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Updated: Dec 9, 2025

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Where Did SARS-CoV-2 Come From?

Thomas Leitner1, Sudhir Kumar2,3

  • 1Theroretical Biology and Biophysics group, Los Alamos National Laboratory, Los Alamos, NM.

Molecular Biology and Evolution
|September 7, 2020
PubMed
Summary
This summary is machine-generated.

Identifying the zoonotic origin of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is crucial for preventing future pandemics. Current evidence suggests bats are unlikely direct ancestors, and CpG patterns are not definitive biomarkers for intermediate hosts.

Keywords:
SARS-CoV-2evolutionoriginspandemic

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Area of Science:

  • Virology
  • Epidemiology
  • Genomics

Background:

  • The COVID-19 pandemic, caused by SARS-CoV-2, highlights the need to understand zoonotic origins to prevent future epidemics.
  • While Rhinolophus bat Betacoronaviruses have been implicated, their genetic distance from SARS-CoV-2 makes them unlikely direct ancestors.
  • An intermediary host is suspected to bridge the gap between bat coronaviruses and human transmission.

Purpose of the Study:

  • To investigate the zoonotic origin of SARS-CoV-2.
  • To evaluate the utility of genomic CpG dinucleotide patterns as biomarkers for identifying intermediate hosts.
  • To explore potential evolutionary pathways of SARS-CoV-2 before human transmission.

Main Methods:

  • Analysis of genomic CpG dinucleotide patterns in SARS-CoV-2 and related coronaviruses from various hosts.
  • Comparative genomics to assess genetic dissimilarity between bat coronaviruses and SARS-CoV-2.
  • Evaluation of CpG patterns as predictive biomarkers for intermediate hosts or tissues.

Main Results:

  • Genomic CpG patterns initially suggested a canid gastrointestinal tract origin for SARS-CoV-2.
  • Similar CpG patterns were subsequently found in coronaviruses from other hosts, including bats and pangolins.
  • Reduced genomic CpG alone proved to be an unreliable biomarker for pinpointing intermediate hosts.

Conclusions:

  • The direct ancestral link between known bat Betacoronaviruses and SARS-CoV-2 remains unlikely due to significant genetic dissimilarity.
  • Genomic CpG dinucleotide patterns are not sufficiently specific to reliably identify the intermediate host or tissue of SARS-CoV-2 evolution.
  • Further research employing additional biomarkers is necessary to elucidate the zoonotic origin of SARS-CoV-2 and prevent future zoonotic spillover events.