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Article ; Online: Postinfection Metabolic Reprogramming of the Murine Trigeminal Ganglion Limits Herpes Simplex Virus-1 Replication.

Patil, Chandrashekhar D / Suryawanshi, Rahul K / Kapoor, Divya / Shukla, Deepak

2022 Volume 13, Issue 5, Page(s) e0219422

Abstract: Herpes simplex virus type-1 (HSV-1) infections are known to alter the host metabolism for efficient ... ...

Abstract	Herpes simplex virus type-1 (HSV-1) infections are known to alter the host metabolism for efficient propagation
MeSH term(s)	Mice ; Animals ; Herpesvirus 1, Human/physiology ; Trigeminal Ganglion ; Keratitis, Herpetic ; Herpes Simplex ; Virus Replication ; Cornea ; Polyamines ; Carbon ; Nucleotides ; Virus Latency/physiology
Chemical Substances	Polyamines ; Carbon (7440-44-0) ; Nucleotides
Language	English
Publishing date	2022-08-31
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mbio.02194-22
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Pathophysiology of reinfection by exogenous HSV-1 is driven by heparanase dysfunction.

Suryawanshi, Rahul K / Patil, Chandrashekhar D / Agelidis, Alex / Koganti, Raghuram / Yadavalli, Tejabhiram / Ames, Joshua M / Borase, Hemant / Shukla, Deepak

Science advances

2023 Volume 9, Issue 17, Page(s) eadf3977

Abstract: Limited knowledge exists on exogenous DNA virus reinfections. Herpes simplex virus-1 (HSV-1), a prototype DNA virus, causes multiple human diseases including vision-threatening eye infections. While reinfection with an exogenous HSV-1 strain is ... ...

Abstract	Limited knowledge exists on exogenous DNA virus reinfections. Herpes simplex virus-1 (HSV-1), a prototype DNA virus, causes multiple human diseases including vision-threatening eye infections. While reinfection with an exogenous HSV-1 strain is considered plausible, little is known about the underlying mechanisms governing its pathophysiology in a host. Heparanase (HPSE), a host endoglycosidase, when up-regulated by HSV-1 infection dictates local inflammatory response by destabilizing tissue architecture. Here, we demonstrate that HSV-1 reinfection in mice causes notable pathophysiology in wild-type controls compared to the animals lacking HPSE. The endoglycosidase promotes infected cell survival and supports a pro-disease environment. In contrast, lack of HPSE strengthens intrinsic immunity by promoting cytokine expression, inducing necroptosis of infected cells, and decreasing leukocyte infiltration into the cornea. Collectively, we report that immunity from a recent prior infection fails to abolish disease manifestation during HSV-1 reinfection unless HPSE is rendered inactive.
MeSH term(s)	Humans ; Animals ; Mice ; Herpesvirus 1, Human ; Reinfection ; Herpes Simplex ; Glucuronidase/genetics ; Glucuronidase/metabolism
Chemical Substances	heparanase (EC 3.2.1.-) ; Glucuronidase (EC 3.2.1.31)
Language	English
Publishing date	2023-04-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.adf3977
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Article ; Online: Mercapto-pyrimidines are reversible covalent inhibitors of the papain-like protease (PLpro) and inhibit SARS-CoV-2 (SCoV-2) replication.

Bajaj, Teena / Wehri, Eddie / Suryawanshi, Rahul K / King, Elizabeth / Pardeshi, Kundan Singh / Behrouzi, Kamyar / Khodabakhshi, Zahra / Schulze-Gahmen, Ursula / Kumar, G Renuka / Mofrad, Mohammad R K / Nomura, Daniel K / Ott, Melanie / Schaletzky, Julia / Murthy, Niren

RSC advances

2023 Volume 13, Issue 26, Page(s) 17667–17677

Abstract: The papain-like protease (PLpro) plays a critical role in SARS-CoV-2 (SCoV-2) pathogenesis and is essential for viral replication and for allowing the virus to evade the host immune response. Inhibitors of PLpro have great therapeutic potential, however, ...

Abstract	The papain-like protease (PLpro) plays a critical role in SARS-CoV-2 (SCoV-2) pathogenesis and is essential for viral replication and for allowing the virus to evade the host immune response. Inhibitors of PLpro have great therapeutic potential, however, developing them has been challenging due to PLpro's restricted substrate binding pocket. In this report, we screened a 115 000-compound library for PLpro inhibitors and identified a new pharmacophore, based on a mercapto-pyrimidine fragment that is a reversible covalent inhibitor (RCI) of PLpro and inhibits viral replication in cells. Compound 5 had an IC
Language	English
Publishing date	2023-06-12
Publishing country	England
Document type	Journal Article
ISSN	2046-2069
ISSN (online)	2046-2069
DOI	10.1039/d3ra01915b
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Article: Heparan Sulfate Binding Cationic Peptides Restrict SARS-CoV-2 Entry.

Suryawanshi, Rahul K / Patil, Chandrashekhar D / Koganti, Raghuram / Singh, Sudhanshu Kumar / Ames, Joshua M / Shukla, Deepak

Pathogens (Basel, Switzerland)

2021 Volume 10, Issue 7

Abstract: A novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. While the world is striving for a treatment modality against SARS-CoV-2, our understanding about the virus entry mechanisms may help to design entry ... ...

Abstract	A novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. While the world is striving for a treatment modality against SARS-CoV-2, our understanding about the virus entry mechanisms may help to design entry inhibitors, which may help to limit the virus spreading. Owing to the importance of cellular ACE2 and heparan sulfate in SARS-CoV-2 entry, we aimed to evaluate the efficacy of cationic G1 and G2 peptides in virus entry inhibition. In silico binding affinity studies revealed possible binding sites of G1 and G2 peptides on HS and ACE2, which are required for the spike-HS and spike-ACE2 interactions. Prophylactic treatment of G1 and G2 peptide was also proved to decrease the cell surface HS, an essential virus entry receptor. With these two mechanisms we confirm the possible use of cationic peptides to inhibit the entry of SARS-CoV-2.
Language	English
Publishing date	2021-06-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens10070803
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Article ; Online: Dissociation of DNA damage sensing by endoglycosidase HPSE.

Agelidis, Alex / Suryawanshi, Rahul K / Patil, Chandrashekhar D / Campeau, Anaamika / Gonzalez, David J / Shukla, Deepak

iScience

2021 Volume 24, Issue 3, Page(s) 102242

Abstract: Balance between cell proliferation and elimination is critical in handling threats both exogenous and of internal dysfunction. Recent work has implicated a conserved but poorly understood endoglycosidase heparanase (HPSE) in the restriction of innate ... ...

Abstract	Balance between cell proliferation and elimination is critical in handling threats both exogenous and of internal dysfunction. Recent work has implicated a conserved but poorly understood endoglycosidase heparanase (HPSE) in the restriction of innate defense responses, yet biochemical mediators of these key functions remained unclear. Here, an unbiased immunopurification proteomics strategy is employed to identify and rank uncharacterized interactions between HPSE and mediators of canonical signaling pathways linking cell cycle and stress responses. We demonstrate with models of genotoxic stress including herpes simplex virus infection and chemotherapeutic treatment that HPSE dampens innate responses to double-stranded DNA breakage by interfering with signal transduction between initial sensors and downstream mediators. Given the long-standing recognition of HPSE in driving late-stage inflammatory disease exemplified by tissue destruction and cancer metastasis, modulation of this protein with control over the DNA damage response imparts a unique strategy in the development of unconventional multivalent therapy.
Language	English
Publishing date	2021-02-27
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2021.102242
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Article ; Online: Pathological processes activated by herpes simplex virus-1 (HSV-1) infection in the cornea.

Koujah, Lulia / Suryawanshi, Rahul K / Shukla, Deepak

Cellular and molecular life sciences : CMLS

2018 Volume 76, Issue 3, Page(s) 405–419

Abstract: Herpes simplex virus type-1 (HSV-1) is a ubiquitous pathogen that infects a large majority of the human population worldwide. It is also a leading cause of infection-related blindness in the developed world. HSV-1 infection of the cornea begins with ... ...

Abstract	Herpes simplex virus type-1 (HSV-1) is a ubiquitous pathogen that infects a large majority of the human population worldwide. It is also a leading cause of infection-related blindness in the developed world. HSV-1 infection of the cornea begins with viral entry into resident cells via a multistep process that involves interaction of viral glycoproteins and host cell surface receptors. Once inside, HSV-1 infection induces a chronic immune-inflammatory response resulting in corneal scarring, thinning and neovascularization. This leads to development of various ocular diseases such as herpes stromal keratitis, resulting in visual impairment and eventual blindness. HSV-1 can also invade the central nervous system and lead to encephalitis, a relatively common cause of sporadic fetal encephalitis worldwide. In this review, we discuss the pathological processes activated by corneal HSV-1 infection and existing antiviral therapies as well as novel therapeutic options currently under development.
MeSH term(s)	Antiviral Agents/therapeutic use ; Cornea/chemistry ; Cornea/physiopathology ; Cornea/virology ; Corneal Diseases/drug therapy ; Corneal Diseases/pathology ; Corneal Diseases/virology ; Glycoproteins/metabolism ; Herpes Simplex/drug therapy ; Herpes Simplex/pathology ; Herpesvirus 1, Human/metabolism ; Host-Pathogen Interactions ; Humans ; Models, Biological ; Receptors, Cell Surface/metabolism
Chemical Substances	Antiviral Agents ; Glycoproteins ; Receptors, Cell Surface
Language	English
Publishing date	2018-10-16
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-018-2938-1
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Article ; Online: The Complete Mitochondrial Genome of the Fivespot Flounder, Pseudorhombus pentophthalmus (Pleuronectiformes: Paralichthyidae), from Korea and Its Phylogenetic Analysis

Lee, Yong Suk / Patil, Maheshkumar Prakash / Kim, Jong-Oh / Lee, Yu-Jin / Seo, Yong Bae / Kim, Jin-Koo / Suryawanshi, Rahul K. / Kim, Gun-Do

Fishes. 2023 Mar. 02, v. 8, no. 3

2023

Abstract: The mitogenome is an important tool for researching the evolution of metazoan animals. However, until now, only few mitochondrial genes of Pseudorhombus pentophthalmus have been reported. Here, we report the complete mitogenome of P. pentophthalmus, ... ...

Abstract	The mitogenome is an important tool for researching the evolution of metazoan animals. However, until now, only few mitochondrial genes of Pseudorhombus pentophthalmus have been reported. Here, we report the complete mitogenome of P. pentophthalmus, assembled using the Illumina platform. The circular mitogenome of P. pentophthalmus is 16,684 bp in length, has a bias A+T content of 52.78%, encodes 37 genes (13 protein-coding genes, 22 tRNA genes, 2 rRNA genes), and has a control region. The overall nucleotide composition was A: 26.56%, T: 26.22%, G: 17.97%, and C: 29.25%. The phylogenetic tree based on the complete mitogenome P. pentophthalmus was shown to be monophyletic with the other Pseudorhombus species and was shown to be on the same branch as P. dupliciocellatus. This research might be useful for future studies on population genetics and evolution analysis.
Keywords	Pseudorhombus ; flounder ; mitochondria ; mitochondrial genome ; monophyly ; population genetics ; Korean Peninsula
Language	English
Dates of publication	2023-0302
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article ; Online
ISSN	2410-3888
DOI	10.3390/fishes8030150
Database	NAL-Catalogue (AGRICOLA)

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Article: Heparan Sulfate Binding Cationic Peptides Restrict SARS-CoV-2 Entry

Suryawanshi, Rahul K. / Patil, Chandrashekhar D. / Koganti, Raghuram / Singh, Sudhanshu Kumar / Ames, Joshua M. / Shukla, Deepak

Pathogens. 2021 June 24, v. 10, no. 7

2021

Abstract	A novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. While the world is striving for a treatment modality against SARS-CoV-2, our understanding about the virus entry mechanisms may help to design entry inhibitors, which may help to limit the virus spreading. Owing to the importance of cellular ACE2 and heparan sulfate in SARS-CoV-2 entry, we aimed to evaluate the efficacy of cationic G1 and G2 peptides in virus entry inhibition. In silico binding affinity studies revealed possible binding sites of G1 and G2 peptides on HS and ACE2, which are required for the spike–HS and spike–ACE2 interactions. Prophylactic treatment of G1 and G2 peptide was also proved to decrease the cell surface HS, an essential virus entry receptor. With these two mechanisms we confirm the possible use of cationic peptides to inhibit the entry of SARS-CoV-2.
Keywords	Severe acute respiratory syndrome coronavirus 2 ; computer simulation ; disease prevention ; heparan sulfate ; pandemic ; peptides ; viruses
Language	English
Dates of publication	2021-0624
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens10070803
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Dysregulation of Cell Signaling by SARS-CoV-2.

Suryawanshi, Rahul K / Koganti, Raghuram / Agelidis, Alex / Patil, Chandrashekhar D / Shukla, Deepak

Trends in microbiology

2020 Volume 29, Issue 3, Page(s) 224–237

Abstract: Pathogens usurp host pathways to generate a permissive environment for their propagation. The current spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection presents the urgent need to understand the complex pathogen-host ... ...

Abstract	Pathogens usurp host pathways to generate a permissive environment for their propagation. The current spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection presents the urgent need to understand the complex pathogen-host interplay for effective control of the virus. SARS-CoV-2 reorganizes the host cytoskeleton for efficient cell entry and controls host transcriptional processes to support viral protein translation. The virus also dysregulates innate cellular defenses using various structural and nonstructural proteins. This results in substantial but delayed hyperinflammation alongside a weakened interferon (IFN) response. We provide an overview of SARS-CoV-2 and its uniquely aggressive life cycle and discuss the interactions of various viral proteins with host signaling pathways. We also address the functional changes in SARS-CoV-2 proteins, relative to SARS-CoV. Our comprehensive assessment of host signaling in SARS-CoV-2 pathogenesis provides some complex yet important strategic clues for the development of novel therapeutics against this rapidly emerging worldwide crisis.
MeSH term(s)	COVID-19/metabolism ; COVID-19/virology ; Humans ; Immunity/physiology ; Life Cycle Stages ; SARS-CoV-2/pathogenicity ; Signal Transduction/physiology ; Viral Proteins/genetics ; Viral Proteins/metabolism
Chemical Substances	Viral Proteins
Language	English
Publishing date	2020-12-19
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	1158963-2
ISSN	1878-4380 ; 0966-842X
ISSN (online)	1878-4380
ISSN	0966-842X
DOI	10.1016/j.tim.2020.12.007
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Article: Pathological processes activated by herpes simplex virus-1 (HSV-1) infection in the cornea

Koujah, Lulia / Suryawanshi, Rahul K / Shukla, Deepak

Cellular and molecular life sciences. 2019 Feb., v. 76, no. 3

2019

Abstract	Herpes simplex virus type-1 (HSV-1) is a ubiquitous pathogen that infects a large majority of the human population worldwide. It is also a leading cause of infection-related blindness in the developed world. HSV-1 infection of the cornea begins with viral entry into resident cells via a multistep process that involves interaction of viral glycoproteins and host cell surface receptors. Once inside, HSV-1 infection induces a chronic immune-inflammatory response resulting in corneal scarring, thinning and neovascularization. This leads to development of various ocular diseases such as herpes stromal keratitis, resulting in visual impairment and eventual blindness. HSV-1 can also invade the central nervous system and lead to encephalitis, a relatively common cause of sporadic fetal encephalitis worldwide. In this review, we discuss the pathological processes activated by corneal HSV-1 infection and existing antiviral therapies as well as novel therapeutic options currently under development.
Keywords	central nervous system ; Human alphaherpesvirus 1 ; glycoproteins ; blindness ; receptors ; therapeutics ; cornea ; viruses ; encephalitis ; human population ; keratitis ; herpes simplex ; angiogenesis ; pathogens
Language	English
Dates of publication	2019-02
Size	p. 405-419.
Publishing place	Springer International Publishing
Document type	Article
Note	Review ; 2019-12-06
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-018-2938-1
Database	NAL-Catalogue (AGRICOLA)

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