scholarly journals Nanotechnology-Enabled COVID-19 mRNA Vaccines

Encyclopedia ◽  
2021 ◽  
Vol 1 (3) ◽  
pp. 773-780
Author(s):  
Yu Gao ◽  
Kaiyun Yang ◽  
Andrew N. Shelling ◽  
Zimei Wu
Keyword(s):  
Intracellular Delivery ◽  
Lipid Nanoparticles ◽  
Host Cells ◽  
Specific Antigens ◽  
Synthetic Mrna ◽  
Spike Proteins

COVID-19 mRNA vaccines contain synthetic mRNA sequences encoded for the Spike proteins expressed on the surface of SARS-CoV-2, and utilize the host cells to produce specific antigens that stimulate both humoral and cellular immunities. Lipid nanoparticles are essential to facilitate the intracellular delivery of the mRNA to its action site, the ribosome, to fully exert its effect.

scholarly journals Leveraging Deep Learning to Simulate Coronavirus Spike proteins has the potential to predict future Zoonotic sequences

2020 ◽  
Author(s):  
Lisa C Crossman
Keyword(s):  
Neural Networks ◽  
Deep Learning ◽  
Pfam Domain ◽  
Protein Sequences ◽  
Host Cells ◽  
Spike Protein ◽  
Upper Respiratory Tract ◽  
The Neural Network ◽  
Spike Sequences ◽  
Spike Proteins

AbstractMotivationCoronaviridae are a family of positive-sense RNA viruses capable of infecting humans and animals. These viruses usually cause a mild to moderate upper respiratory tract infection, however, they can also cause more severe symptoms, gastrointestinal and central nervous system diseases. These viruses are capable of flexibly adapting to new environments, hence health threats from coronavirus are constant and long-term. Immunogenic spike proteins are glyco-proteins found on the surface of Coronaviridae particles that mediate entry to host cells. The aim of this study was to train deep learning neural networks to produce simulated spike protein sequences, which may be able to aid in knowledge and/or vaccine design by creating alternative possible spike sequences that could arise from zoonotic sources in future.ResultsHere we have trained deep learning recurrent neural networks (RNN) to provide computer-simulated coronavirus spike protein sequences in the style of previously known sequences and examine their characteristics. Training used a dataset of alpha, beta, gamma and delta coronavirus spike sequences. In a test set of 100 simulated sequences, all 100 had most significant BLAST matches to Spike proteins in searches against NCBI non-redundant dataset (NR) and also possessed concomitant Pfam domain matches.ConclusionsSimulated sequences from the neural network may be able to guide us in future with prospective targets for vaccine discovery in advance of a potential novel zoonosis. We may effectively be able to fast-forward through evolution using neural networks to investigate sequences that could arise.

scholarly journals The discovery of potential natural products for targeting SARS-CoV-2 spike protein by virtual screening

2020 ◽  
Author(s):  
Guan-Yu Chen ◽  
Tsung-You Yao ◽  
Azaj Ahmed ◽  
Yi-Cheng Pan ◽  
Juan-Cheng Yang ◽  
...  
Keyword(s):  
Natural Products ◽  
Virtual Screening ◽  
Virus Infection ◽  
Host Cells ◽  
Spike Protein ◽  
Viral Receptor ◽  
Sinularia Flexibilis ◽  
Complex Protein ◽  
Potential Inhibitors ◽  
Spike Proteins

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters into the cells through its spike proteins binding to human angiotensin-converting enzyme 2 (ACE2) protein and causes virus infection in host cells. Until now, there are no available antiviral drugs have been reported that can effectively block virus infection. The study aimed to discover the potential compounds to prevent viral spike proteins to bind to the human ACE2 proteins from Taiwan Database of Extracts and Compounds (TDEC) by structure-based virtual screening. In this study, to rapidly discover potential inhibitors against SARS-CoV-2 spike proteins, the molecular docking calculation was performed by AutoDock Vina program. Herein, we found that 39 potential compounds may have good binding affinities and can respectively bind to the viral receptor-binding domain (RBD) of spike protein in the prefusion conformation and spike-ACE2 complex protein in silico. Among those compounds, especially natural products thioflexibilolide A and candidine that were respectively isolated from the soft corals Sinularia flexibilis and Phaius mishmensis may have better binding affinity than others. This study provided the predictions that these compounds may have the potential to prevent SARS-CoV-2 spike protein from entry into cells.

Development of a high-throughput platform for screening lipid nanoparticles for mRNA delivery

Nanoscale ◽  
2022 ◽  
Author(s):  
Lili Cui ◽  
Sara Pereira ◽  
Silvia Sonzini ◽  
Sally Van Pelt ◽  
Steven Romanelli ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
High Throughput ◽  
Intracellular Delivery ◽  
Lipid Nanoparticles

mRNA lipid nanoparticles (LNPs) are at the forefront of nucleic acid intracellular delivery, as exemplified by the recent emergency approval of two mRNA LNP-based COVID-19 vaccines. The success of an...

scholarly journals Recombinant Viruses for Cancer Therapy

Biomedicines ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 94 ◽  
Author(s):  
Daria Chulpanova ◽  
Valeriya Solovyeva ◽  
Kristina Kitaeva ◽  
Stephen Dunham ◽  
Svetlana Khaiboullina ◽  
...  
Keyword(s):  
Immune Response ◽  
Cancer Therapy ◽  
Immune Surveillance ◽  
Oncolytic Viruses ◽  
Host Cells ◽  
Therapeutic Goals ◽  
Recombinant Viruses ◽  
Wide Range ◽  
Anti Cancer ◽  
Specific Antigens

Recombinant viruses are novel therapeutic agents that can be utilized for treatment of various diseases, including cancers. Recombinant viruses can be engineered to express foreign transgenes and have a broad tropism allowing gene expression in a wide range of host cells. They can be selected or designed for specific therapeutic goals; for example, recombinant viruses could be used to stimulate host immune response against tumor-specific antigens and therefore overcome the ability of the tumor to evade the host’s immune surveillance. Alternatively, recombinant viruses could express immunomodulatory genes which stimulate an anti-cancer immune response. Oncolytic viruses can replicate specifically in tumor cells and induce toxic effects leading to cell lysis and apoptosis. However, each of these approaches face certain difficulties that must be resolved to achieve maximum therapeutic efficacy. In this review we discuss actively developing approaches for cancer therapy based on recombinant viruses, problems that need to be overcome, and possible prospects for further development of recombinant virus based therapy.

scholarly journals Ode to Oseltamivir and Amantadine?

2006 ◽  
Vol 17 (1) ◽  
pp. 11-14 ◽  
Author(s):  
JM Conly ◽  
BL Johnston
Keyword(s):  
Influenza A ◽  
Antigenic Variation ◽  
Interleukin 1 ◽  
Influenza Viruses ◽  
Host Cells ◽  
Surface Glycoprotein ◽  
Influenza B ◽  
Influenza A Viruses ◽  
Epidemic Disease ◽  
Specific Antigens

Influenza A and B viruses are the two major types of influenza viruses that cause human epidemic disease. Influenza A viruses are further categorized into subtypes based on two surface antigens: hemagglutinin (H) and neuraminidase (N). Influenza B viruses are not categorized into subtypes (1). Influenza A viruses are found in many animal species, including humans, ducks, chickens, pigs, whales, horses and seals, whereas influenza B viruses circulate only among humans. The H antigen contains common and strain-specific antigens, demonstrates antigenic variation, and acts as a site of attachment of the virus to host cells to initiate infection (1). The N antigen contains subtype-specific antigens and also demonstrates antigenic variation between subtypes. It is a surface glycoprotein possessing enzymatic activity essential for viral replication in both influenza A and B viruses. The N antigen allows the release of newly produced virions from infected host cells, prevents the formation of viral aggregates after release from the host cells, and prevents viral inactivation by respiratory mucous (2,3). It is thought that this enzyme may also promote viral penetration into respiratory epithelial cells and may contribute to the pathogenicity of the virus by promoting production of proinflammatory cytokines such as interleukin-1 and tumour necrosis factor from macrophages (4-6).

scholarly journals Immunotherapy with Dendritic Cells Directed against Tumor Antigens Shared with Normal Host Cells Results in Severe Autoimmune Disease

2000 ◽  
Vol 191 (5) ◽  
pp. 795-804 ◽  
Author(s):  
Burkhard Ludewig ◽  
Adrian F. Ochsenbein ◽  
Bernhard Odermatt ◽  
Denise Paulin ◽  
Hans Hengartner ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Autoimmune Disease ◽  
Tumor Antigen ◽  
Tumor Antigens ◽  
Islet Cells ◽  
Autoimmune Diabetes ◽  
Host Cells ◽  
Primary Immune Response ◽  
Specific Antigens ◽  
Secondary Lymphoid Organs

Vaccination with dendritic cells (DCs) presenting tumor antigens induces primary immune response or amplifies existing cytotoxic antitumor T cell responses. This study documents that antitumor treatment with DCs may cause severe autoimmune disease when the tumor antigens are not tumor-specific but are also expressed in peripheral nonlymphoid organs. Growing tumors with such shared tumor antigens that were, at least initially, strictly located outside of secondary lymphoid organs were successfully controlled by specific DC vaccination. However, antitumor treatment was accompanied by fatal autoimmune disease, i.e., autoimmune diabetes in transgenic mice expressing the tumor antigen also in pancreatic β islet cells or by severe arteritis, myocarditis, and eventually dilated cardiomyopathy when arterial smooth muscle cells and cardiomyocytes expressed the transgenic tumor antigen. These results reveal the delicate balance between tumor immunity and autoimmunity and therefore point out important limitations for the use of not strictly tumor-specific antigens in antitumor vaccination with DCs.

scholarly journals Impact of Thiol-Disulfide Balance on the Binding of Covid-19 Spike Protein with Angiotensin Converting Enzyme 2 Receptor

2020 ◽  
Author(s):  
Sanchita Hati ◽  
Sudeep Bhattacharyya
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Binding Affinity ◽  
Disulfide Bonds ◽  
Host Cells ◽  
Converting Enzyme ◽  
Dynamic Simulations ◽  
Angiotensin Converting Enzyme 2 ◽  
Novel Coronavirus ◽  
The Impact ◽  
Spike Proteins

AbstractThe novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to an ongoing pandemic of coronavirus disease (COVID-19), which started in 2019. This is a member of Coronaviridae family in the genus Betacoronavirus, which also includes SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). The angiotensin-converting enzyme 2 (ACE2) is the functional receptor for SARS-CoV and SARS-CoV-2 to enter the host cells. In particular, the interaction of viral spike proteins with ACE2 is a critical step in the viral replication cycle. The receptor binding domain of the viral spike proteins and ACE2 have several cysteine residues. In this study, the role of thiol-disulfide balance on the interactions between SARS-CoV/CoV-2 spike proteins and ACE2 was investigated using molecular dynamic simulations. The study revealed that the binding affinity was significantly impaired when all the disulfide bonds of both ACE2 and SARS-CoV/CoV-2 spike proteins were reduced to thiol groups. The impact on the binding affinity was less severe when the disulfide bridges of only one of the binding partners were reduced to thiols. This computational finding provides a molecular basis for the severity of COVID-19 infection due to the oxidative stress.

scholarly journals Introduction of Two Prolines and Removal of the Polybasic Cleavage Site Lead to Higher Efficacy of a Recombinant Spike-Based SARS-CoV-2 Vaccine in the Mouse Model

mBio ◽  
2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Fatima Amanat ◽  
Shirin Strohmeier ◽  
Raveen Rathnasinghe ◽  
Michael Schotsaert ◽  
Lynda Coughlan ◽  
...  
Keyword(s):  
Mouse Model ◽  
Cleavage Site ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Host Cells ◽  
Spike Protein ◽  
Optimized Design ◽  
Angiotensin Converting Enzyme 2 ◽  
Viral Target ◽  
Spike Proteins

ABSTRACT The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified as the prime target for vaccine development. The spike protein mediates both binding to host cells and membrane fusion and is also so far the only known viral target of neutralizing antibodies. Coronavirus spike proteins are large trimers that are relatively unstable, a feature that might be enhanced by the presence of a polybasic cleavage site in SARS-CoV-2 spike. Exchange of K986 and V987 for prolines has been shown to stabilize the trimers of SARS-CoV-1 and the Middle East respiratory syndrome coronavirus spike proteins. Here, we test multiple versions of a soluble spike protein for their immunogenicity and protective effect against SARS-CoV-2 challenge in a mouse model that transiently expresses human angiotensin-converting enzyme 2 via adenovirus transduction. Variants tested include spike proteins with a deleted polybasic cleavage site, proline mutations, or a combination thereof, besides the wild-type protein. While all versions of the protein were able to induce neutralizing antibodies, only the antigen with both a deleted cleavage site and the K986P and V987P (PP) mutations completely protected from challenge in this mouse model. IMPORTANCE A vaccine for SARS-CoV-2 is urgently needed. A better understanding of antigen design and attributes that vaccine candidates need to have to induce protective immunity is of high importance. The data presented here validate the choice of antigens that contain the PP mutations and suggest that deletion of the polybasic cleavage site may lead to a further-optimized design.

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