scholarly journals Generation of Spike-Extracellular Vesicles (S-EVs) as a Tool to Mimic SARS-CoV-2 Interaction with Host Cells

Cells ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 146
Author(s):  
Roberta Verta ◽  
Cristina Grange ◽  
Renata Skovronova ◽  
Adele Tanzi ◽  
Licia Peruzzi ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Size Structure ◽  
Super Resolution ◽  
Host Cells ◽  
Spike Protein ◽  
Vector Coding ◽  
Therapeutic Drugs ◽  
Pre Treatment ◽  
Host Virus Interactions ◽  
Virus Interactions

Extracellular vesicles (EVs) and viruses share common features: size, structure, biogenesis and uptake. In order to generate EVs expressing the SARS-CoV-2 spike protein on their surface (S-EVs), we collected EVs from SARS-CoV-2 spike expressing human embryonic kidney (HEK-293T) cells by stable transfection with a vector coding for the S1 and S2 subunits. S-EVs were characterized using nanoparticle tracking analysis, ExoView and super-resolution microscopy. We obtained a population of EVs of 50 to 200 nm in size. Spike expressing EVs represented around 40% of the total EV population and co-expressed spike protein with tetraspanins on the surfaces of EVs. We subsequently used ACE2-positive endothelial and bronchial epithelial cells for assessing the internalization of labeled S-EVs using a cytofluorimetric analysis. Internalization of S-EVs was higher than that of control EVs from non-transfected cells. Moreover, S-EV uptake was significantly decreased by anti-ACE2 antibody pre-treatment. Furthermore, colchicine, a drug currently used in clinical trials, significantly reduced S-EV entry into the cells. S-EVs represent a simple, safe, and scalable model to study host-virus interactions and the mechanisms of novel therapeutic drugs.

scholarly journals Repurposing Therapeutics for COVID-19: Supercomputer-Based Docking to the SARS-CoV-2 Viral Spike Protein and Viral Spike Protein-Human ACE2 Interface

2020 ◽  
Author(s):  
Micholas Smith ◽  
Jeremy C. Smith
Keyword(s):  
Small Molecules ◽  
High Throughput Screening ◽  
Protein S ◽  
Host Cells ◽  
Spike Protein ◽  
The Novel ◽  
S Protein ◽  
Host Virus Interactions ◽  
Virus Interactions ◽  
Ranked List

The novel Wuhan coronavirus (SARS-CoV-2) has been sequenced, and the virus shares substantial similarity with SARS-CoV. Here, using a computational model of the spike protein (S-protein) of SARS-CoV-2 interacting with the human ACE2 receptor, we make use of the world's most powerful supercomputer, SUMMIT, to enact an ensemble docking virtual high-throughput screening campaign and identify small-molecules which bind to either the isolated Viral S-protein at its host receptor region or to the S protein-human ACE2 interface. We hypothesize the identified small-molecules may be repurposed to limit viral recognition of host cells and/or disrupt host-virus interactions. A ranked list of compounds is given that can be tested experimentally.<br>

scholarly journals Repurposing Therapeutics for COVID-19: Supercomputer-Based Docking to the SARS-CoV-2 Viral Spike Protein and Viral Spike Protein-Human ACE2 Interface

2020 ◽  
Author(s):  
Micholas Smith ◽  
Jeremy C. Smith
Keyword(s):  
Small Molecules ◽  
High Throughput Screening ◽  
Protein S ◽  
Host Cells ◽  
Spike Protein ◽  
The Novel ◽  
S Protein ◽  
Host Virus Interactions ◽  
Virus Interactions ◽  
Ranked List

The novel Wuhan coronavirus (SARS-CoV-2) has been sequenced, and the virus shares substantial similarity with SARS-CoV. Here, using a computational model of the spike protein (S-protein) of SARS-CoV-2 interacting with the human ACE2 receptor, we make use of the world's most powerful supercomputer, SUMMIT, to enact an ensemble docking virtual high-throughput screening campaign and identify small-molecules which bind to either the isolated Viral S-protein at its host receptor region or to the S protein-human ACE2 interface. We hypothesize the identified small-molecules may be repurposed to limit viral recognition of host cells and/or disrupt host-virus interactions. A ranked list of compounds is given that can be tested experimentally.<br>

scholarly journals Repurposing Therapeutics for COVID-19: Supercomputer-Based Docking to the SARS-CoV-2 Viral Spike Protein and Viral Spike Protein-Human ACE2 Interface

2020 ◽  
Author(s):  
Micholas Smith ◽  
Jeremy C. Smith
Keyword(s):  
Small Molecules ◽  
High Throughput Screening ◽  
Protein S ◽  
Host Cells ◽  
Spike Protein ◽  
The Novel ◽  
S Protein ◽  
Host Virus Interactions ◽  
Virus Interactions ◽  
Ranked List

The novel Wuhan coronavirus (SARS-CoV-2) has been sequenced, and the virus shares substantial similarity with SARS-CoV. Here, using a computational model of the spike protein (S-protein) of SARS-CoV-2 interacting with the human ACE2 receptor, we make use of the world's most powerful supercomputer, SUMMIT, to enact an ensemble docking virtual high-throughput screening campaign and identify small-molecules which bind to either the isolated Viral S-protein at its host receptor region or to the S protein-human ACE2 interface. We hypothesize the identified small-molecules may be repurposed to limit viral recognition of host cells and/or disrupt host-virus interactions. A ranked list of compounds is given that can be tested experimentally.<br>

scholarly journals Repurposing Therapeutics for COVID-19: Supercomputer-Based Docking to the SARS-CoV-2 Viral Spike Protein and Viral Spike Protein-Human ACE2 Interface

2020 ◽  
Author(s):  
Micholas Smith ◽  
Jeremy C. Smith
Keyword(s):  
Small Molecules ◽  
High Throughput Screening ◽  
Protein S ◽  
Host Cells ◽  
Spike Protein ◽  
The Novel ◽  
S Protein ◽  
Host Virus Interactions ◽  
Virus Interactions ◽  
Ranked List

The novel Wuhan coronavirus (SARS-CoV-2) has been sequenced, and the virus shares substantial similarity with SARS-CoV. Here, using a computational model of the spike protein (S-protein) of SARS-CoV-2 interacting with the human ACE2 receptor, we make use of the world's most powerful supercomputer, SUMMIT, to enact an ensemble docking virtual high-throughput screening campaign and identify small-molecules which bind to either the isolated Viral S-protein at its host receptor region or to the S protein-human ACE2 interface. We hypothesize the identified small-molecules may be repurposed to limit viral recognition of host cells and/or disrupt host-virus interactions. A ranked list of compounds is given that can be tested experimentally.<br>

scholarly journals CHEMICAL STUDIES IN HOST-VIRUS INTERACTIONS

1948 ◽  
Vol 87 (4) ◽  
pp. 259-274 ◽  
Author(s):  
Catherine B. Fowler ◽  
Seymour S. Cohen
Keyword(s):  
Amino Acids ◽  
Burst Size ◽  
Host Cells ◽  
Simple Medium ◽  
Chemical Studies ◽  
One Step ◽  
Nutritional Environment ◽  
The One ◽  
Host Virus Interactions ◽  
Virus Interactions

Using the one-step growth technique the production of the virus T2 in its host, measured by latent period and burst size, was shown to depend on the nutritional environment of the host cell. When E. coli, grown in broth, was transferred to a simple medium, single organic compounds such as some amino acids and nucleosides were found to increase or accelerate the synthesis of virus. An antimetabolite of glutamic acid, an amino acid important for virus synthesis, was shown to be inhibitory. Several naturally occurring amino acids, leucine, serine, and cysteine, inhibited virus synthesis in the simple medium. A chemically defined mixture was found which supported a rate of virus synthesis very nearly comparable to that found for host cells in nutrient broth.

In Search for Effective and Safe Drugs Against SARS-CoV-2: Part I] Simulated Interactions Between Selected Nutraceuticals, ACE2 Enzyme and S Protein Simple Peptide Sequences

2020 ◽  
Author(s):  
M. Sabry Abdel-Mottaleb ◽  
Yousra Abdel-Mottaleb
Keyword(s):  
Treatment Options ◽  
Minimum Energy ◽  
Drug Binding ◽  
Host Cells ◽  
S Protein ◽  
Drug Molecules ◽  
Binding Interface ◽  
Natural Drugs ◽  
Host Virus Interactions ◽  
Virus Interactions

Coronavirus disease (COVID-19) remains a world pandemic with little treatment options. Nature has provided a plethora of compounds that may offer potential protection and/or treatment choices. Earlier studies have shown a pivotal role of Angiotensin converting enzyme 2 (ACE2) in the pathogenesis of COVID-19. In this context, seven natural compounds were selected and their binding to specific peptide sequences of the coronavirus S-protein: ACE2 interface-drug binding adduct were calculated. Further to the natural drugs, we also similarly examined four well-known antiviral drugs. Moreover, the binding-interface of the isolated coronavirus S-protein and the isolated ACE2 receptor were also individually explored. The identified drug molecules positioned itself achieving geometries of minimum energy resulting in limiting viral recognition of host cells or to disturb host-virus interactions. The frontier orbitals (HOMO-LUMO) play crucial role in the binding interactions of the studied molecules. Most of the drugs act as electron sink whereas the S protein behaves as nucleophile. The results reported pave the way for the identification of small-drug molecule of natural origin with potentially tolerable side effects that can offer protection and/or treatment against coronavirus S-protein COVID-19. Experimental validation is of urgent demand.<br>

scholarly journals Genome-Wide Gene Expression Analysis Identifies the Proto-oncogene Tyrosine-Protein Kinase Src as a Crucial Virulence Determinant of Infectious Laryngotracheitis Virus in Chicken Cells

2015 ◽  
Vol 90 (1) ◽  
pp. 9-21 ◽  
Author(s):  
Hai Li ◽  
Fengjie Wang ◽  
Zongxi Han ◽  
Qi Gao ◽  
Huixin Li ◽  
...  
Keyword(s):  
Cell Death ◽  
Protein Kinase ◽  
Host Cells ◽  
In Ovo ◽  
Promising Strategy ◽  
Genome Wide ◽  
Infectious Laryngotracheitis ◽  
Tyrosine Protein Kinase ◽  
Host Virus Interactions ◽  
Virus Interactions

ABSTRACT Given the side effects of vaccination against infectious laryngotracheitis (ILT), novel strategies for ILT control and therapy are urgently needed. The modulation of host-virus interactions is a promising strategy to combat the virus; however, the interactions between the host and avian ILT herpesvirus (ILTV) are unclear. Using genome-wide transcriptome studies in combination with a bioinformatic analysis, we identified proto-oncogene tyrosine-protein kinase Src (Src) to be an important modulator of ILTV infection. Src controls the virulence of ILTV and is phosphorylated upon ILTV infection. Functional studies revealed that Src prolongs the survival of host cells by increasing the threshold of virus-induced cell death. Therefore, Src is essential for viral replication in vitro and in ovo but is not required for ILTV-induced cell death. Furthermore, our results identify a positive-feedback loop between Src and the tyrosine kinase focal adhesion kinase (FAK), which is necessary for the phosphorylation of either Src or FAK and is required for Src to modulate ILTV infection. To the best of our knowledge, we are the first to identify a key host regulator controlling host-ILTV interactions. We believe that our findings have revealed a new potential therapeutic target for ILT control and therapy. IMPORTANCE Despite the extensive administration of live attenuated vaccines starting from the mid-20th century and the administration of recombinant vaccines in recent years, infectious laryngotracheitis (ILT) outbreaks due to avian ILT herpesvirus (ILTV) occur worldwide annually. Presently, there are no drugs or control strategies that effectively treat ILT. Targeting of host-virus interactions is considered to be a promising strategy for controlling ILTV infections. However, little is known about the mechanisms governing host-ILTV interactions. The results from our study advance our understanding of host-ILTV interactions on a molecular level and provide experimental evidence that it is possible to control ILT via the manipulation of host-virus interactions.

scholarly journals Repurposing Therapeutics for the Wuhan Coronavirus nCov-2019: Supercomputer-Based Docking to the Viral S Protein and Human ACE2 Interface

2020 ◽  
Author(s):  
Micholas Smith ◽  
Jeremy C. Smith
Keyword(s):  
Small Molecules ◽  
High Throughput Screening ◽  
Protein S ◽  
Spike Protein ◽  
The Novel ◽  
S Protein ◽  
Ensemble Docking ◽  
Host Virus Interactions ◽  
Virus Interactions ◽  
Ranked List

The novel Wuhan coronavirus (nCov-2019) has been sequenced, and the virus shares substantial similarity with SARS-CoV. Here, using a computational model of the spike protein (S-protein) nCov-2019 interacting with the human ACE2 receptor, we make use of the world's most powerful supercomputer, SUMMIT, to enact an ensemble docking virtual high-throughput screening campaign and identify small-molecules which may be repurposed to disrupt host-virus interactions. A ranked list of compounds is given that can be tested experimentally.<br>

scholarly journals Strategies and mechanisms of resistance to viruses in photosynthetic aquatic microorganisms

2012 ◽  
Vol 3 (1) ◽  
pp. 1 ◽  
Author(s):  
Rozenn Thomas ◽  
Stéphan Jacquet ◽  
Nigel Grimsley ◽  
Hervé Moreau
Keyword(s):  
Host Cells ◽  
Future Research ◽  
Aquatic Microorganisms ◽  
Photosynthetic Microorganisms ◽  
Host Virus Interactions ◽  
The Cost ◽  
Virus Interactions ◽  
Defence Strategies ◽  
Evolutionary Consequences ◽  
Resistance To Viruses

Surviving viral attack is essential for any species to avoid its irreversible removal from the ecosystem, and microbes must involve the resistance or susceptibility of individual cells. The co-existence between viruses and their hosts has led to the evolution of complex viral attack and host defence strategies. We review the state of the art about our understanding of resistance to viruses in aquatic eukaryotic photosynthetic microorganisms for which no synthesis has been provided yet, with comparisons to what is known for (cyano)bacteria or archaea. We discuss the cost of viral resistance to host cells, pointing out why it is important to consider its effect in studies of aquatic ecosystems, and how this may lead to a better understanding of population growth, structure, succession and blooms. The evolutionary consequences of resistance in the host-virus interactions are then reviewed, before considering possible perspectives for future research.

scholarly journals In Search for Effective and Safe Drugs Against SARS-CoV-2: Part I] Simulated Interactions Between Selected Nutraceuticals, ACE2 Enzyme and S Protein Simple Peptide Sequences

2020 ◽  
Author(s):  
M. Sabry Abdel-Mottaleb ◽  
Yousra Abdel-Mottaleb
Keyword(s):  
Treatment Options ◽  
Minimum Energy ◽  
Drug Binding ◽  
Host Cells ◽  
S Protein ◽  
Drug Molecules ◽  
Binding Interface ◽  
Natural Drugs ◽  
Host Virus Interactions ◽  
Virus Interactions

Coronavirus disease (COVID-19) remains a world pandemic with little treatment options. Nature has provided a plethora of compounds that may offer potential protection and/or treatment choices. Earlier studies have shown a pivotal role of Angiotensin converting enzyme 2 (ACE2) in the pathogenesis of COVID-19. In this context, seven natural compounds were selected and their binding to specific peptide sequences of the coronavirus S-protein: ACE2 interface-drug binding adduct were calculated. Further to the natural drugs, we also similarly examined four well-known antiviral drugs. Moreover, the binding-interface of the isolated coronavirus S-protein and the isolated ACE2 receptor were also individually explored. The identified drug molecules positioned itself achieving geometries of minimum energy resulting in limiting viral recognition of host cells or to disturb host-virus interactions. The frontier orbitals (HOMO-LUMO) play crucial role in the binding interactions of the studied molecules. Most of the drugs act as electron sink whereas the S protein behaves as nucleophile. The results reported pave the way for the identification of small-drug molecule of natural origin with potentially tolerable side effects that can offer protection and/or treatment against coronavirus S-protein COVID-19. Experimental validation is of urgent demand.<br>

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