 values of approximately 50 μg/mL. Reproductive tract tissue analysis revealed no toxicity at 100 mg/mL. Human cervical explant tissues challenged with HIV in the presence of CuPcS also revealed a dose–response effect at preventing HIV infection at non-toxic concentrations with an EC50 value of 65 μg/mL.ConclusionThese results suggest that CuPcS may be useful as a topical microbicide in concentrations that can be achieved in the female genital tract.Electronic supplementary materialThe online version of this article (doi:10.1186/s12985-015-0358-5) contains supplementary material, which is available to authorized users.

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Section: Resultssupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

In vitro antiretroviral activity and in vivo toxicity of the potential topical microbicide copper phthalocyanine sulfate

Styczynski

Anwar

Sultana

et al. 2015

Virol J

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“…In particular, the compounds 31h-phthalocyanine (from here simply referred to as phthalocyanine) and hypericin represent the two most appealing molecules. In fact, they show a significantly high affinity for the HR1 region and, additionally, hypericin and different phthalocyanine derivates have been already shown to prevent human immunodeficiency virus (HIV) infections, interfering with the surface glycoprotein gp120 binding and fusion to the host cell (François et al, 2009;Lenard et al, 1993;Vzorov et al, 2003). Furthermore, these two compounds, or their derivatives, also possess different antiviral activities towards other viral species, as it will be discussed below in Section 3.5, and hypericin has also been recently shown to inhibit the infectious bronchitis virus (IBV), an avian coronavirus, acting through a mechanism involving inhibition of the virus-induced cellular apoptosis (Chen et al, 2019b).…”

Section: Virtual Screeningmentioning

confidence: 99%

Targeting the SARS-CoV-2 spike glycoprotein prefusion conformation: virtual screening and molecular dynamics simulations applied to the identification of potential fusion inhibitors

2020

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The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a renewed interest in studying the role of the spike S glycoprotein in regulating coronavirus infections in the natural host. Taking advantage of the cryo-electron microscopy structure of SARS-CoV-2 S trimer in the prefusion conformation, we performed a virtual screening simulation with the aim to identify novel molecules that could be used as fusion inhibitors. The spike glycoprotein structure has been completed using modeling techniques and its inner cavity, needful for the postfusion transition of the trimer, has been scanned for the identification of strongly interacting available drugs. Finally, the stability of the protein-drug top complexes has been tested using classical molecular dynamics simulations. The free energy of interaction of the molecules to the spike protein has been evaluated through the MM/GBSA method and per-residue decomposition analysis. Results have been critically discussed considering previous scientific knowledge concerning the selected compounds and sequence alignments have been carried out to evaluate the spike glycoprotein similarity among the betacoronavirus family members. Finally, a cocktail of drugs that may be used as SARS-CoV-2 fusion inhibitors has been suggested.

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“…293,294 In a number of cases it has been shown that phthalocyanines can have an antiviral activity in the absence of light. 295,296,297,298 Mostly, phthalocyanines have been investigated with respect to the antiviral PDI of blood products. 84,88,288,294,299,300 One silicon phthalocyanine, "Pc4" (36), was specifically developed and investigated for this purpose, as it showed high activities against HIV and VSV, 299,301 and was found to inactivate both cell-free HIV as well as actively replicating HIV and latently infected cells.…”

Section: Phthalocyaninesmentioning

confidence: 99%

Trends and targets in antiviral phototherapy

Wiehe

O’Brien

Senge

2019

Photochem Photobiol Sci

232

168

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The Phthalocyanine Prototype Derivative Alcian Blue Is the First Synthetic Agent with Selective Anti-Human Immunodeficiency Virus Activity Due to Its gp120 Glycan-Binding Potential

Cited by 10 publications

References 41 publications

In vitro antiretroviral activity and in vivo toxicity of the potential topical microbicide copper phthalocyanine sulfate

In vitro antiretroviral activity and in vivo toxicity of the potential topical microbicide copper phthalocyanine sulfate

Targeting the SARS-CoV-2 spike glycoprotein prefusion conformation: virtual screening and molecular dynamics simulations applied to the identification of potential fusion inhibitors

Trends and targets in antiviral phototherapy

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