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Article ; Online: Increased CMV IgG Antibody Titer is Associated with Non-AIDS Events among Virologically Suppressed HIV-Positive Persons.

Hodowanec, Aimee C / Lurain, Nell S / Krishnan, Supriya / Bosch, Ronald J / Landay, Alan L

Pathogens & immunity

2019 Volume 4, Issue 1, Page(s) 66–78

Abstract: Background: Among HIV-positive individuals, increased levels of inflammation and immune activation persist even in the setting of effective antiretroviral therapy (ART) and are associated with greater rates of non-AIDS events. The etiology of this ... ...

Abstract	Background: Among HIV-positive individuals, increased levels of inflammation and immune activation persist even in the setting of effective antiretroviral therapy (ART) and are associated with greater rates of non-AIDS events. The etiology of this persistent inflammation is incompletely understood. Methods: Using a well-characterized cohort of 322 HIV-infected individuals on suppressive ART, we conducted a case-control study. Cytomegalovirus (CMV) immunoglobulin G (IgG) levels, plasma biomarkers, and T-cell phenotypes were measured/characterized from samples collected 1 year after ART initiation. Conditional logistic regression for matched case-control studies analyzed the associations of year 1 CMV-specific IgG level with the subsequent occurrence of any non-AIDS event. Correlations between continuous CMV IgG antibody levels and soluble and cellular markers were assessed. Results: We found that higher levels of CMV IgG were associated with increased risk of non-AIDS events (OR = 1.58 per IQR [95% CI: 1.12, 2.24], Conclusions: The magnitude of the host immune response to CMV may play a role in the persistent inflammation and resultant morbid events observed in the HIV-positive population.
Language	English
Publishing date	2019-02-14
Publishing country	United States
Document type	Journal Article
ISSN	2469-2964
ISSN (online)	2469-2964
DOI	10.20411/pai.v4i1.255
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Author Correction: Ginkgolic acid inhibits fusion of enveloped viruses.

Borenstein, Ronen / Hanson, Barbara A / Markosyan, Ruben M / Gallo, Elisa S / Narasipura, Srinivas D / Bhutta, Maimoona / Shechter, Oren / Lurain, Nell S / Cohen, Fredric S / Al-Harthi, Lena / Nicholson, Daniel A

Scientific reports

2020 Volume 10, Issue 1, Page(s) 7499

Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

Abstract	An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Language	English
Publishing date	2020-05-05
Publishing country	England
Document type	Published Erratum
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-64445-y
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Article ; Online: Antiviral drug resistance of human cytomegalovirus.

Lurain, Nell S / Chou, Sunwen

Clinical microbiology reviews

2010 Volume 23, Issue 4, Page(s) 689–712

Abstract: The study of human cytomegalovirus (HCMV) antiviral drug resistance has enhanced knowledge of the virological targets and the mechanisms of antiviral activity. The currently approved drugs, ganciclovir (GCV), foscarnet (FOS), and cidofovir (CDV), target ... ...

Abstract	The study of human cytomegalovirus (HCMV) antiviral drug resistance has enhanced knowledge of the virological targets and the mechanisms of antiviral activity. The currently approved drugs, ganciclovir (GCV), foscarnet (FOS), and cidofovir (CDV), target the viral DNA polymerase. GCV anabolism also requires phosphorylation by the virus-encoded UL97 kinase. GCV resistance mutations have been identified in both genes, while FOS and CDV mutations occur only in the DNA polymerase gene. Confirmation of resistance mutations requires phenotypic analysis; however, phenotypic assays are too time-consuming for diagnostic purposes. Genotypic assays based on sequencing provide more rapid results but are dependent on prior validation by phenotypic methods. Reports from many laboratories have produced an evolving list of confirmed resistance mutations, although differences in interpretation have led to some confusion. Recombinant phenotyping methods performed in a few research laboratories have resolved some of the conflicting results. Treatment options for drug-resistant HCMV infections are complex and have not been subjected to controlled clinical trials, although consensus guidelines have been proposed. This review summarizes the virological and clinical data pertaining to HCMV antiviral drug resistance.
MeSH term(s)	Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Cidofovir ; Cytomegalovirus/drug effects ; Cytomegalovirus/genetics ; Cytomegalovirus Infections/drug therapy ; Cytosine/analogs & derivatives ; Cytosine/pharmacology ; Cytosine/therapeutic use ; DNA-Directed DNA Polymerase ; Drug Resistance, Viral/genetics ; Foscarnet/pharmacology ; Foscarnet/therapeutic use ; Ganciclovir/pharmacology ; Ganciclovir/therapeutic use ; Genome, Viral ; Humans ; Organophosphonates/pharmacology ; Organophosphonates/therapeutic use ; Phosphotransferases (Alcohol Group Acceptor)/genetics ; Phosphotransferases (Alcohol Group Acceptor)/metabolism ; Sequence Analysis, DNA
Chemical Substances	Antiviral Agents ; Organophosphonates ; Foscarnet (364P9RVW4X) ; Cytosine (8J337D1HZY) ; Phosphotransferases (Alcohol Group Acceptor) (EC 2.7.1.-) ; ganciclovir kinase (EC 2.7.1.-) ; DNA-Directed DNA Polymerase (EC 2.7.7.7) ; Cidofovir (JIL713Q00N) ; Ganciclovir (P9G3CKZ4P5)
Language	English
Publishing date	2010-10-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	645015-5
ISSN	1098-6618 ; 0893-8512
ISSN (online)	1098-6618
ISSN	0893-8512
DOI	10.1128/CMR.00009-10
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Article ; Online: Author Correction

Ronen Borenstein / Barbara A. Hanson / Ruben M. Markosyan / Elisa S. Gallo / Srinivas D. Narasipura / Maimoona Bhutta / Oren Shechter / Nell S. Lurain / Fredric S. Cohen / Lena Al-Harthi / Daniel A. Nicholson

Scientific Reports, Vol 10, Iss 1, Pp 1-

Ginkgolic acid inhibits fusion of enveloped viruses

2020 Volume 1

Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

Abstract	An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2020-05-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Ginkgolic acid inhibits fusion of enveloped viruses.

Scientific reports

2020 Volume 10, Issue 1, Page(s) 4746

Abstract: Ginkgolic acids (GA) are alkylphenol constituents of the leaves and fruits of Ginkgo biloba. GA has shown pleiotropic effects in vitro, including: antitumor effects through inhibition of lipogenesis; decreased expression of invasion associated proteins ... ...

Abstract	Ginkgolic acids (GA) are alkylphenol constituents of the leaves and fruits of Ginkgo biloba. GA has shown pleiotropic effects in vitro, including: antitumor effects through inhibition of lipogenesis; decreased expression of invasion associated proteins through AMPK activation; and potential rescue of amyloid-β (Aβ) induced synaptic impairment. GA was also reported to have activity against Escherichia coli and Staphylococcus aureus. Several mechanisms for this activity have been suggested including: SUMOylation inhibition; blocking formation of the E1-SUMO intermediate; inhibition of fatty acid synthase; non-specific SIRT inhibition; and activation of protein phosphatase type-2C. Here we report that GA inhibits Herpes simplex virus type 1 (HSV-1) by inhibition of both fusion and viral protein synthesis. Additionally, we report that GA inhibits human cytomegalovirus (HCMV) genome replication and Zika virus (ZIKV) infection of normal human astrocytes (NHA). We show a broad spectrum of fusion inhibition by GA of all three classes of fusion proteins including HIV, Ebola virus (EBOV), influenza A virus (IAV) and Epstein Barr virus (EBV). In addition, we show inhibition of a non-enveloped adenovirus. Our experiments suggest that GA inhibits virion entry by blocking the initial fusion event. Data showing inhibition of HSV-1 and CMV replication, when GA is administered post-infection, suggest a possible secondary mechanism targeting protein and DNA synthesis. Thus, in light of the strong effect of GA on viral infection, even after the infection begins, it may potentially be used to treat acute infections (e.g. Coronavirus, EBOV, ZIKV, IAV and measles), and also topically for the successful treatment of active lesions (e.g. HSV-1, HSV-2 and varicella-zoster virus (VZV)).
MeSH term(s)	Animals ; Antiviral Agents/pharmacology ; Astrocytes/metabolism ; Chlorocebus aethiops ; DNA Replication/drug effects ; DNA Virus Infections/metabolism ; DNA Virus Infections/virology ; DNA Viruses/drug effects ; DNA Viruses/genetics ; DNA, Viral/genetics ; HEK293 Cells ; Humans ; RNA Virus Infections/metabolism ; RNA Virus Infections/virology ; RNA Viruses/drug effects ; RNA Viruses/genetics ; Salicylates/pharmacology ; Vero Cells ; Viral Envelope Proteins/antagonists & inhibitors ; Viral Envelope Proteins/biosynthesis ; Viral Fusion Proteins/antagonists & inhibitors ; Viral Fusion Proteins/biosynthesis ; Virion/drug effects ; Virus Internalization/drug effects ; Virus Replication/drug effects
Chemical Substances	Antiviral Agents ; DNA, Viral ; Salicylates ; Viral Envelope Proteins ; Viral Fusion Proteins ; ginkgolic acid (22910-60-7)
Keywords	covid19
Language	English
Publishing date	2020-03-16
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-61700-0
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Article ; Online: Convallatoxin-Induced Reduction of Methionine Import Effectively Inhibits Human Cytomegalovirus Infection and Replication.

Cohen, Tobias / Williams, John D / Opperman, Timothy J / Sanchez, Roberto / Lurain, Nell S / Tortorella, Domenico

Journal of virology

2016 Volume 90, Issue 23, Page(s) 10715–10727

Abstract: Cytomegalovirus (CMV) is a ubiquitous human pathogen that increases the morbidity and mortality of immunocompromised individuals. The current FDA-approved treatments for CMV infection are intended to be virus specific, yet they have significant adverse ... ...

Abstract	Cytomegalovirus (CMV) is a ubiquitous human pathogen that increases the morbidity and mortality of immunocompromised individuals. The current FDA-approved treatments for CMV infection are intended to be virus specific, yet they have significant adverse side effects, including nephrotoxicity and hematological toxicity. Thus, there is a medical need for safer and more effective CMV therapeutics. Using a high-content screen, we identified the cardiac glycoside convallatoxin as an effective compound that inhibits CMV infection. Using a panel of cardiac glycoside variants, we assessed the structural elements critical for anti-CMV activity by both experimental and in silico methods. Analysis of the antiviral effects, toxicities, and pharmacodynamics of different variants of cardiac glycosides identified the mechanism of inhibition as reduction of methionine import, leading to decreased immediate-early gene translation without significant toxicity. Also, convallatoxin was found to dramatically reduce the proliferation of clinical CMV strains, implying that its mechanism of action is an effective strategy to block CMV dissemination. Our study has uncovered the mechanism and structural elements of convallatoxin, which are important for effectively inhibiting CMV infection by targeting the expression of immediate-early genes. Importance: Cytomegalovirus is a highly prevalent virus capable of causing severe disease in certain populations. The current FDA-approved therapeutics all target the same stage of the viral life cycle and induce toxicity and viral resistance. We identified convallatoxin, a novel cell-targeting antiviral that inhibits CMV infection by decreasing the synthesis of viral proteins. At doses low enough for cells to tolerate, convallatoxin was able to inhibit primary isolates of CMV, including those resistant to the anti-CMV drug ganciclovir. In addition to identifying convallatoxin as a novel antiviral, limiting mRNA translation has a dramatic impact on CMV infection and proliferation.
MeSH term(s)	Antiviral Agents/chemistry ; Antiviral Agents/pharmacology ; Biological Transport, Active/drug effects ; Cardiac Glycosides/chemistry ; Cardiac Glycosides/pharmacology ; Cell Line ; Cytomegalovirus/drug effects ; Cytomegalovirus/genetics ; Cytomegalovirus/physiology ; Cytomegalovirus Infections/metabolism ; Cytomegalovirus Infections/prevention & control ; Cytomegalovirus Infections/virology ; Genes, Immediate-Early/drug effects ; Genes, Viral/drug effects ; Humans ; Methionine/metabolism ; Microbial Sensitivity Tests ; Models, Molecular ; Molecular Structure ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; RNA, Viral/genetics ; RNA, Viral/metabolism ; Strophanthins/chemistry ; Strophanthins/pharmacology ; Structure-Activity Relationship ; Virus Replication/drug effects
Chemical Substances	Antiviral Agents ; Cardiac Glycosides ; RNA, Messenger ; RNA, Viral ; Strophanthins ; Methionine (AE28F7PNPL) ; convallatoxin (JY264VIR1Y)
Keywords	covid19
Language	English
Publishing date	2016-11-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.01050-16
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Article ; Online: Ginkgolic acid inhibits fusion of enveloped viruses

Scientific Reports, Vol 10, Iss 1, Pp 1-

2020 Volume 12

Abstract: Abstract Ginkgolic acids (GA) are alkylphenol constituents of the leaves and fruits of Ginkgo biloba. GA has shown pleiotropic effects in vitro, including: antitumor effects through inhibition of lipogenesis; decreased expression of invasion associated ... ...

Abstract	Abstract Ginkgolic acids (GA) are alkylphenol constituents of the leaves and fruits of Ginkgo biloba. GA has shown pleiotropic effects in vitro, including: antitumor effects through inhibition of lipogenesis; decreased expression of invasion associated proteins through AMPK activation; and potential rescue of amyloid-β (Aβ) induced synaptic impairment. GA was also reported to have activity against Escherichia coli and Staphylococcus aureus. Several mechanisms for this activity have been suggested including: SUMOylation inhibition; blocking formation of the E1-SUMO intermediate; inhibition of fatty acid synthase; non-specific SIRT inhibition; and activation of protein phosphatase type-2C. Here we report that GA inhibits Herpes simplex virus type 1 (HSV-1) by inhibition of both fusion and viral protein synthesis. Additionally, we report that GA inhibits human cytomegalovirus (HCMV) genome replication and Zika virus (ZIKV) infection of normal human astrocytes (NHA). We show a broad spectrum of fusion inhibition by GA of all three classes of fusion proteins including HIV, Ebola virus (EBOV), influenza A virus (IAV) and Epstein Barr virus (EBV). In addition, we show inhibition of a non-enveloped adenovirus. Our experiments suggest that GA inhibits virion entry by blocking the initial fusion event. Data showing inhibition of HSV-1 and CMV replication, when GA is administered post-infection, suggest a possible secondary mechanism targeting protein and DNA synthesis. Thus, in light of the strong effect of GA on viral infection, even after the infection begins, it may potentially be used to treat acute infections (e.g. Coronavirus, EBOV, ZIKV, IAV and measles), and also topically for the successful treatment of active lesions (e.g. HSV-1, HSV-2 and varicella-zoster virus (VZV)).
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2020-03-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Association of Human Cytomegalovirus with Biomarkers of Inflammation and Immune Activation in HIV-1-Infected Women.

Lurain, Nell S / Hanson, Barbara A / Hotton, Anna L / Weber, Kathleen M / Cohen, Mardge H / Landay, Alan L

AIDS research and human retroviruses

2016 Volume 32, Issue 2, Page(s) 134–143

Abstract: Three groups of cytomegalovirus (CMV)-seropositive women (total n = 164) were selected from the Chicago Women's Interagency HIV-1 Study to investigate the association between CMV coinfection and immune activation: (1) HIV-1 viremic, (2) HIV-1 aviremic, ... ...

Abstract	Three groups of cytomegalovirus (CMV)-seropositive women (total n = 164) were selected from the Chicago Women's Interagency HIV-1 Study to investigate the association between CMV coinfection and immune activation: (1) HIV-1 viremic, (2) HIV-1 aviremic, and (3) HIV-1 uninfected. Quantitative measures of CMV serum IgG, CMV DNA, and serum biomarkers interleukin (IL)-6, soluble CD163 (sCD163), soluble CD14 (sCD14), and interferon gamma-induced protein (IP10) were obtained. Levels of CMV IgG and the serum biomarkers were significantly higher in the HIV-1 viremic group compared to the aviremic and uninfected groups (p < 0.001). No significant associations with CMV IgG levels were found for HIV-uninfected women. When each of the HIV-infected groups was analyzed, sCD14 levels in the viremic women were significantly associated with CMV IgG levels with p < 0.02 when adjusted for age, CD4 count, and HIV viral load. There was also a modest association (p = 0.036) with IL-6 from plasma and cervical vaginal lavage specimens both unadjusted and adjusted for CD4 count and HIV viral load. The association of CMV IgG level with sCD14 implicates the monocyte as a potential site for interaction of the two viruses, which eventually may lead to non-AIDS-defining pathological conditions.
MeSH term(s)	Adult ; Anti-HIV Agents/therapeutic use ; Antibodies, Viral/blood ; Antigens, CD/blood ; Antigens, Differentiation, Myelomonocytic/blood ; Biomarkers/blood ; Coinfection/blood ; Coinfection/immunology ; Coinfection/virology ; Cytomegalovirus/immunology ; Cytomegalovirus Infections/drug therapy ; Cytomegalovirus Infections/immunology ; Cytomegalovirus Infections/virology ; Female ; HIV Infections/drug therapy ; HIV Infections/immunology ; HIV Infections/virology ; HIV-1/immunology ; Humans ; Immunoglobulin G/blood ; Inflammation/immunology ; Inflammation/virology ; Interferon-gamma/blood ; Interleukin-6/blood ; Lipopolysaccharide Receptors/blood ; Middle Aged ; Raltegravir Potassium/therapeutic use ; Receptors, Cell Surface/blood ; Viral Load ; Viremia/virology
Chemical Substances	Anti-HIV Agents ; Antibodies, Viral ; Antigens, CD ; Antigens, Differentiation, Myelomonocytic ; Biomarkers ; CD163 antigen ; IL6 protein, human ; Immunoglobulin G ; Interleukin-6 ; Lipopolysaccharide Receptors ; Receptors, Cell Surface ; Raltegravir Potassium (43Y000U234) ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2016-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	639130-8
ISSN	1931-8405 ; 0889-2229
ISSN (online)	1931-8405
ISSN	0889-2229
DOI	10.1089/AID.2015.0169
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Ginkgolic acid inhibits fusion of enveloped viruses

Sci Rep

Abstract	Ginkgolic acids (GA) are alkylphenol constituents of the leaves and fruits of Ginkgo biloba. GA has shown pleiotropic effects in vitro, including: antitumor effects through inhibition of lipogenesis; decreased expression of invasion associated proteins through AMPK activation; and potential rescue of amyloid-ß (Aß) induced synaptic impairment. GA was also reported to have activity against Escherichia coli and Staphylococcus aureus. Several mechanisms for this activity have been suggested including: SUMOylation inhibition; blocking formation of the E1-SUMO intermediate; inhibition of fatty acid synthase; non-specific SIRT inhibition; and activation of protein phosphatase type-2C. Here we report that GA inhibits Herpes simplex virus type 1 (HSV-1) by inhibition of both fusion and viral protein synthesis. Additionally, we report that GA inhibits human cytomegalovirus (HCMV) genome replication and Zika virus (ZIKV) infection of normal human astrocytes (NHA). We show a broad spectrum of fusion inhibition by GA of all three classes of fusion proteins including HIV, Ebola virus (EBOV), influenza A virus (IAV) and Epstein Barr virus (EBV). In addition, we show inhibition of a non-enveloped adenovirus. Our experiments suggest that GA inhibits virion entry by blocking the initial fusion event. Data showing inhibition of HSV-1 and CMV replication, when GA is administered post-infection, suggest a possible secondary mechanism targeting protein and DNA synthesis. Thus, in light of the strong effect of GA on viral infection, even after the infection begins, it may potentially be used to treat acute infections (e.g. Coronavirus, EBOV, ZIKV, IAV and measles), and also topically for the successful treatment of active lesions (e.g. HSV-1, HSV-2 and varicella-zoster virus (VZV)).
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #740043
Database	COVID19

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Article ; Online: Ginkgolic acid inhibits fusion of enveloped viruses

Borenstein, Ronen / Hanson, Barbara A. / Markosyan, Ruben M. / Gallo, Elisa S. / Narasipura, Srinivas D. / Bhutta, Maimoona / Shechter, Oren / Lurain, Nell S. / Cohen, Fredric S. / Al-Harthi, Lena / Nicholson, Daniel A.

reponame:Expeditio Repositorio Institucional UJTL ; instname:Universidad de Bogotá Jorge Tadeo Lozano

2020

Abstract: Ginkgolic acids (GA) are alkylphenol constituents of the leaves and fruits of Ginkgo biloba. GA has shown pleiotropic efects in vitro, including: antitumor efects through inhibition of lipogenesis; decreased expression of invasion associated proteins ... ...

Abstract	Ginkgolic acids (GA) are alkylphenol constituents of the leaves and fruits of Ginkgo biloba. GA has shown pleiotropic efects in vitro, including: antitumor efects through inhibition of lipogenesis; decreased expression of invasion associated proteins through AMPK activation; and potential rescue of amyloid-β (Aβ) induced synaptic impairment. GA was also reported to have activity against Escherichia coli and Staphylococcus aureus. Several mechanisms for this activity have been suggested including: SUMOylation inhibition; blocking formation of the E1-SUMO intermediate; inhibition of fatty acid synthase; non-specifc SIRT inhibition; and activation of protein phosphatase type-2C. Here we report that GA inhibits Herpes simplex virus type 1 (HSV-1) by inhibition of both fusion and viral protein synthesis. Additionally, we report that GA inhibits human cytomegalovirus (HCMV) genome replication and Zika virus (ZIKV) infection of normal human astrocytes (NHA). We show a broad spectrum of fusion inhibition by GA of all three classes of fusion proteins including HIV, Ebola virus (EBOV), infuenza A virus (IAV) and Epstein Barr virus (EBV). In addition, we show inhibition of a non-enveloped adenovirus. Our experiments suggest that GA inhibits virion entry by blocking the initial fusion event. Data showing inhibition of HSV-1 and CMV replication, when GA is administered post-infection, suggest a possible secondary mechanism targeting protein and DNA synthesis. Thus, in light of the strong efect of GA on viral infection, even after the infection begins, it may potentially be used to treat acute infections (e.g. Coronavirus, EBOV, ZIKV, IAV and measles), and also topically for the successful treatment of active lesions (e.g. HSV-1, HSV-2 and varicella-zoster virus (VZV)).
Keywords	COVID-19 ; Enveloped viruses ; Ginkgolic acid inhibits ; Síndrome respiratorio agudo grave ; SARS-CoV-2 ; Coronavirus ; covid19
Publisher	Science Direct
Publishing country	co
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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