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Article ; Online: Ginkgolic acid inhibits orthopneumo- and metapneumo- virus infectivity.

Luck, Maria I / Subillaga, Erick J / Borenstein, Ronen / Sabo, Yosef

2024 Volume 14, Issue 1, Page(s) 8230

Abstract: The human respiratory syncytial virus (hRSV) and the human metapneumovirus (hMPV) are important human respiratory pathogens from the Pneumoviridae family. Both are responsible for severe respiratory tract infections in infants, young children, elderly ... ...

Abstract	The human respiratory syncytial virus (hRSV) and the human metapneumovirus (hMPV) are important human respiratory pathogens from the Pneumoviridae family. Both are responsible for severe respiratory tract infections in infants, young children, elderly individuals, adults with chronic medical conditions, and immunocompromised patients. Despite their large impact on human health, vaccines for hRSV were only recently introduced, and only limited treatment options exist. Here we show that Ginkgolic acid (GA), a natural compound from the extract of Ginkgo biloba, with known antiviral properties for several viruses, efficiently inhibits these viruses' infectivity and spread in cultures in a dose-dependent manner. We demonstrate that the drug specifically affects the entry step during the early stages on the viruses' life cycle with no effect on post-entry and late stage events, including viral gene transcription, genome replication, assembly and particles release. We provide evidence that GA acts as an efficient antiviral for members of the Pneumoviridae family and has the potential to be used to treat acute infections.
MeSH term(s)	Child ; Adult ; Infant ; Humans ; Child, Preschool ; Aged ; Paramyxoviridae Infections ; Metapneumovirus/genetics ; Respiratory Tract Infections ; Respiratory Syncytial Virus, Human/genetics ; Virus Diseases ; Respiratory Syncytial Virus Infections ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Salicylates
Chemical Substances	ginkgolic acid (22910-60-7) ; Antiviral Agents ; Salicylates
Language	English
Publishing date	2024-04-08
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/s41598-024-58032-8
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Herpes Simplex Virus, Human Papillomavirus, and Cervical Cancer: Overview, Relationship, and Treatment Implications.

Sausen, Daniel G / Shechter, Oren / Gallo, Elisa S / Dahari, Harel / Borenstein, Ronen

Cancers

2023 Volume 15, Issue 14

Abstract: There is a significant body of research examining the role of human papillomavirus (HPV) in the pathogenesis of cervical cancer, with a particular emphasis on the oncogenic proteins E5, E6, and E7. What is less well explored, however, is the relationship ...

Abstract	There is a significant body of research examining the role of human papillomavirus (HPV) in the pathogenesis of cervical cancer, with a particular emphasis on the oncogenic proteins E5, E6, and E7. What is less well explored, however, is the relationship between cervical cancer and herpes simplex virus (HSV). To date, studies examining the role of HSV in cervical cancer pathogenesis have yielded mixed results. While several experiments have determined that HPV/HSV-2 coinfection results in a higher risk of developing cervical cancer, others have questioned the validity of this association. However, clarifying the potential role of HSV in the pathogenesis of cervical cancer may have significant implications for both the prevention and treatment of this disease. Should this relationship be clarified, treating and preventing HSV could open another avenue with which to prevent cervical cancer. The importance of this is highlighted by the fact that, despite the creation of an effective vaccine against HPV, cervical cancer still impacts 604,000 women and is responsible for 342,000 deaths annually. This review provides an overview of HSV and HPV infections and then delves into the possible links between HPV, HSV, and cervical cancer. It concludes with a summary of preventive measures against and recent treatment advances in cervical cancer.
Language	English
Publishing date	2023-07-20
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15143692
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Multifaceted Role of AMPK in Viral Infections.

Bhutta, Maimoona Shahid / Gallo, Elisa S / Borenstein, Ronen

Cells

2021 Volume 10, Issue 5

Abstract: Viral pathogens often exploit host cell regulatory and signaling pathways to ensure an optimal environment for growth and survival. Several studies have suggested that 5'-adenosine monophosphate-activated protein kinase (AMPK), an intracellular serine/ ... ...

Abstract	Viral pathogens often exploit host cell regulatory and signaling pathways to ensure an optimal environment for growth and survival. Several studies have suggested that 5'-adenosine monophosphate-activated protein kinase (AMPK), an intracellular serine/threonine kinase, plays a significant role in the modulation of infection. Traditionally, AMPK is a key energy regulator of cell growth and proliferation, host autophagy, stress responses, metabolic reprogramming, mitochondrial homeostasis, fatty acid β-oxidation and host immune function. In this review, we highlight the modulation of host AMPK by various viruses under physiological conditions. These intracellular pathogens trigger metabolic changes altering AMPK signaling activity that then facilitates or inhibits viral replication. Considering the COVID-19 pandemic, understanding the regulation of AMPK signaling following infection can shed light on the development of more effective therapeutic strategies against viral infectious diseases.
MeSH term(s)	AMP-Activated Protein Kinases/metabolism ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Autophagy/drug effects ; Autophagy/immunology ; COVID-19/epidemiology ; COVID-19/immunology ; Cell Proliferation/drug effects ; Drug Development ; Humans ; Pandemics/prevention & control ; SARS-CoV-2/immunology ; Signal Transduction/drug effects ; Signal Transduction/immunology ; Virus Diseases/drug therapy ; Virus Diseases/immunology ; Virus Replication/drug effects ; Virus Replication/immunology ; COVID-19 Drug Treatment
Chemical Substances	Antiviral Agents ; AMP-Activated Protein Kinases (EC 2.7.11.31)
Language	English
Publishing date	2021-05-06
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells10051118
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Article ; Online: Multifaceted Role of AMPK in Viral Infections

Maimoona Shahid Bhutta / Elisa S. Gallo / Ronen Borenstein

Cells, Vol 10, Iss 1118, p

2021 Volume 1118

Abstract: Viral pathogens often exploit host cell regulatory and signaling pathways to ensure an optimal environment for growth and survival. Several studies have suggested that 5′-adenosine monophosphate-activated protein kinase (AMPK), an intracellular serine/ ... ...

Abstract	Viral pathogens often exploit host cell regulatory and signaling pathways to ensure an optimal environment for growth and survival. Several studies have suggested that 5′-adenosine monophosphate-activated protein kinase (AMPK), an intracellular serine/threonine kinase, plays a significant role in the modulation of infection. Traditionally, AMPK is a key energy regulator of cell growth and proliferation, host autophagy, stress responses, metabolic reprogramming, mitochondrial homeostasis, fatty acid β-oxidation and host immune function. In this review, we highlight the modulation of host AMPK by various viruses under physiological conditions. These intracellular pathogens trigger metabolic changes altering AMPK signaling activity that then facilitates or inhibits viral replication. Considering the COVID-19 pandemic, understanding the regulation of AMPK signaling following infection can shed light on the development of more effective therapeutic strategies against viral infectious diseases.
Keywords	AMPK ; virus ; COVID-19 ; catabolic process ; anabolic processes ; autophagy ; Biology (General) ; QH301-705.5
Subject code	570 ; 572
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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Article ; Online: Epstein-Barr Virus (EBV) Epithelial Associated Malignancies: Exploring Pathologies and Current Treatments.

Shechter, Oren / Sausen, Daniel G / Gallo, Elisa S / Dahari, Harel / Borenstein, Ronen

International journal of molecular sciences

2022 Volume 23, Issue 22

Abstract: Epstein-Barr virus (EBV) is one of eight known herpesviruses with the potential to infect humans. Globally, it is estimated that between 90-95% of the population has been infected with EBV. EBV is an oncogenic virus that has been strongly linked to ... ...

Abstract	Epstein-Barr virus (EBV) is one of eight known herpesviruses with the potential to infect humans. Globally, it is estimated that between 90-95% of the population has been infected with EBV. EBV is an oncogenic virus that has been strongly linked to various epithelial malignancies such as nasopharyngeal and gastric cancer. Recent evidence suggests a link between EBV and breast cancer. Additionally, there are other, rarer cancers with weaker evidence linking them to EBV. In this review, we discuss the currently known epithelial malignancies associated with EBV. Additionally, we discuss and establish which treatments and therapies are most recommended for each cancer associated with EBV.
MeSH term(s)	Humans ; Herpesvirus 4, Human ; Epstein-Barr Virus Infections/complications ; Epstein-Barr Virus Infections/therapy ; Stomach Neoplasms ; Nasopharynx ; Neoplasms, Glandular and Epithelial
Language	English
Publishing date	2022-11-19
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms232214389
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Article ; Online: Stress-Induced Epstein-Barr Virus Reactivation.

Sausen, Daniel G / Bhutta, Maimoona S / Gallo, Elisa S / Dahari, Harel / Borenstein, Ronen

Biomolecules

2021 Volume 11, Issue 9

Abstract: Epstein-Barr virus (EBV) is typically found in a latent, asymptomatic state in immunocompetent individuals. Perturbations of the host immune system can stimulate viral reactivation. Furthermore, there are a myriad of EBV-associated illnesses including ... ...

Abstract	Epstein-Barr virus (EBV) is typically found in a latent, asymptomatic state in immunocompetent individuals. Perturbations of the host immune system can stimulate viral reactivation. Furthermore, there are a myriad of EBV-associated illnesses including various cancers, post-transplant lymphoproliferative disease, and autoimmune conditions. A thorough understanding of this virus, and the interplay between stress and the immune system, is essential to establish effective treatment. This review will provide a summary of the interaction between both psychological and cellular stressors resulting in EBV reactivation. It will examine mechanisms by which EBV establishes and maintains latency and will conclude with a brief overview of treatments targeting EBV.
MeSH term(s)	Animals ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Epstein-Barr Virus Infections/drug therapy ; Epstein-Barr Virus Infections/virology ; Herpesvirus 4, Human/drug effects ; Herpesvirus 4, Human/physiology ; Humans ; Oxidative Stress/drug effects ; Stress, Psychological/complications ; Virus Latency/drug effects ; Virus Latency/physiology
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2021-09-18
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom11091380
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Evasion of the Host Immune Response by Betaherpesviruses.

Sausen, Daniel G / Reed, Kirstin M / Bhutta, Maimoona S / Gallo, Elisa S / Borenstein, Ronen

International journal of molecular sciences

2021 Volume 22, Issue 14

Abstract: The human immune system boasts a diverse array of strategies for recognizing and eradicating invading pathogens. Human betaherpesviruses, a highly prevalent subfamily of viruses, include human cytomegalovirus (HCMV), human herpesvirus (HHV) 6A, HHV-6B, ... ...

Abstract	The human immune system boasts a diverse array of strategies for recognizing and eradicating invading pathogens. Human betaherpesviruses, a highly prevalent subfamily of viruses, include human cytomegalovirus (HCMV), human herpesvirus (HHV) 6A, HHV-6B, and HHV-7. These viruses have evolved numerous mechanisms for evading the host response. In this review, we will highlight the complex interplay between betaherpesviruses and the human immune response, focusing on protein function. We will explore methods by which the immune system first responds to betaherpesvirus infection as well as mechanisms by which viruses subvert normal cellular functions to evade the immune system and facilitate viral latency, persistence, and reactivation. Lastly, we will briefly discuss recent advances in vaccine technology targeting betaherpesviruses. This review aims to further elucidate the dynamic interactions between betaherpesviruses and the human immune system.
MeSH term(s)	Betaherpesvirinae/immunology ; Betaherpesvirinae/pathogenicity ; Herpesviridae Infections/immunology ; Herpesviridae Infections/virology ; Humans ; Immune Evasion ; Immunity
Language	English
Publishing date	2021-07-13
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22147503
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Article: Ginkgolic Acid Inhibits Coronavirus Strain 229E Infection of Human Epithelial Lung Cells.

Bhutta, Maimoona S / Sausen, Daniel G / Gallo, Elisa S / Dahari, Harel / Doncel, Gustavo F / Borenstein, Ronen

Pharmaceuticals (Basel, Switzerland)

2021 Volume 14, Issue 10

Abstract: Since December 2019, the COVID-19 pandemic has affected more than 200 million individuals around the globe and caused millions of deaths. Although there are now multiple vaccines for SARS-CoV-2, their efficacy may be limited by current and future viral ... ...

Abstract	Since December 2019, the COVID-19 pandemic has affected more than 200 million individuals around the globe and caused millions of deaths. Although there are now multiple vaccines for SARS-CoV-2, their efficacy may be limited by current and future viral mutations. Therefore, effective antiviral compounds are an essential component to win the battle against the family of coronaviruses. Ginkgolic Acid (GA) is a pan-antiviral molecule with proven effective in vitro and in vivo activity. We previously demonstrated that GA inhibits Herpes Simplex Virus 1 (HSV-1) by disrupting viral structure, blocking fusion, and inhibiting viral protein synthesis. Additionally, we reported that GA displays broad-spectrum fusion inhibition encompassing all three classes of fusion proteins, including those of HIV, Ebola, influenza A, and Epstein Barr virus. Here, we report that GA exhibited potent antiviral activity against Human Coronavirus strain 229E (HCoV-229E) infection of human epithelial lung cells (MRC-5). GA significantly reduced progeny virus production, expression of viral proteins, and cytopathic effects (CPE). Furthermore, GA significantly inhibited HCoV-229E even when added post-infection. In light of our findings and the similarities of this family of viruses, GA holds promising potential as an effective antiviral treatment for SARS-CoV-2.
Language	English
Publishing date	2021-09-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2193542-7
ISSN	1424-8247
ISSN	1424-8247
DOI	10.3390/ph14100980
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Article ; Online: Author Correction: Downregulation of CD40L-CD40 attenuates seizure susceptibility and severity of seizures.

Pototskiy, Esther / Vinokuroff, Katherine / Ojeda, Andrew / Major, C Kendall / Sharma, Deepak / Anderson, Taylor / Howard, Kendall / Borenstein, Ronen / Musto, Alberto E

Scientific reports

2021 Volume 11, Issue 1, Page(s) 23252

Language	English
Publishing date	2021-11-25
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/s41598-021-02005-8
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Hepatitis B and Hepatitis D Viruses: A Comprehensive Update with an Immunological Focus.

Sausen, Daniel G / Shechter, Oren / Bietsch, William / Shi, Zhenzhen / Miller, Samantha M / Gallo, Elisa S / Dahari, Harel / Borenstein, Ronen

International journal of molecular sciences

2022 Volume 23, Issue 24

Abstract: Hepatitis B virus (HBV) and hepatitis delta virus (HDV) are highly prevalent viruses estimated to infect approximately 300 million people and 12-72 million people worldwide, respectively. HDV requires the HBV envelope to establish a successful infection. ...

Abstract	Hepatitis B virus (HBV) and hepatitis delta virus (HDV) are highly prevalent viruses estimated to infect approximately 300 million people and 12-72 million people worldwide, respectively. HDV requires the HBV envelope to establish a successful infection. Concurrent infection with HBV and HDV can result in more severe disease outcomes than infection with HBV alone. These viruses can cause significant hepatic disease, including cirrhosis, fulminant hepatitis, and hepatocellular carcinoma, and represent a significant cause of global mortality. Therefore, a thorough understanding of these viruses and the immune response they generate is essential to enhance disease management. This review includes an overview of the HBV and HDV viruses, including life cycle, structure, natural course of infection, and histopathology. A discussion of the interplay between HDV RNA and HBV DNA during chronic infection is also included. It then discusses characteristics of the immune response with a focus on reactions to the antigenic hepatitis B surface antigen, including small, middle, and large surface antigens. This paper also reviews characteristics of the immune response to the hepatitis D antigen (including small and large antigens), the only protein expressed by hepatitis D. Lastly, we conclude with a discussion of recent therapeutic advances pertaining to these viruses.
Language	English
Publishing date	2022-12-15
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms232415973
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