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Article ; Online: Recent advances in antiviral drug development towards dengue virus.

Troost, Berit / Smit, Jolanda M

2020 Volume 43, Page(s) 9–21

Abstract: Despite the high disease burden of dengue virus, there is no approved antiviral treatment or broadly applicable vaccine to treat or prevent dengue virus infection. In the last decade, many antiviral compounds have been identified but only few have been ... ...

Abstract	Despite the high disease burden of dengue virus, there is no approved antiviral treatment or broadly applicable vaccine to treat or prevent dengue virus infection. In the last decade, many antiviral compounds have been identified but only few have been further evaluated in pre-clinical or clinical trials. This review will give an overview of the direct-acting and host-directed antivirals identified to date. Furthermore, important parameters for further development that is, drug properties including efficacy, specificity and stability, pre-clinical animal testing, and combinational drug therapy will be discussed.
MeSH term(s)	Animals ; Antiviral Agents/pharmacology ; Dengue/drug therapy ; Dengue/virology ; Dengue Virus/drug effects ; Dengue Virus/genetics ; Dengue Virus/physiology ; Drug Development/trends ; Humans
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2020-08-11
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2611378-8
ISSN	1879-6265 ; 1879-6257
ISSN (online)	1879-6265
ISSN	1879-6257
DOI	10.1016/j.coviro.2020.07.009
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Impact of COVID-19 containment measures on perceived health and health-protective behavior: a longitudinal study.

van Kersen, Warner / de Rooij, Myrna M T / Portengen, Lützen / Diez, Nekane Sandoval / Pieterson, Inka / Tewis, Marjan / Boer, Jolanda M A / Koppelman, Gerard / Vonk, Judith M / Vermeulen, Roel / Gehring, Ulrike / Huss, Anke / Smit, Lidwien A M

Scientific reports

2024 Volume 14, Issue 1, Page(s) 419

Abstract: This longitudinal study aimed to assess the impact of COVID-19 containment measures on perceived health, health protective behavior and risk perception, and investigate whether chronic disease status and urbanicity of the residential area modify these ... ...

Abstract	This longitudinal study aimed to assess the impact of COVID-19 containment measures on perceived health, health protective behavior and risk perception, and investigate whether chronic disease status and urbanicity of the residential area modify these effects. Participants (n = 5420) were followed for up to 14 months (September 2020-October 2021) by monthly questionnaires. Chronic disease status was obtained at baseline. Urbanicity of residential areas was assessed based on postal codes or neighborhoods. Exposure to containment measures was assessed using the Containment and Health Index (CHI). Bayesian multilevel-models were used to assess effect modification of chronic disease status and urbanicity by CHI. CHI was associated with higher odds for worse physical health in people with chronic disease (OR = 1.09, 95% credibility interval (CrI) = 1.01, 1.17), but not in those without (OR = 1.01, Crl = 0.95, 1.06). Similarly, the association of CHI with higher odds for worse mental health in urban dwellers (OR = 1.31, Crl = 1.23, 1.40) was less pronounced in rural residents (OR = 1.20, Crl = 1.13, 1.28). Associations with behavior and risk perception also differed between groups. Our study suggests that individuals with chronic disease and those living in urban areas are differentially affected by government measures put in place to manage the COVID-19 pandemic. This highlights the importance of considering vulnerable subgroups in decision making regarding containment measures.
MeSH term(s)	Humans ; COVID-19/epidemiology ; Longitudinal Studies ; Pandemics/prevention & control ; Bayes Theorem ; Health Status ; Chronic Disease
Language	English
Publishing date	2024-01-03
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/s41598-023-50542-1
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Article ; Online: Strategies employed by viruses to manipulate autophagy.

Dinesh Kumar, Nilima / Smit, Jolanda M / Reggiori, Fulvio

Progress in molecular biology and translational science

2020 Volume 172, Page(s) 203–237

Abstract: Autophagy, originally described as a conserved bulk degradation pathway important to maintain cellular homeostasis during starvation, has also been implicated in playing a central role in multiple physiological processes. For example, autophagy is part ... ...

Abstract	Autophagy, originally described as a conserved bulk degradation pathway important to maintain cellular homeostasis during starvation, has also been implicated in playing a central role in multiple physiological processes. For example, autophagy is part of our innate immunity by targeting intracellular pathogens to lysosomes for degradation in a process called xenophagy. Coevolution and adaptation between viruses and autophagy have armed viruses with a multitude of strategies to counteract the antiviral functions of the autophagy pathway. In addition, some viruses have acquired mechanisms to exploit specific functions of either autophagy or the key components of this process, the autophagy-related (ATG) proteins, to promote viral replication and pathogenesis. In this chapter, we describe several examples where the strategy employed by a virus to subvert autophagy has been described with molecular detail. Their stratagems positively or negatively target practically all the steps of autophagy, including the signaling pathways regulating this process. This highlights the intricate relationship between autophagy and viruses and how by commandeering autophagy, viruses have devised ways to fine-tune their replication.
Language	English
Publishing date	2020-02-10
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2471995-X
ISSN	1878-0814 ; 0079-6603 ; 1877-1173
ISSN (online)	1878-0814
ISSN	0079-6603 ; 1877-1173
DOI	10.1016/bs.pmbts.2020.01.004
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Article ; Online: Colocalization of Chikungunya Virus with Its Receptor MXRA8 during Cell Attachment, Internalization, and Membrane Fusion.

Feng, Fei / Bouma, Ellen M / Hu, Gaowei / Zhu, Yunkai / Yu, Yin / Smit, Jolanda M / Diamond, Michael S / Zhang, Rong

Journal of virology

2023 Volume 97, Issue 5, Page(s) e0155722

Abstract: Arthritogenic alphaviruses, including chikungunya virus (CHIKV), preferentially target joint tissues and cause chronic rheumatic disease that adversely impacts the quality of life of patients. Viruses enter target cells via interaction with cell surface ... ...

Abstract	Arthritogenic alphaviruses, including chikungunya virus (CHIKV), preferentially target joint tissues and cause chronic rheumatic disease that adversely impacts the quality of life of patients. Viruses enter target cells via interaction with cell surface receptor(s), which determine the viral tissue tropism and pathogenesis. Although MXRA8 is a recently identified receptor for several clinically relevant arthritogenic alphaviruses, its detailed role in the cell entry process has not been fully explored. We found that in addition to its localization on the plasma membrane, MXRA8 is present in acidic organelles, endosomes, and lysosomes. Moreover, MXRA8 is internalized into cells without a requirement for its transmembrane and cytoplasmic domains. Confocal microscopy and live cell imaging revealed that MXRA8 interacts with CHIKV at the cell surface and then enters cells along with CHIKV particles. At the moment of membrane fusion in the endosomes, many viral particles are still colocalized with MXRA8. These findings provide insight as to how MXRA8 functions in alphavirus internalization and suggest possible targets for antiviral development.
MeSH term(s)	Humans ; Chikungunya virus/physiology ; Virus Internalization ; Membrane Fusion ; Quality of Life ; Chikungunya Fever ; Rheumatic Diseases
Language	English
Publishing date	2023-05-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/jvi.01557-22
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Article ; Online: Visualization of conformational changes and membrane remodeling leading to genome delivery by viral class-II fusion machinery.

Mangala Prasad, Vidya / Blijleven, Jelle S / Smit, Jolanda M / Lee, Kelly K

Nature communications

2022 Volume 13, Issue 1, Page(s) 4772

Abstract: Chikungunya virus (CHIKV) is a human pathogen that delivers its genome to the host cell cytoplasm through endocytic low pH-activated membrane fusion mediated by class-II fusion proteins. Though structures of prefusion, icosahedral CHIKV are available, ... ...

Abstract	Chikungunya virus (CHIKV) is a human pathogen that delivers its genome to the host cell cytoplasm through endocytic low pH-activated membrane fusion mediated by class-II fusion proteins. Though structures of prefusion, icosahedral CHIKV are available, structural characterization of virion interaction with membranes has been limited. Here, we have used cryo-electron tomography to visualize CHIKV's complete membrane fusion pathway, identifying key intermediary glycoprotein conformations coupled to membrane remodeling events. Using sub-tomogram averaging, we elucidate features of the low pH-exposed virion, nucleocapsid and full-length E1-glycoprotein's post-fusion structure. Contrary to class-I fusion systems, CHIKV achieves membrane apposition by protrusion of extended E1-glycoprotein homotrimers into the target membrane. The fusion process also features a large hemifusion diaphragm that transitions to a wide pore for intact nucleocapsid delivery. Our analyses provide comprehensive ultrastructural insights into the class-II virus fusion system function and direct mechanistic characterization of the fundamental process of protein-mediated membrane fusion.
MeSH term(s)	Chikungunya virus/genetics ; Glycoproteins/analysis ; Humans ; Membrane Fusion ; Viral Envelope Proteins/chemistry ; Viral Envelope Proteins/genetics ; Viral Fusion Proteins/chemistry ; Viral Fusion Proteins/genetics ; Virion/metabolism ; Virus Internalization
Chemical Substances	Glycoproteins ; Viral Envelope Proteins ; Viral Fusion Proteins
Language	English
Publishing date	2022-08-15
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-32431-9
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Article ; Online: Vitamin D-induced LL-37 modulates innate immune responses of human primary macrophages during DENV-2 infection.

Castillo, Jorge Andrés / Giraldo, Diana Marcela / Smit, Jolanda M / Rodenhuis-Zybert, Izabela A / Urcuqui-Inchima, Silvio

Pathogens and disease

2022 Volume 80, Issue 1

Abstract: Epidemics of dengue, an acute and potentially severe disease caused by mosquito-borne dengue virus (DENV), pose a major challenge to clinicians and health care services across the sub(tropics). Severe disease onset is associated with a dysregulated ... ...

Abstract	Epidemics of dengue, an acute and potentially severe disease caused by mosquito-borne dengue virus (DENV), pose a major challenge to clinicians and health care services across the sub(tropics). Severe disease onset is associated with a dysregulated inflammatory response to the virus, and there are currently no drugs to alleviate disease symptoms. LL-37 is a potent antimicrobial peptide with a wide range of immunoregulatory properties. In this study, we assessed the effect of LL-37 on DENV-2-induced responses in human monocyte-derived macrophages (MDMs). We show that simultaneous exposure of exogenous LL-37 and DENV-2 resulted in reduced replication of the virus in MDMs, while the addition of LL-37 postexposure to DENV-2 did not. Interestingly, the latter condition reduced the production of IL-6 and increased the expression of genes involved in virus sensing and antiviral response. Finally, we demonstrate that low endogenous levels and limited production of LL-37 in MDMs in response to DENV-2 infection can be increased by differentiating MDMs in the presence of Vitamin D (VitD3). Taken together, this study demonstrates that in addition to its antimicrobial properties, LL-37 has immunomodulatory properties in the curse of DENV infection and its production can be increased by VitD3.
MeSH term(s)	Animals ; Dengue ; Dengue Virus ; Humans ; Immunity, Innate ; Macrophages ; Virus Replication ; Vitamin D/metabolism ; Vitamin D/pharmacology
Chemical Substances	Vitamin D (1406-16-2)
Language	English
Publishing date	2022-05-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2049-632X
ISSN (online)	2049-632X
DOI	10.1093/femspd/ftac014
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Article: Characterization of soluble TLR2 and CD14 levels during acute dengue virus infection.

Upasani, Vinit / Ter Ellen, Bram M / Sann, Sotheary / Lay, Sokchea / Heng, Sothy / Laurent, Denis / Ly, Sowath / Duong, Veasna / Dussart, Philippe / Smit, Jolanda M / Cantaert, Tineke / Rodenhuis-Zybert, Izabela A

Heliyon

2023 Volume 9, Issue 6, Page(s) e17265

Abstract: Dengue virus infection results in a broad spectrum of diseases ranging from mild dengue fever (DF) to severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Hitherto, there is no consensus biomarker for the prediction of severe dengue ... ...

Abstract	Dengue virus infection results in a broad spectrum of diseases ranging from mild dengue fever (DF) to severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Hitherto, there is no consensus biomarker for the prediction of severe dengue disease in patients. Yet, early identification of patients who progress to severe dengue is pivotal for better clinical management. We have recently reported that an increased frequency of classical (CD14
Language	English
Publishing date	2023-06-21
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2023.e17265
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Article ; Online: Role of autophagy during the replication and pathogenesis of common mosquito-borne flavi- and alphaviruses.

Echavarria-Consuegra, Liliana / Smit, Jolanda M / Reggiori, Fulvio

Open biology

2019 Volume 9, Issue 3, Page(s) 190009

Abstract: Arboviruses that are transmitted to humans by mosquitoes represent one of the most important causes of febrile illness worldwide. In recent decades, we have witnessed a dramatic re-emergence of several mosquito-borne arboviruses, including dengue virus ( ... ...

Abstract	Arboviruses that are transmitted to humans by mosquitoes represent one of the most important causes of febrile illness worldwide. In recent decades, we have witnessed a dramatic re-emergence of several mosquito-borne arboviruses, including dengue virus (DENV), West Nile virus (WNV), chikungunya virus (CHIKV) and Zika virus (ZIKV). DENV is currently the most common mosquito-borne arbovirus, with an estimated 390 million infections worldwide annually. Despite a global effort, no specific therapeutic strategies are available to combat the diseases caused by these viruses. Multiple cellular pathways modulate the outcome of infection by either promoting or hampering viral replication and/or pathogenesis, and autophagy appears to be one of them. Autophagy is a degradative pathway generally induced to counteract viral infection. Viruses, however, have evolved strategies to subvert this pathway and to hijack autophagy components for their own benefit. In this review, we will focus on the role of autophagy in mosquito-borne arboviruses with emphasis on DENV, CHIKV, WNV and ZIKV, due to their epidemiological importance and high disease burden.
MeSH term(s)	Alphavirus/physiology ; Animals ; Autophagy/physiology ; Culicidae/virology ; Flavivirus/physiology ; Host-Pathogen Interactions ; Humans ; Mosquito Vectors/virology ; RNA Virus Infections/physiopathology ; RNA Virus Infections/virology ; Virus Replication/physiology
Language	English
Publishing date	2019-03-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2630944-0
ISSN	2046-2441 ; 2046-2441
ISSN (online)	2046-2441
ISSN	2046-2441
DOI	10.1098/rsob.190009
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Article ; Online: Impact of COVID-19 containment measures on perceived health and health-protective behavior

Warner van Kersen / Myrna M. T. de Rooij / Lützen Portengen / Nekane Sandoval Diez / Inka Pieterson / Marjan Tewis / Jolanda M. A. Boer / Gerard Koppelman / Judith M. Vonk / Roel Vermeulen / Ulrike Gehring / Anke Huss / Lidwien A. M. Smit

Scientific Reports, Vol 14, Iss 1, Pp 1-

a longitudinal study

2024 Volume 9

Abstract: Abstract This longitudinal study aimed to assess the impact of COVID-19 containment measures on perceived health, health protective behavior and risk perception, and investigate whether chronic disease status and urbanicity of the residential area modify ...

Abstract	Abstract This longitudinal study aimed to assess the impact of COVID-19 containment measures on perceived health, health protective behavior and risk perception, and investigate whether chronic disease status and urbanicity of the residential area modify these effects. Participants (n = 5420) were followed for up to 14 months (September 2020-October 2021) by monthly questionnaires. Chronic disease status was obtained at baseline. Urbanicity of residential areas was assessed based on postal codes or neighborhoods. Exposure to containment measures was assessed using the Containment and Health Index (CHI). Bayesian multilevel-models were used to assess effect modification of chronic disease status and urbanicity by CHI. CHI was associated with higher odds for worse physical health in people with chronic disease (OR = 1.09, 95% credibility interval (CrI) = 1.01, 1.17), but not in those without (OR = 1.01, Crl = 0.95, 1.06). Similarly, the association of CHI with higher odds for worse mental health in urban dwellers (OR = 1.31, Crl = 1.23, 1.40) was less pronounced in rural residents (OR = 1.20, Crl = 1.13, 1.28). Associations with behavior and risk perception also differed between groups. Our study suggests that individuals with chronic disease and those living in urban areas are differentially affected by government measures put in place to manage the COVID-19 pandemic. This highlights the importance of considering vulnerable subgroups in decision making regarding containment measures.
Keywords	Medicine ; R ; Science ; Q
Subject code	360
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Novel high-yield potato protease inhibitor panels block a wide array of proteases involved in viral infection and crucial tissue damage.

Visser, Nienke / Herreman, Laure C M / Vandooren, Jennifer / Pereira, Rafaela Vaz Sousa / Opdenakker, Ghislain / Spelbrink, Robin E J / Wilbrink, Maarten H / Bremer, Edwin / Gosens, Reinoud / Nawijn, Martijn C / van der Ende-Metselaar, Heidi H / Smit, Jolanda M / Laus, Marc C / Laman, Jon D

Journal of molecular medicine (Berlin, Germany)

2024 Volume 102, Issue 4, Page(s) 521–536

Abstract: Viruses critically rely on various proteases to ensure host cell entry and replication. In response to viral infection, the host will induce acute tissue inflammation pulled by granulocytes. Upon hyperactivation, neutrophil granulocytes may cause undue ... ...

Abstract	Viruses critically rely on various proteases to ensure host cell entry and replication. In response to viral infection, the host will induce acute tissue inflammation pulled by granulocytes. Upon hyperactivation, neutrophil granulocytes may cause undue tissue damage through proteolytic degradation of the extracellular matrix. Here, we assess the potential of protease inhibitors (PI) derived from potatoes in inhibiting viral infection and reducing tissue damage. The original full spectrum of potato PI was developed into five fractions by means of chromatography and hydrolysis. Individual fractions showed varying inhibitory efficacy towards a panel of proteases including trypsin, chymotrypsin, ACE2, elastase, and cathepsins B and L. The fractions did not interfere with SARS-CoV-2 infection of Vero E6 cells in vitro. Importantly, two of the fractions fully inhibited elastin-degrading activity of complete primary human neutrophil degranulate. These data warrant further development of potato PI fractions for biomedical purposes, including tissue damage crucial to SARS-CoV-2 pathogenesis. KEY MESSAGES: Protease inhibitor fractions from potato differentially inhibit a series of human proteases involved in viral replication and in tissue damage by overshoot inflammation. Protease inhibition of cell surface receptors such as ACE2 does not prevent virus infection of Vero cells in vitro. Protease inhibitors derived from potato can fully inhibit elastin-degrading primary human neutrophil proteases. Protease inhibitor fractions can be produced at high scale (hundreds of thousands of kilograms, i.e., tons) allowing economically feasible application in lower and higher income countries.
MeSH term(s)	Animals ; Chlorocebus aethiops ; Humans ; Solanum tuberosum/metabolism ; Peptide Hydrolases ; Vero Cells ; Angiotensin-Converting Enzyme 2 ; Protease Inhibitors/pharmacology ; Protease Inhibitors/metabolism ; Enzyme Inhibitors ; Inflammation ; Antiviral Agents ; COVID-19 ; Elastin/metabolism
Chemical Substances	Peptide Hydrolases (EC 3.4.-) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Protease Inhibitors ; Enzyme Inhibitors ; Antiviral Agents ; Elastin (9007-58-3)
Language	English
Publishing date	2024-02-21
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1223802-8
ISSN	1432-1440 ; 0946-2716
ISSN (online)	1432-1440
ISSN	0946-2716
DOI	10.1007/s00109-024-02423-x
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