scholarly journals Unique Peptide Signatures Of SARS-CoV-2 Against Human Proteome Reveal Variants’ Immune Escape And Infectiveness

2021 ◽  
Author(s):  
Vasileios Pierros ◽  
Evangelos Kontopodis ◽  
Dimitrios J. Stravopodis ◽  
George Th. Tsangaris
Keyword(s):  
Immune Escape ◽  
Human Proteome ◽  
Receptor Protein ◽  
Sequence Length ◽  
Host Organism ◽  
Antigenic Sites ◽  
Extensive Analysis ◽  
Novel Approach ◽  
Notable Increase ◽  
Simultaneous Existence

SummarySARS-CoV-2 pandemic has emerged the necessity of the identification of sequences sites in viral proteome appropriate as antigenic sites and treatment targets. In the present study, we apply a novel approach for deciphering the virus-host organism interaction, by analyzing the Unique Peptides of the virus with a minimum amino acid sequence length defined as Core Unique Peptides (CrUPs) not of the virus per se, but against the entire proteome of the host organism. The result of this approach is the identification of the CrUPs of the virus itself, which do not appear in the host organism proteome. Thereby, we analyzed the SARS-CoV-2 proteome for identification of CrUPs against the Human Proteome and they are defined as C/H-CrUPs. We found that SARS-CoV-2 include 7.503 C/H-CrUPs, with the SPIKE_SARS2 being the protein with the highest density of C/H-CrUPs. Extensive analysis indicated that the P681R mutation produces new C/H-CrUPs around the R685 cleavage site, while the L452R mutation induces the loss of antigenicity of the NF9 peptide and the strong(er) binding of the virus to ACE2 receptor protein. The simultaneous existence of these mutations in variants like Delta results in the immune escape of the virus, its massive entrance into the host cell, a notable increase in virus formation, and its massive release and thus elevated infectivity.

Immunocytochemical localization of nicotinic acetylcholine receptors in the terminal abdominal ganglion of the cockroach ( Periplaneta americana )

1989 ◽  
Vol 238 (1291) ◽  
pp. 189-192 ◽  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Periplaneta Americana ◽  
Specific Binding ◽  
Neuronal Cell ◽  
Abdominal Ganglion ◽  
Receptor Protein ◽  
Nicotinic Acetylcholine ◽  
Antigenic Sites ◽  
Neuronal Cell Bodies

A polyclonal, monospecific antiserum raised against a nicotinic acetylcholine receptor protein affinity-purified from insect nervous tissue, was employed to demonstrate the localization of antigenic sites in the neuropile of the terminal (sixth) abdominal ganglion of the cockroach Periplaneta americana . In agreement with previously published autoradiographic mapping of specific [ 125 I] α -bungarotoxin binding sites, specific areas of the central neuropile of this ganglion were densely stained, but not the cereal afferent axons. No staining was detected corresponding to the dense, peripheral, partly non-specific binding of α -bungarotoxin seen in autoradiographs of the same tissue. Certain peripherally located neuronal cell bodies, including the cell body of giant interneuron 2, contained intracellularly located antigenic sites.

Therapeutic Targeting of Inflammatory Pathways with Emphasis on NLRP3 Inflammasomes by Natural Products: A Novel Approach for the Treatment of Inflammatory Eye Diseases

2021 ◽  
Vol 28 ◽  
Author(s):  
Amro M. Soliman ◽  
Ru Hui Sim ◽  
Srijit Das ◽  
Pasuk Mahakkannurauh
Keyword(s):  
Natural Products ◽  
Nlrp3 Inflammasome ◽  
Conventional Medicine ◽  
Eye Diseases ◽  
Receptor Protein ◽  
Inflammatory Pathways ◽  
Novel Approach ◽  
Underlying Mechanisms ◽  
Nlrp3 Inflammasomes ◽  
Herbal Formulations

: There is an increase in the incidence of inflammatory eye diseases worldwide. Several dysregulated inflammatory pathways, including the NOD-like receptor protein 3 (NLRP3) inflammasome, have been reported to contribute significantly to the pathogenesis and progression of ophthalmic diseases. Although the available allopathic/conventional medicine has demonstrated effectiveness in managing eye diseases, there is an ongoing global demand for alternative therapeutics with minimal adverse drug reactions, easy availability, increase in patient-compliance, and better disease outcome. Therefore, several studies are investigating the utilization of natural products and herbal formulations in impeding inflammatory pathways, including the NLRP3 inflammasome, in order to prevent or manage eye diseases. In the present review, we highlight the recently reported inflammatory pathways with special emphasis on NLRP3 Inflammasomes involved in the development of eye diseases. Furthermore, we present a variety of natural products and phytochemicals that were reported to interfere with these pathways and their underlying mechanisms of action. These natural products represent potential therapeutic applications for the treatment of several inflammatory eye diseases.

scholarly journals Pharmaceutical cold chain and novel technological tools: a systematic review

TRANSPORTES ◽  
2021 ◽  
Vol 29 (1) ◽  
pp. 67-85
Author(s):  
Giset N. Montoya M. ◽  
Orlando Fontes Lima Jr. ◽  
Antonio G. N. Novaes ◽  
Jose Benedito S. Santos Jr. ◽  
Jaime A.C. Arias
Keyword(s):  
Supply Chain ◽  
Cold Chain ◽  
Research Progress ◽  
Decision Making Process ◽  
Market Growth ◽  
Extensive Analysis ◽  
Novel Approach ◽  
Technological Advances ◽  
Technological Tools ◽  
The Impact

The pharmaceutical cold chain (PCC) deals with specific logistics operational require-ments related to product quality, safety, and regulations that make the supply chain management process complex. Also, the pharma industry market growth increases the awareness, in terms of good's temperature monitoring and controlling, of the storage and transportation processes across the network. This study provides a novel approach to PCC, based on a systematic literature review with an extensive analysis of the main aspects that influence the supply chain processes. The major findings highlight the recently worldwide research progress on the PCC subjects related, the challenges involving the PCC and its associated technological advances based on three attributes (product characteristics, vehicle capabilities, and logistics service provider’s expertise) and, finally, the impact of technologies and its potential utilization to im-prove the decision-making process on integrated cold chain operations.  

scholarly journals Comprehensive mapping of binding hot spots of SARS-CoV-2 RBD-specific neutralizing antibodies for tracking immune escape variants

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Chunyan Yi ◽  
Xiaoyu Sun ◽  
Yixiao Lin ◽  
Chenjian Gu ◽  
Longfei Ding ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Immune Escape ◽  
Early Stage ◽  
Neutralizing Antibody ◽  
Additive Effect ◽  
Escape Mutation ◽  
Prospective Surveillance ◽  
Antibody Recognition ◽  
Antigenic Sites ◽  
The Impact

Abstract Background The receptor-binding domain (RBD) variants of SARS-CoV-2 could impair antibody-mediated neutralization of the virus by host immunity; thus, prospective surveillance of antibody escape mutants and understanding the evolution of RBD are urgently needed. Methods Using the single B cell cloning technology, we isolated and characterized 93 RBD-specific antibodies from the memory B cells of four COVID-19 convalescent individuals in the early stage of the pandemic. Then, global RBD alanine scanning with a panel of 19 selected neutralizing antibodies (NAbs), including several broadly reactive NAbs, was performed. Furthermore, we assessed the impact of single natural mutation or co-mutations of concern at key positions of RBD on the neutralization escape and ACE2 binding function by recombinant proteins and pseudoviruses. Results Thirty-three amino acid positions within four independent antigenic sites (1 to 4) of RBD were identified as valuable indicators of antigenic changes in the RBD. The comprehensive escape mutation map not only confirms the widely circulating strains carrying important immune escape RBD mutations such as K417N, E484K, and L452R, but also facilitates the discovery of new immune escape-enabling mutations such as F486L, N450K, F490S, and R346S. Of note, these escape mutations could not affect the ACE2 binding affinity of RBD, among which L452R even enhanced binding. Furthermore, we showed that RBD co-mutations K417N, E484K, and N501Y present in B.1.351 appear more resistant to NAbs and human convalescent plasma from the early stage of the pandemic, possibly due to an additive effect. Conversely, double mutations E484Q and L452R present in B.1.617.1 variant show partial antibody evasion with no evidence for an additive effect. Conclusions Our study provides a global view of the determinants for neutralizing antibody recognition, antigenic conservation, and RBD conformation. The in-depth escape maps may have value for prospective surveillance of SARS-CoV-2 immune escape variants. Special attention should be paid to the accumulation of co-mutations at distinct major antigenic sites. Finally, the new broadly reactive NAbs described here represent new potential opportunities for the prevention and treatment of COVID-19.

scholarly journals A Novel Approach for Facial Attendance:AttendXNet

2020 ◽  
Vol 2 (2) ◽  
pp. 104-111
Author(s):  
Ankur Singh Bist
Keyword(s):  
Deep Learning ◽  
Facial Recognition ◽  
Use Cases ◽  
Feed Forward ◽  
Extensive Analysis ◽  
Novel Approach ◽  
Feed Forward Network ◽  
State Of Art

Recent advancements in the area of facial recognition and verification introduced thepossibility of facial attendance for various use cases. In this paper we present a system namedas AttendXNet. Our method uses the ResNet and Multi-layer feed forward network to achievethe state of art results. Extensive analysis of various deep learning and machine learningtechniques is described. Face anti-spoofing is a major challenge in facial attendance.Extended-MobileNet is used to resolve the same issue. We also introduced the end to endpipeline to implement an attendance system for various use cases.

Influenza Vaccine Effectiveness: Defining the H3N2 Problem

2019 ◽  
Vol 69 (10) ◽  
pp. 1817-1823 ◽  
Author(s):  
Edward A Belongia ◽  
Huong Q McLean
Keyword(s):  
Influenza Vaccine ◽  
Observational Studies ◽  
Immune Escape ◽  
Neutralizing Antibody ◽  
Vaccine Effectiveness ◽  
Type B ◽  
Contributing Factors ◽  
Antigenic Sites ◽  
Technology Platforms ◽  
Antigenic Evolution

Abstract Observational studies have consistently shown that influenza vaccine effectiveness (VE) is lower for H3N2 relative to H1N1pdm09 and type B, and this is not entirely explained by antigenic match. The triad of virus, vaccine, and host immunity provides a framework to examine contributing factors. Antigenic evolution facilitates H3N2 immune escape, and increasing glycosylation of the hemagglutinin shields antigenic sites from antibody binding. Egg passage adaptation of vaccine viruses generates mutations that alter glycosylation, impair the neutralizing antibody response, and reduce VE. Complex host immune factors may also influence H3N2 VE, including early childhood imprinting and repeated vaccination, but their role is uncertain. Of the triad of contributing factors, only changes to the vaccine are readily achievable. However, it is unclear whether current licensed non–egg-based vaccines generate superior protection against H3N2. The optimal strategy remains to be defined, but newer vaccine technology platforms offer great potential.

scholarly journals Modelling the role of immunity in reversion of viral antigenic sites

2015 ◽  
Author(s):  
Carmen H. S. Chan ◽  
Lloyd P. Sanders ◽  
Mark M. Tanaka
Keyword(s):  
Influenza A ◽  
Evolutionary Dynamics ◽  
Immune Escape ◽  
Low Cost ◽  
Synonymous Substitution ◽  
Host Immunity ◽  
Viral Population ◽  
Viral Pathogens ◽  
Site Model ◽  
Antigenic Sites

Antigenic sites in viral pathogens exhibit distinctive evolutionary dynamics due to their role in evading recognition by host immunity. Antigenic selection is known to drive higher rates of non-synonymous substitution; less well understood is why differences are observed between viruses in their propensity to mutate to a novel or previously encountered amino acid. Here, we present a model to explain patterns of antigenic reversion and forward substitution in terms of the epidemiological and molecular processes of the viral population. We develop an analytical three-strain model and extend the analysis to a multi-site model to predict characteristics of observed sequence samples. Our model provides insight into how the balance between selection to escape immunity and to maintain viability is affected by the rate of mutational input. We also show that while low probabilities of reversion may be due to either a low cost of immune escape or slowly decaying host immunity, these two scenarios can be differentiated by the frequency patterns at antigenic sites. Comparison between frequency patterns of human influenza A (H3N2) and human RSV-A suggests that the increased rates of antigenic reversion in RSV-A is due to faster decaying immunity and not higher costs of escape.

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