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Viral Mutations00:36

Viral Mutations

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A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
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Single Nucleotide Polymorphisms-SNPs01:05

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A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
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Mutations01:39

Mutations

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Overview
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Mutations01:35

Mutations

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Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
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Point and Frameshift Mutations01:30

Point and Frameshift Mutations

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Point mutations are genetic alterations involving the change of a single nucleotide base pair in DNA. Depending on how the alteration affects protein synthesis, they can lead to various consequences.Point mutations fall into the following types:Silent mutations occur when a nucleotide change does not alter the amino acid sequence due to the redundancy of the genetic code. For instance, changing ACC to ACA still encodes threonine, leaving the protein function unaffected. This occurs because...
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Mutations in Microorganisms01:18

Mutations in Microorganisms

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Mutations are heritable changes in an organism’s genome involving alterations in the base sequence of DNA or RNA. These changes can influence cellular processes and phenotypic traits, potentially transforming the unaltered wild type into a mutant form. Such changes, termed forward mutations, are pivotal in shaping the genetic diversity of organisms.RNA viruses exhibit the highest mutation rates due to the absence of robust proofreading mechanisms during genome replication. In contrast,...
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Engineering Antiviral Agents via Surface Plasmon Resonance
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Human SARS CoV-2 spike protein mutations.

Lalitha Guruprasad1

  • 1School of Chemistry, University of Hyderabad, Hyderabad, India.

Proteins
|January 10, 2021
PubMed
Summary

This study analyzed over 10,000 severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike proteins, identifying 9,654 mutations across 400 sites. Key mutations in the receptor binding domain (RBD) are crucial for understanding COVID-19 and developing new treatments.

Keywords:
SARS-CoV-2mutationsreceptor binding domainsequence and structural mappingspike proteins

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Area of Science:

  • Virology
  • Structural Biology
  • Immunology

Background:

  • Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein is critical for viral entry and a primary target for vaccines and therapeutics.
  • Mutations in the spike protein can affect viral transmissibility, immune evasion, and disease severity.
  • Geographical distribution of viral mutations provides insights into viral evolution and spread.

Purpose of the Study:

  • To analyze the geographical distribution and characteristics of mutations in SARS-CoV-2 spike proteins globally.
  • To identify specific mutations within the receptor binding domain (RBD) that interact with the human ACE-2 receptor.
  • To provide data relevant for the development of antibodies, vaccines, and drugs against SARS-CoV-2.

Main Methods:

  • Comparative analysis of 10,333 human spike protein sequences from diverse geographical locations against the Wuhan-Hu-1 reference sequence.
  • Identification and quantification of mutations, mutation sites, and mutation types.
  • Analysis of mutations within the RBD, focusing on residues near the ACE-2 binding interface.
  • Examination of mutation density and location in the 3D structure of the spike protein.

Main Results:

  • Out of 10,333 analyzed spike protein sequences, 8,155 contained one or more mutations.
  • A total of 9,654 mutations were identified across 400 distinct mutation sites.
  • The RBD contained 44 mutations, including those at residues critical for ACE-2 receptor interaction.
  • Mutations showed varying distributions across geographical regions and different functional sites of the spike protein.

Conclusions:

  • The identified mutations in SARS-CoV-2 spike proteins, particularly in the RBD, have significant implications for viral infectivity and host interactions.
  • Understanding the geographical and structural distribution of these mutations is essential for effective pandemic response.
  • These findings are critical for guiding the development of next-generation vaccines, monoclonal antibodies, and antiviral therapies.