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Incipient functional SARS-CoV-2 diversification identified through neural network haplotype maps.

Soledad Delgado1, Pilar Somovilla2,3, Cristina Ferrer-Orta4

  • 1Departamento de Sistemas Informáticos, Escuela Técnica Superior de Ingeniería de Sistemas Informáticos, Universidad Politécnica de Madrid, Madrid 28031, Spain.

Proceedings of the National Academy of Sciences of the United States of America
|February 28, 2024
PubMed
Summary
This summary is machine-generated.

SARS-CoV-2 intrahost diversification reveals mutations impacting RNA synthesis. These key mutations were identified in COVID-19 patients during the early pandemic phase.

Keywords:
COVID-19clade transitionintrahost evolutionself-organized mapsviral quasispecies

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Area of Science:

  • Virology
  • Molecular Biology
  • Genomics

Background:

  • SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) has rapidly evolved into diverse clades since its emergence.
  • Understanding intrahost diversification events within individual patients is crucial for tracking viral evolution.

Purpose of the Study:

  • To investigate the intrahost diversification of SARS-CoV-2.
  • To identify mutations affecting viral RNA synthesis during early stages of the pandemic.

Main Methods:

  • Analysis of SARS-CoV-2 haplotype repertoires from nasopharyngeal samples using 3D self-organized neural haplotype maps (SOMs).
  • Focus on mutant spectra within the nsp12 and spike (S)-coding regions.
  • In vitro primer extension assays to assess RNA synthesis kinetics of identified mutations.

Main Results:

  • SOMs revealed dominant and low-frequency mutant clouds within viral quasispecies.
  • Six deviant haplotype sequences were identified in master neurons.
  • Mutations in the neural clouds affected the nsp12-nsp8-nsp7 polymerase complex, altering RNA synthesis kinetics.

Conclusions:

  • Identified mutations are relevant to SARS-CoV-2 RNA synthesis modification.
  • These mutations likely arose during intrahost diversification in COVID-19 patients early in the pandemic.