Molecular Simulations Reveal the Role of Antibody Fine Specificity and Viral Maturation State on Antibody-Dependent Enhancement of Infection in Dengue Virus

<b><i>Background:</i></b> Antibody-dependent enhancement (ADE) of dengue virus (DENV) infection is identified as the main risk factor of severe dengue diseases. The underlying mechanisms leading to severe dengue fever remain unclear. <b><i>Methods:</i></b> THP-1 cells were treated with an autophagy inducer (rapamycin) or inhibitor (3-methyladenine [3-MA]) and infected with DENV and DENV-ADE. In order to investigate the expression profile of autophagy-related genes in DENV-ADE and DENV direct infection of THP-1 cells, the PCR array including 84 autophagy-related genes was selected to detect the expression of related genes, and then heat map and clustergram were established by analysis software to compare the expression differences of these genes between the DENV-ADE and DENV direct infection. <b><i>Results:</i></b> Autophagy-inducing complex related genes ATG5 and ATG12 were upregulated, and autophagosomes were also observed by transmission electron microscopy among DENV-ADE- and DENV-infected THP-1 cells, which indicated that autophagy was involved in dengue infection. The results show that 3-MA has a significant inhibitory effect on ATG12 in THP-1 cells; on the contrary, the expression of ATG12 was upregulated in THP-1 cells that were treated with rapamycin. The autophagy-related genes ESR1, INS, BNIP3, FAS, TGM2, ATG9B, and DAPK1 exhibited significant differences between DENV-ADE and DENV direct infection groups. <b><i>Conclusion:</i></b> In the present study, an additional mechanism of autophagy was inhibited by the autophagy inhibitor (3-MA) in DENV- and DENV-ADE-infected THP-1 cells. Our finding provided a clear link between autophagy and antibody-enhanced infection of DENV.

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Antibody-dependent enhancement of virus infection and disease: implications in COVID-19

Journal of Basic and Clinical Physiology and Pharmacology ◽

10.1515/jbcpp-2021-0264 ◽

2022 ◽

Vol 0 (0) ◽

Author(s):

Ajay Kumar Shukla ◽

Saurav Misra

Keyword(s):

Virus Infection ◽

Severe Acute Respiratory Syndrome ◽

Dengue Virus ◽

Viral Infection ◽

Vaccine Development ◽

Antibody Treatment ◽

Antibody Dependent Enhancement ◽

Rapid Spread ◽

Clinical Consequences

Abstract Antibody-dependent enhancement (ADE) can be seen in a variety of viruses. It has a deleterious impact on antibody treatment of viral infection. This effect was first discovered in the dengue virus, and it has since been discovered in the coronavirus. Over 213 million people have been affected by the rapid spread of the newly emerging coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19). The new coronavirus offers a significant threat and has sparked widespread concern. ADE in dengue virus and other viruses are discussed with possible effect on COVID-19 treatment and vaccine development will need to consider this phenomenon to ensure it is mitigated and avoided altogether. In these case scenarios, the role of ADE and its clinical consequences remains to be explored for this newly detected virus.

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On the Use of Quantum Thermal Bath in Unimolecular Fragmentation Simulations

10.26434/chemrxiv.8870594.v2 ◽

2019 ◽

Author(s):

Riccardo Spezia ◽

Hichem Dammak

Keyword(s):

Degrees Of Freedom ◽

Molecular Simulations ◽

Zero Point ◽

Thermal Bath ◽

Unimolecular Dissociation ◽

Point Energy ◽

Rotational Degrees Of Freedom ◽

The Difference ◽

Nuclear Effects

<div> <div> <div> <p>In the present work we have investigated the possibility of using the Quantum Thermal Bath (QTB) method in molecular simulations of unimolecular dissociation processes. Notably, QTB is aimed in introducing quantum nuclear effects with a com- putational time which is basically the same as in newtonian simulations. At this end we have considered the model fragmentation of CH4 for which an analytical function is present in the literature. Moreover, based on the same model a microcanonical algorithm which monitor zero-point energy of products, and eventually modifies tra- jectories, was recently proposed. We have thus compared classical and quantum rate constant with these different models. QTB seems to correctly reproduce some quantum features, in particular the difference between classical and quantum activation energies, making it a promising method to study unimolecular fragmentation of much complex systems with molecular simulations. The role of QTB thermostat on rotational degrees of freedom is also analyzed and discussed. </p> </div> </div> </div>

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Faculty Opinions recommendation of Dengue virus (DENV) antibody-dependent enhancement of infection upregulates the production of anti-inflammatory cytokines, but suppresses anti-DENV free radical and pro-inflammatory cytokine production, in THP-1 cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1090961.544319 ◽

2007 ◽

Author(s):

Scott Halstead

Keyword(s):

Free Radical ◽

Dengue Virus ◽

Inflammatory Cytokines ◽

Inflammatory Cytokine ◽

Cytokine Production ◽

Inflammatory Cytokine Production ◽

Antibody Dependent Enhancement ◽

Anti Inflammatory

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Structural perspectives of antibody-dependent enhancement of infection of dengue virus

Current Opinion in Virology ◽

10.1016/j.coviro.2019.02.002 ◽

2019 ◽

Vol 36 ◽

pp. 1-8 ◽

Cited By ~ 7

Author(s):

Seamus R Morrone ◽

Shee-Mei Lok

Keyword(s):

Dengue Virus ◽

Antibody Dependent Enhancement

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Exploring secondary interactions and the role of temperature in moisture-contaminated polymer networks through molecular simulations

Soft Matter ◽

10.1039/d0sm02009e ◽

2021 ◽

Vol 17 (10) ◽

pp. 2942-2956

Author(s):

Rishabh D. Guha ◽

Ogheneovo Idolor ◽

Katherine Berkowitz ◽

Melissa Pasquinelli ◽

Landon R. Grace

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulations ◽

Temperature Variation ◽

Polymer Networks ◽

Molecular Simulations ◽

Effect Of Temperature ◽

Secondary Interactions ◽

Dynamics Simulations ◽

Secondary Bonding

We investigated the effect of temperature variation on the secondary bonding interactions between absorbed moisture and epoxies with different morphologies using molecular dynamics simulations.

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Antiviral Role of Phenolic Compounds against Dengue Virus: A Review

Biomolecules ◽

10.3390/biom11010011 ◽

2020 ◽

Vol 11 (1) ◽

pp. 11

Author(s):

Vanessa Loaiza-Cano ◽

Laura Milena Monsalve-Escudero ◽

Carlos da Silva Maia Bezerra Filho ◽

Marlen Martinez-Gutierrez ◽

Damião Pergentino de Sousa

Keyword(s):

Phenolic Compounds ◽

Dengue Virus ◽

Biological Activities ◽

Antiviral Effect ◽

Health Concern ◽

Host Proteins ◽

Viral Particles ◽

Antiviral Role ◽

Productive Replication

Phenolic compounds have been related to multiple biological activities, and the antiviral effect of these compounds has been demonstrated in several viral models of public health concern. In this review, we show the antiviral role of phenolic compounds against dengue virus (DENV), the most widespread arbovirus globally that, after its re-emergence, has caused multiple epidemic outbreaks, especially in the last two years. Twenty phenolic compounds with anti-DENV activity are discussed, including the multiple mechanisms of action, such as those directed against viral particles or viral proteins, host proteins or pathways related to the productive replication viral cycle and the spread of the infection.

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