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Article ; Online: Antiviral Activity of Probenecid and Oseltamivir on Influenza Virus Replication.

Murray, Jackelyn / Martin, David E / Sancilio, Fred D / Tripp, Ralph A

2023 Volume 15, Issue 12

Abstract: Influenza can cause respiratory infections, leading to significant morbidity and mortality in humans. While current influenza vaccines offer varying levels of protection, there remains a pressing need for effective antiviral drugs to supplement vaccine ... ...

Abstract	Influenza can cause respiratory infections, leading to significant morbidity and mortality in humans. While current influenza vaccines offer varying levels of protection, there remains a pressing need for effective antiviral drugs to supplement vaccine efforts. Currently, the FDA-approved antiviral drugs for influenza include oseltamivir, zanamivir, peramivir, and baloxavir marboxil. These antivirals primarily target the virus, making them vulnerable to drug resistance. In this study, we evaluated the efficacy of the neuraminidase inhibitor, oseltamivir, against probenecid, which targets the host cells and is less likely to engender resistance. Our results show that probenecid has superior antiviral efficacy compared to oseltamivir in both in vitro replication assays and in vivo mouse models of influenza infection.
MeSH term(s)	Humans ; Animals ; Mice ; Oseltamivir/pharmacology ; Oseltamivir/therapeutic use ; Influenza, Human ; Probenecid/pharmacology ; Probenecid/therapeutic use ; Influenza Vaccines/therapeutic use ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Enzyme Inhibitors/pharmacology ; Virus Replication ; Neuraminidase ; Drug Resistance, Viral
Chemical Substances	Oseltamivir (20O93L6F9H) ; Probenecid (PO572Z7917) ; Influenza Vaccines ; Antiviral Agents ; Enzyme Inhibitors ; Neuraminidase (EC 3.2.1.18)
Language	English
Publishing date	2023-11-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v15122366
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Probenecid Inhibits Influenza A(H5N1) and A(H7N9) Viruses In Vitro and in Mice.

Murray, Jackelyn / Martin, David E / Hosking, Sarah / Orr-Burks, Nichole / Hogan, Robert J / Tripp, Ralph A

Viruses

2024 Volume 16, Issue 1

Abstract: Avian influenza (AI) viruses cause infection in birds and humans. Several H5N1 and H7N9 variants are highly pathogenic avian influenza (HPAI) viruses. H5N1 is a highly infectious bird virus infecting primarily poultry, but unlike other AIs, H5N1 also ... ...

Abstract	Avian influenza (AI) viruses cause infection in birds and humans. Several H5N1 and H7N9 variants are highly pathogenic avian influenza (HPAI) viruses. H5N1 is a highly infectious bird virus infecting primarily poultry, but unlike other AIs, H5N1 also infects mammals and transmits to humans with a case fatality rate above 40%. Similarly, H7N9 can infect humans, with a case fatality rate of over 40%. Since 1996, there have been several HPAI outbreaks affecting humans, emphasizing the need for safe and effective antivirals. We show that probenecid potently inhibits H5N1 and H7N9 replication in prophylactically or therapeutically treated A549 cells and normal human broncho-epithelial (NHBE) cells, and H5N1 replication in VeroE6 cells and mice.
MeSH term(s)	Animals ; Humans ; Mice ; Influenza, Human ; Influenza in Birds/drug therapy ; Influenza in Birds/prevention & control ; Influenza in Birds/epidemiology ; Influenza A Virus, H7N9 Subtype/genetics ; Influenza A Virus, H5N1 Subtype ; Probenecid ; Birds ; Mammals
Chemical Substances	Probenecid (PO572Z7917)
Language	English
Publishing date	2024-01-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v16010152
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Article: Silver nanotriangle array based LSPR sensor for rapid coronavirus detection.

Yang, Yanjun / Murray, Jackelyn / Haverstick, James / Tripp, Ralph A / Zhao, Yiping

Sensors and actuators. B, Chemical

2022 Volume 359, Page(s) 131604

Abstract: A rapid, portable, and cost-effective method to detect the infection of SARS-CoV-2 is fundamental toward mitigating the ... ...

Abstract	A rapid, portable, and cost-effective method to detect the infection of SARS-CoV-2 is fundamental toward mitigating the current
Language	English
Publishing date	2022-02-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1021505-0
ISSN	0925-4005
ISSN	0925-4005
DOI	10.1016/j.snb.2022.131604
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Article ; Online: Immunogenicity and protective efficacy of an RSV G S177Q central conserved domain nanoparticle vaccine.

Bergeron, Harrison C / Murray, Jackelyn / Juarez, Maria G / Nangle, Samuel J / DuBois, Rebecca M / Tripp, Ralph A

Frontiers in immunology

2023 Volume 14, Page(s) 1215323

Abstract: Introduction: Respiratory syncytial virus (RSV) can cause lower respiratory tract disease in infants and elderly populations. Despite decades of research, there remains no safe and approved RSV vaccine. Previously, we showed that an RSV G glycoprotein ... ...

Abstract	Introduction: Respiratory syncytial virus (RSV) can cause lower respiratory tract disease in infants and elderly populations. Despite decades of research, there remains no safe and approved RSV vaccine. Previously, we showed that an RSV G glycoprotein subunit vaccine candidate with a single point mutation within the central conserved domain (CCD), i.e. S177Q, considerably improved immunogenicity. Methods: Here, we examine the development of nanoparticle (NP) vaccines having either an RSV G protein CCD with wild-type sequence (NPWT) or an S177Q mutation (NP-S177Q). The NP vaccine immunogens were adjuvanted with monophosphoryl lipid A (MPLA), a TLR4 agonist to improve Th1- type responses. BALB/c mice were primed with 10 μg of NP-WT vaccine, NPS177Q, or vehicle, rested, and then boosted with a high (25 μg) or low (10 μg) dose of the NP-WT or NP-S177Q homologous candidate and subsequently challenged with RSV A2. Results: The results showed that mice boosted with NP-S177Q developed superior immunogenicity and neutralizing antibodies compared to NP-WT boosting. IgG from either NP-S177Q or NP-WT vaccinated mice did not interfere with fractalkine (CX3CL1) binding to CX3CR1 and effectively blocked G protein CX3C-CX3CR1 binding. Both NP-WT and NP-S177Q vaccination induced similar neutralizing antibodies to RSV in challenged mice compared to vehicle control. NP-S177Q boosting improved correlates of protection including reduced BAL cell infiltration following RSV challenge. However, the NP vaccine platform will require improvement due to the poor solubility and the unexpectedly weaker Th1-type IgG2a response. Discussion: The results from this study support further NP-S177Q vaccine candidate development.
MeSH term(s)	Mice ; Animals ; Respiratory Syncytial Virus Infections ; Respiratory Syncytial Virus Vaccines ; Antibodies, Viral ; Respiratory Syncytial Virus, Human/genetics ; Antibodies, Neutralizing ; GTP-Binding Proteins
Chemical Substances	Respiratory Syncytial Virus Vaccines ; Antibodies, Viral ; Antibodies, Neutralizing ; GTP-Binding Proteins (EC 3.6.1.-)
Language	English
Publishing date	2023-06-29
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1215323
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: MicroRNAs affect GPCR and Ion channel genes needed for influenza replication.

Orr-Burks, Nichole / Murray, Jackelyn / Todd, Kyle V / Bakre, Abhijeet / Tripp, Ralph A

The Journal of general virology

2021 Volume 102, Issue 11

Abstract: Influenza virus causes seasonal epidemics and sporadic pandemics resulting in morbidity, mortality, and economic losses worldwide. Understanding how to regulate influenza virus replication is important for developing vaccine and therapeutic strategies. ... ...

Abstract	Influenza virus causes seasonal epidemics and sporadic pandemics resulting in morbidity, mortality, and economic losses worldwide. Understanding how to regulate influenza virus replication is important for developing vaccine and therapeutic strategies. Identifying microRNAs (miRs) that affect host genes used by influenza virus for replication can support an antiviral strategy. In this study, G-protein coupled receptor (GPCR) and ion channel (IC) host genes in human alveolar epithelial (A549) cells used by influenza virus for replication (Orr-Burks
MeSH term(s)	A549 Cells ; Host-Pathogen Interactions ; Humans ; Influenza A virus/genetics ; Influenza A virus/physiology ; Influenza, Human/genetics ; Influenza, Human/metabolism ; Influenza, Human/prevention & control ; Ion Channels/genetics ; Ion Channels/metabolism ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Receptors, G-Protein-Coupled/genetics ; Receptors, G-Protein-Coupled/metabolism ; Virus Replication
Chemical Substances	Ion Channels ; MicroRNAs ; Receptors, G-Protein-Coupled
Language	English
Publishing date	2021-11-17
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	219316-4
ISSN	1465-2099 ; 0022-1317
ISSN (online)	1465-2099
ISSN	0022-1317
DOI	10.1099/jgv.0.001691
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Article ; Online: Probenecid Inhibits Respiratory Syncytial Virus (RSV) Replication.

Murray, Jackelyn / Bergeron, Harrison C / Jones, Les P / Reener, Zachary Beau / Martin, David E / Sancilio, Fred D / Tripp, Ralph A

Viruses

2022 Volume 14, Issue 5

Abstract: RNA viruses like SARS-CoV-2, influenza virus, and respiratory syncytial virus (RSV) are dependent on host genes for replication. We investigated if probenecid, an FDA-approved and safe urate-lowering drug that inhibits organic anion transporters (OATs) ... ...

Abstract	RNA viruses like SARS-CoV-2, influenza virus, and respiratory syncytial virus (RSV) are dependent on host genes for replication. We investigated if probenecid, an FDA-approved and safe urate-lowering drug that inhibits organic anion transporters (OATs) has prophylactic or therapeutic efficacy to inhibit RSV replication in three epithelial cell lines used in RSV studies, i.e., Vero E6 cells, HEp-2 cells, and in primary normal human bronchoepithelial (NHBE) cells, and in BALB/c mice. The studies showed that nanomolar concentrations of all probenecid regimens prevent RSV strain A and B replication in vitro and RSV strain A in vivo, representing a potential prophylactic and chemotherapeutic for RSV.
MeSH term(s)	Animals ; COVID-19 ; Mice ; Probenecid/pharmacology ; Probenecid/therapeutic use ; Respiratory Syncytial Virus Infections/drug therapy ; Respiratory Syncytial Virus Infections/metabolism ; Respiratory Syncytial Virus Infections/prevention & control ; Respiratory Syncytial Virus, Human/genetics ; SARS-CoV-2 ; Virus Replication
Chemical Substances	Probenecid (PO572Z7917)
Language	English
Publishing date	2022-04-27
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v14050912
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Article ; Online: Rapid and quantitative detection of respiratory viruses using surface-enhanced Raman spectroscopy and machine learning.

Yang, Yanjun / Xu, Beibei / Murray, Jackelyn / Haverstick, James / Chen, Xianyan / Tripp, Ralph A / Zhao, Yiping

Biosensors & bioelectronics

2022 Volume 217, Page(s) 114721

Abstract: Rapid and sensitive pathogen detection is important for prevention and control of disease. Here, we report a label-free diagnostic platform that combines surface-enhanced Raman scattering (SERS) and machine learning for the rapid and accurate detection ... ...

Abstract	Rapid and sensitive pathogen detection is important for prevention and control of disease. Here, we report a label-free diagnostic platform that combines surface-enhanced Raman scattering (SERS) and machine learning for the rapid and accurate detection of thirteen respiratory virus species including SARS-CoV-2, common human coronaviruses, influenza viruses, and others. Virus detection and measurement have been performed using highly sensitive SiO
MeSH term(s)	Biosensing Techniques ; COVID-19/diagnosis ; Humans ; Machine Learning ; SARS-CoV-2 ; Silicon Dioxide ; Silver/chemistry ; Spectrum Analysis, Raman/methods
Chemical Substances	Silver (3M4G523W1G) ; Silicon Dioxide (7631-86-9)
Language	English
Publishing date	2022-09-15
Publishing country	England
Document type	Journal Article
ZDB-ID	1011023-9
ISSN	1873-4235 ; 0956-5663
ISSN (online)	1873-4235
ISSN	0956-5663
DOI	10.1016/j.bios.2022.114721
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Article ; Online: Drug repositioning of Clopidogrel or Triamterene to inhibit influenza virus replication in vitro

Nichole Orr-Burks / Jackelyn Murray / Kyle V. Todd / Abhijeet Bakre / Ralph A. Tripp

PLoS ONE, Vol 16, Iss

2021 Volume 10

Abstract: Influenza viruses cause respiratory tract infections and substantial health concerns. Infection may result in mild to severe respiratory disease associated with morbidity and some mortality. Several anti-influenza drugs are available, but these agents ... ...

Abstract	Influenza viruses cause respiratory tract infections and substantial health concerns. Infection may result in mild to severe respiratory disease associated with morbidity and some mortality. Several anti-influenza drugs are available, but these agents target viral components and are susceptible to drug resistance. There is a need for new antiviral drug strategies that include repurposing of clinically approved drugs. Drugs that target cellular machinery necessary for influenza virus replication can provide a means for inhibiting influenza virus replication. We used RNA interference screening to identify key host cell genes required for influenza replication, and then FDA-approved drugs that could be repurposed for targeting host genes. We examined the effects of Clopidogrel and Triamterene to inhibit A/WSN/33 (EC50 5.84 uM and 31.48 uM, respectively), A/CA/04/09 (EC50 6.432 uM and 3.32 uM, respectively), and B/Yamagata/16/1988 (EC50 0.28 uM and 0.11 uM, respectively) replication. Clopidogrel and Triamterene provide a druggable approach to influenza treatment across multiple strains and subtypes.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Drug repositioning of Clopidogrel or Triamterene to inhibit influenza virus replication in vitro.

Nichole Orr-Burks / Jackelyn Murray / Kyle V Todd / Abhijeet Bakre / Ralph A Tripp

PLoS ONE, Vol 16, Iss 10, p e

2021 Volume 0259129

Abstract	Influenza viruses cause respiratory tract infections and substantial health concerns. Infection may result in mild to severe respiratory disease associated with morbidity and some mortality. Several anti-influenza drugs are available, but these agents target viral components and are susceptible to drug resistance. There is a need for new antiviral drug strategies that include repurposing of clinically approved drugs. Drugs that target cellular machinery necessary for influenza virus replication can provide a means for inhibiting influenza virus replication. We used RNA interference screening to identify key host cell genes required for influenza replication, and then FDA-approved drugs that could be repurposed for targeting host genes. We examined the effects of Clopidogrel and Triamterene to inhibit A/WSN/33 (EC50 5.84 uM and 31.48 uM, respectively), A/CA/04/09 (EC50 6.432 uM and 3.32 uM, respectively), and B/Yamagata/16/1988 (EC50 0.28 uM and 0.11 uM, respectively) replication. Clopidogrel and Triamterene provide a druggable approach to influenza treatment across multiple strains and subtypes.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: G-Protein-Coupled Receptor and Ion Channel Genes Used by Influenza Virus for Replication.

Orr-Burks, Nichole / Murray, Jackelyn / Todd, Kyle V / Bakre, Abhijeet / Tripp, Ralph A

Journal of virology

2021 Volume 95, Issue 9

Abstract: Influenza virus causes epidemics and sporadic pandemics resulting in morbidity, mortality, and economic losses. Influenza viruses require host genes to replicate. RNA interference (RNAi) screens can identify host genes coopted by influenza virus for ... ...

Abstract	Influenza virus causes epidemics and sporadic pandemics resulting in morbidity, mortality, and economic losses. Influenza viruses require host genes to replicate. RNA interference (RNAi) screens can identify host genes coopted by influenza virus for replication. Targeting these proinfluenza genes can provide therapeutic strategies to reduce virus replication. Nineteen proinfluenza G-protein-coupled receptor (GPCR) and 13 proinfluenza ion channel genes were identified in human lung (A549) cells by use of small interfering RNAs (siRNAs). These proinfluenza genes were authenticated by testing influenza virus A/WSN/33-, A/CA/04/09-, and B/Yamagata/16/1988-infected A549 cells, resulting in the validation of 16 proinfluenza GPCR and 5 proinfluenza ion channel genes. These findings showed that several GPCR and ion channel genes are needed for the production of infectious influenza virus. These data provide potential targets for the development of host-directed therapeutic strategies to impede the influenza virus productive cycle so as to limit infection.
MeSH term(s)	A549 Cells ; Animals ; Dogs ; Host Microbial Interactions ; Humans ; Influenza A Virus, H1N1 Subtype/physiology ; Influenza B virus/physiology ; Influenza, Human/virology ; Ion Channels/metabolism ; Madin Darby Canine Kidney Cells ; Receptors, G-Protein-Coupled/metabolism ; Virus Replication
Chemical Substances	Ion Channels ; Receptors, G-Protein-Coupled
Language	English
Publishing date	2021-04-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.02410-20
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 609: Show issues

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ab Jg. 2022: Lesesaal (EG)

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