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  1. Article ; Online: Chemical Constituents of Cassia abbreviata and Their Anti-HIV-1 Activity

    Xianwen Yang / Zhihui He / Yue Zheng / Ning Wang / Martin Mulinge / Jean-Claude Schmit / André Steinmetz / Carole Seguin-Devaux

    Molecules, Vol 26, Iss 2455, p

    2021  Volume 2455

    Abstract: Three new ( 1 – 3 ) and 25 known compounds were isolated from the crude extract of Cassia abbreviata . The chemical structures of new compounds were established by extensive spectroscopic analyses including 1D and 2D NMR and HRESIMS. Cassiabrevone ( 1 ) ... ...

    Abstract Three new ( 1 – 3 ) and 25 known compounds were isolated from the crude extract of Cassia abbreviata . The chemical structures of new compounds were established by extensive spectroscopic analyses including 1D and 2D NMR and HRESIMS. Cassiabrevone ( 1 ) is the first heterodimer of guibourtinidol and planchol A. Compound 2 was a new chalcane, while 3 was a new naphthalene. Cassiabrevone ( 1 ), guibourtinidol-(4α→8)-epiafzelechin ( 4 ), taxifolin ( 8 ), oleanolic acid ( 17 ), piceatannol ( 22 ), and palmitic acid ( 28 ), exhibited potent anti-HIV-1 activity with IC 50 values of 11.89 µM, 15.39 µM, 49.04 µM, 7.95 µM, 3.58 µM, and 15.97 µM, respectively.
    Keywords Cassia abbreviata ; Fabaceae ; anti-HIV ; heterodimer ; flavonoid ; Organic chemistry ; QD241-441
    Language English
    Publishing date 2021-04-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Active Components from Cassia abbreviata Prevent HIV-1 Entry by Distinct Mechanisms of Action

    Yue Zheng / Xian-Wen Yang / Dominique Schols / Mattia Mori / Bruno Botta / Andy Chevigné / Martin Mulinge / André Steinmetz / Jean-Claude Schmit / Carole Seguin-Devaux

    International Journal of Molecular Sciences, Vol 22, Iss 5052, p

    2021  Volume 5052

    Abstract: Cassia abbreviata is widely used in Sub-Saharan Africa for treating many diseases, including HIV-1 infection. We have recently described the chemical structures of 28 compounds isolated from an alcoholic crude extract of barks and roots of C. abbreviata , ...

    Abstract Cassia abbreviata is widely used in Sub-Saharan Africa for treating many diseases, including HIV-1 infection. We have recently described the chemical structures of 28 compounds isolated from an alcoholic crude extract of barks and roots of C. abbreviata , and showed that six bioactive compounds inhibit HIV-1 infection. In the present study, we demonstrate that the six compounds block HIV-1 entry into cells: oleanolic acid, palmitic acid, taxifolin, piceatannol, guibourtinidol-(4α→8)-epiafzelechin, and a novel compound named as cassiabrevone. We report, for the first time, that guibourtinidol-(4α→8)-epiafzelechin and cassiabrevone inhibit HIV-1 entry (IC 50 of 42.47 µM and 30.96 µM, respectively), as well as that piceatannol interacts with cellular membranes. Piceatannol inhibits HIV-1 infection in a dual-chamber assay mimicking the female genital tract, as well as HSV infection, emphasizing its potential as a microbicide. Structure-activity relationships (SAR) showed that pharmacophoric groups of piceatannol are strictly required to inhibit HIV-1 entry. By a ligand-based in silico study, we speculated that piceatannol and norartocarpetin may have a very similar mechanism of action and efficacy because of the highly comparable pharmacophoric and 3D space, while guibourtinidol-(4α→8)-epiafzelechin and cassiabrevone may display a different mechanism. We finally show that cassiabrevone plays a major role of the crude extract of CA by blocking the binding activity of HIV-1 gp120 and CD4.
    Keywords natural products ; Cassia abbreviata ; HIV-1 entry ; piceatannol ; structure-activity relationship ; pharmacophoric studies ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 540
    Language English
    Publishing date 2021-05-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: The Envelope Cytoplasmic Tail of HIV-1 Subtype C Contributes to Poor Replication Capacity through Low Viral Infectivity and Cell-to-Cell Transmission.

    Eveline Santos da Silva / Martin Mulinge / Morgane Lemaire / Cécile Masquelier / Cyprien Beraud / Arkadiusz Rybicki / Jean-Yves Servais / Gilles Iserentant / Jean-Claude Schmit / Carole Seguin-Devaux / Danielle Perez Bercoff

    PLoS ONE, Vol 11, Iss 9, p e

    2016  Volume 0161596

    Abstract: The cytoplasmic tail (gp41CT) of the HIV-1 envelope (Env) mediates Env incorporation into virions and regulates Env intracellular trafficking. Little is known about the functional impact of variability in this domain. To address this issue, we compared ... ...

    Abstract The cytoplasmic tail (gp41CT) of the HIV-1 envelope (Env) mediates Env incorporation into virions and regulates Env intracellular trafficking. Little is known about the functional impact of variability in this domain. To address this issue, we compared the replication of recombinant virus pairs carrying the full Env (Env viruses) or the Env ectodomain fused to the gp41CT of NL4.3 (EnvEC viruses) (12 subtype C and 10 subtype B pairs) in primary CD4+ T-cells and monocyte-derived-macrophages (MDMs). In CD4+ T-cells, replication was as follows: B-EnvEC = B-Env>C-EnvEC>C-Env, indicating that the gp41CT of subtype C contributes to the low replicative capacity of this subtype. In MDMs, in contrast, replication capacity was comparable for all viruses regardless of subtype and of gp41CT. In CD4+ T-cells, viral entry, viral release and viral gene expression were similar. However, infectivity of free virions and cell-to-cell transmission of C-Env viruses released by CD4+ T-cells was lower, suggestive of lower Env incorporation into virions. Subtype C matrix only minimally rescued viral replication and failed to restore infectivity of free viruses and cell-to-cell transmission. Taken together, these results show that polymorphisms in the gp41CT contribute to viral replication capacity and suggest that the number of Env spikes per virion may vary across subtypes. These findings should be taken into consideration in the design of vaccines.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: The Envelope Cytoplasmic Tail of HIV-1 Subtype C Contributes to Poor Replication Capacity through Low Viral Infectivity and Cell-to-Cell Transmission.

    Eveline Santos da Silva / Martin Mulinge / Morgane Lemaire / Cécile Masquelier / Cyprien Beraud / Arkadiusz Rybicki / Jean-Yves Servais / Gilles Iserentant / Jean-Claude Schmit / Carole Seguin-Devaux / Danielle Perez Bercoff

    PLoS ONE, Vol 11, Iss 9, p e

    2016  Volume 0161596

    Abstract: The cytoplasmic tail (gp41CT) of the HIV-1 envelope (Env) mediates Env incorporation into virions and regulates Env intracellular trafficking. Little is known about the functional impact of variability in this domain. To address this issue, we compared ... ...

    Abstract The cytoplasmic tail (gp41CT) of the HIV-1 envelope (Env) mediates Env incorporation into virions and regulates Env intracellular trafficking. Little is known about the functional impact of variability in this domain. To address this issue, we compared the replication of recombinant virus pairs carrying the full Env (Env viruses) or the Env ectodomain fused to the gp41CT of NL4.3 (EnvEC viruses) (12 subtype C and 10 subtype B pairs) in primary CD4+ T-cells and monocyte-derived-macrophages (MDMs). In CD4+ T-cells, replication was as follows: B-EnvEC = B-Env>C-EnvEC>C-Env, indicating that the gp41CT of subtype C contributes to the low replicative capacity of this subtype. In MDMs, in contrast, replication capacity was comparable for all viruses regardless of subtype and of gp41CT. In CD4+ T-cells, viral entry, viral release and viral gene expression were similar. However, infectivity of free virions and cell-to-cell transmission of C-Env viruses released by CD4+ T-cells was lower, suggestive of lower Env incorporation into virions. Subtype C matrix only minimally rescued viral replication and failed to restore infectivity of free viruses and cell-to-cell transmission. Taken together, these results show that polymorphisms in the gp41CT contribute to viral replication capacity and suggest that the number of Env spikes per virion may vary across subtypes. These findings should be taken into consideration in the design of vaccines.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2016-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Correction

    Martin Mulinge / Morgane Lemaire / Jean-Yves Servais / Arkadiusz Rybicki / Daniel Struck / Eveline Santos da Silva / Chris Verhofstede / Yolanda Lie / Carole Seguin-Devaux / Jean-Claude Schmit / Danielle Perez Bercoff

    PLoS ONE, Vol 8, Iss

    HIV-1 Tropism Determination Using a Phenotypic Env Recombinant Viral Assay Highlights Overestimation of CXCR4-Usage by Genotypic Prediction Algorithms for CRRF01_AE and CRF02_AG

    2013  Volume 7

    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2013-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Correction

    Martin Mulinge / Morgane Lemaire / Jean-Yves Servais / Arkadiusz Rybicki / Daniel Struck / Eveline Santos da Silva / Chris Verhofstede / Yolanda Lie / Carole Seguin-Devaux / Jean-Claude Schmit / Danielle Perez Bercoff

    PLoS ONE, Vol 8, Iss

    HIV-1 Tropism Determination Using a Phenotypic Env Recombinant Viral Assay Highlights Overestimation of CXCR4-Usage by Genotypic Prediction Algorithms for CRRF01_AE and CRF02_AG.

    2013  Volume 7

    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2013-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: HIV-1 tropism determination using a phenotypic Env recombinant viral assay highlights overestimation of CXCR4-usage by genotypic prediction algorithms for CRF01_AE and CRF02_AG [corrected].

    Martin Mulinge / Morgane Lemaire / Jean-Yves Servais / Arkadiusz Rybicki / Daniel Struck / Eveline Santos da Silva / Chris Verhofstede / Yolanda Lie / Carole Seguin-Devaux / Jean-Claude Schmit / Danielle Perez Bercoff

    PLoS ONE, Vol 8, Iss 5, p e

    2013  Volume 60566

    Abstract: Background Human Immunodeficiency virus type-1 (HIV) entry into target cells involves binding of the viral envelope (Env) to CD4 and a coreceptor, mainly CCR5 or CXCR4. The only currently licensed HIV entry inhibitor, maraviroc, targets CCR5, and the ... ...

    Abstract Background Human Immunodeficiency virus type-1 (HIV) entry into target cells involves binding of the viral envelope (Env) to CD4 and a coreceptor, mainly CCR5 or CXCR4. The only currently licensed HIV entry inhibitor, maraviroc, targets CCR5, and the presence of CXCX4-using strains must be excluded prior to treatment. Co-receptor usage can be assessed by phenotypic assays or through genotypic prediction. Here we compared the performance of a phenotypic Env-Recombinant Viral Assay (RVA) to the two most widely used genotypic prediction algorithms, Geno2Pheno[coreceptor] and webPSSM. Methods Co-receptor tropism of samples from 73 subtype B and 219 non-B infections was measured phenotypically using a luciferase-tagged, NL4-3-based, RVA targeting Env. In parallel, tropism was inferred genotypically from the corresponding V3-loop sequences using Geno2Pheno[coreceptor] (5-20% FPR) and webPSSM-R5X4. For discordant samples, phenotypic outcome was retested using co-receptor antagonists or the validated Trofile® Enhanced-Sensitivity-Tropism-Assay. Results The lower detection limit of the RVA was 2.5% and 5% for X4 and R5 minority variants respectively. A phenotype/genotype result was obtained for 210 samples. Overall, concordance of phenotypic results with Geno2Pheno[coreceptor] was 85.2% and concordance with webPSSM was 79.5%. For subtype B, concordance with Geno2pheno[coreceptor] was 94.4% and concordance with webPSSM was 79.6%. High concordance of genotypic tools with phenotypic outcome was seen for subtype C (90% for both tools). Main discordances involved CRF01_AE and CRF02_AG for both algorithms (CRF01_AE: 35.9% discordances with Geno2Pheno[coreceptor] and 28.2% with webPSSM; CRF02_AG: 20.7% for both algorithms). Genotypic prediction overestimated CXCR4-usage for both CRFs. For webPSSM, 40% discordance was observed for subtype A. Conclusions Phenotypic assays remain the most accurate for most non-B subtypes and new subtype-specific rules should be developed for non-B subtypes, as research studies more and more draw ...
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2013-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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