scholarly journals Recombination and Point Mutations in Type G Rotavirus Strains: The Challenges of Vaccine Development

10.5772/33629 ◽  
2012 ◽  
Author(s):  
Abid Nabil Ben Salem ◽  
Rouis Zyed ◽  
Buesa Javier ◽  
Aouni Mahjoub
Keyword(s):  
Vaccine Development ◽  
Point Mutations

scholarly journals Stabilizing the Closed SARS-CoV-2 Spike Trimer

2020 ◽  
Author(s):  
Jarek Juraszek ◽  
Lucy Rutten ◽  
Sven Blokland ◽  
Pascale Bouchier ◽  
Richard Voorzaat ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Single Point ◽  
Point Mutations ◽  
Heptad Repeat ◽  
S Protein ◽  
Single Point Mutations ◽  
Primary Focus ◽  
Immunogenic Properties ◽  
Serological Diagnostics ◽  
Selection Of

AbstractThe trimeric spike (S) protein of SARS-CoV-2 is the primary focus of most vaccine design and development efforts. Due to intrinsic instability typical of class I fusion proteins, S tends to prematurely refold to the post-fusion conformation, compromising immunogenic properties and prefusion trimer yields. To support ongoing vaccine development efforts, we report the structure-based design of soluble S trimers, with increased yields and stabilities, based on introduction of single point mutations and disulfide-bridges. We identify two regions in the S-protein critical for the protein’s stability: the heptad repeat region 1 of the S2 subunit and subunit domain 1 at the interface with S2. We combined a minimal selection of mostly interprotomeric mutations to create a stable S-closed variant with a 6.4-fold higher expression than the parental construct while no longer containing a heterologous trimerization domain. The cryo-EM structure reveals a correctly folded, predominantly closed pre-fusion conformation. Highly stable and well producing S protein and the increased understanding of S protein structure will support vaccine development and serological diagnostics.

Identification of unique mutations in SARS-CoV-2 strains isolated from India suggests its attenuated pathotype

2020 ◽  
Author(s):  
Shubham Gaurav ◽  
Shambhavi Pandey ◽  
Apurvasinh Puvar ◽  
Tejas Shah ◽  
Madhvi Joshi ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Early Stage ◽  
Point Mutations ◽  
Economic Losses ◽  
Multiple Point ◽  
Genomic Information ◽  
Dynamic Nature ◽  
Remarkable Similarity ◽  
Nucleotide Deletion ◽  
Unique Ability

AbstractSevere Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which was first reported in Wuhan, China in November 2019 has developed into a pandemic since March 2020, causing substantial human casualties and economic losses. Studies on SARS-CoV-2 are being carried out at an unprecedented rate to tackle this threat. Genomics studies, in particular, are indispensable to elucidate the dynamic nature of the RNA genome of SARS-CoV-2. RNA viruses are marked by their unique ability to undergo high rates of mutation in their genome, much more frequently than their hosts, which diversifies their strengths qualifying them to elude host immune response and amplify drug resistance. In this study, we sequenced and analyzed the genomic information of the SARS-CoV-2 isolates from two infected Indian patients and explored the possible implications of point mutations in its biology. In addition to multiple point mutations, we found a remarkable similarity between relatively common mutations of 36-nucleotide deletion in ORF8 of SARS-CoV-2. Our results corroborate with the earlier reported 29-nucleotide deletion in SARS, which was frequent during the early stage of human-to-human transmission. The results will be useful to understand the biology of SARS-CoV-2 and itsattenuation for vaccine development.

scholarly journals Norovirus: Clinical Findings and Pharmaceutical Developments

2021 ◽  
Author(s):  
Ying-Fei Yang ◽  
Chung-Min Liao
Keyword(s):  
Clinical Trials ◽  
Vaccine Development ◽  
Antiviral Drug ◽  
Point Mutations ◽  
Clinical Findings ◽  
Protection Mechanism ◽  
Healthcare Facilities ◽  
Travel Industry ◽  
High Immunogenicity

Norovirus (NoV) is one of the most ubiquitous factors contributing to acute gastroenteritis that causes widespread outbreaks in travel industry, military, or healthcare facilities. NoV could lead to serious symptoms and result in severe societal costs worldwide. Surprisingly, there has been no available licensed vaccines, albeit there are ongoing pre-clinical or clinical trials of several candidate vaccines. Development of effective universal vaccines has been found difficult clinically due to the frequent point mutations and a lack of robust animal model and cell culture system. Preclinical studies showed that vaccines with virus-like particles (VLPs) have high immunogenicity and efficacies and were demonstrated to be protective and safe. Recent in vitro research also suggests that human intestinal enteroids can enhance our understanding of protection mechanism and give guidance for vaccine development. Overall, this chapter will give a comprehensive review of the current challenge and progress of clinical findings, efficacy/safety of the developing vaccines, and antiviral drug developments for NoV in clinical trials or preclinical investigations.

scholarly journals Impact of Structural Observables From Simulations to Predict the Effect of Single-Point Mutations in MHC Class II Peptide Binders

2021 ◽  
Vol 8 ◽  
Author(s):  
Rodrigo Ochoa ◽  
Roman A. Laskowski ◽  
Janet M. Thornton ◽  
Pilar Cossio
Keyword(s):  
Molecular Dynamics ◽  
Mhc Class Ii ◽  
Vaccine Development ◽  
Single Point ◽  
Point Mutations ◽  
Class Ii ◽  
Scoring Method ◽  
Scoring Matrices ◽  
Scoring Matrix ◽  
Single Point Mutations

The prediction of peptide binders to Major Histocompatibility Complex (MHC) class II receptors is of great interest to study autoimmune diseases and for vaccine development. Most approaches predict the affinities using sequence-based models trained on experimental data and multiple alignments from known peptide substrates. However, detecting activity differences caused by single-point mutations is a challenging task. In this work, we used interactions calculated from simulations to build scoring matrices for quickly estimating binding differences by single-point mutations. We modelled a set of 837 peptides bound to an MHC class II allele, and optimized the sampling of the conformations using the Rosetta backrub method by comparing the results to molecular dynamics simulations. From the dynamic trajectories of each complex, we averaged and compared structural observables for each amino acid at each position of the 9°mer peptide core region. With this information, we generated the scoring-matrices to predict the sign of the binding differences. We then compared the performance of the best scoring-matrix to different computational methodologies that range in computational costs. Overall, the prediction of the activity differences caused by single mutated peptides was lower than 60% for all the methods. However, the developed scoring-matrix in combination with existing methods reports an increase in the performance, up to 86% with a scoring method that uses molecular dynamics.

Detection of Ki-ras gene point mutations in the bile precipitate of patients with various cause of billiary obstruction

2001 ◽  
Vol 120 (5) ◽  
pp. A574-A574
Author(s):  
C CHEN ◽  
S SHIESH ◽  
H TSAO ◽  
X LIN
Keyword(s):  
Point Mutations ◽  
Ras Gene

Fiberoptic DNA sensor array capable of detecting point mutations

1998 ◽  
Vol 13 (2) ◽  
pp. iv-v ◽  
Author(s):  
B Healey
Keyword(s):  
Sensor Array ◽  
Point Mutations ◽  
Dna Sensor

A Novel Mutation Glyl672→Arg in Type 2A and a Homozygous Mutation in Type 2B von Willebrand Disease

1996 ◽  
Vol 76 (02) ◽  
pp. 253-257 ◽  
Author(s):  
Takeshi Hagiwara ◽  
Hiroshi Inaba ◽  
Shinichi Yoshida ◽  
Keiko Nagaizumi ◽  
Morio Arai ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Novel Mutation ◽  
Point Mutations ◽  
Japanese Patients ◽  
Von Willebrand Disease ◽  
Homozygous Mutation ◽  
Missense Mutations ◽  
Reaction Products ◽  
Type 3 ◽  
Von Willebrand

SummaryGenetic materials from 16 unrelated Japanese patients with von Willebrand disease (vWD) were analyzed for mutations. Exon 28 of the von Willebrand factor (vWF) gene, where point mutations have been found most frequent, was screened by various restriction-enzyme analyses. Six patients were observed to have abnormal restriction patterns. By sequence analyses of the polymerase chain-reaction products, we identified a homozygous R1308C missense mutation in a patient with type 2B vWD; R1597W, R1597Q, G1609R and G1672R missense mutations in five patients with type 2A; and a G1659ter nonsense mutation in a patient with type 3 vWD. The G1672R was a novel missense mutation of the carboxyl-terminal end of the A2 domain. In addition, we detected an A/C polymorphism at nucleotide 4915 with HaeIII. There was no particular linkage disequilibrium of the A/C polymorphism, either with the G/A polymorphism at nucleotide 4391 detected with Hphl or with the C/T at 4891 detected with BstEll.

PREVALENCE OF COMMON MITOCHONDRIAL POINT MUTATIONS IN AUTISM

2006 ◽  
Vol 37 (S 1) ◽  
Author(s):  
FJ Serajee ◽  
H Zhong ◽  
AHMM Huq
Keyword(s):  
Point Mutations

Point Mutations in the AML1/RUNX1 Gene Associated with Myelodysplastic Syndrome

2005 ◽  
Vol 15 (3) ◽  
pp. 183-196 ◽  
Author(s):  
Hironori Harada ◽  
Yuka Harada
Keyword(s):  
Myelodysplastic Syndrome ◽  
Point Mutations ◽  
Runx1 Gene
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