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Signal hotspot mutations in SARS-CoV-2 genomes evolve as the virus spreads and actively replicates in different parts of the world.
Virus Res. 2020 11; 289:198170.VR

Abstract

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) was first identified in Wuhan, China late in 2019. Nine months later (Sept. 23, 2020), the virus has infected > 31.6 million people around the world and caused > 971.000 (3.07 %) fatalities in 220 countries and territories. Research on the genetics of the SARS-CoV-2 genome, its mutants and their penetrance can aid future defense strategies. By analyzing sequence data deposited between December 2019 and end of May 2020, we have compared nucleotide sequences of 570 SARS-CoV-2 genomes from China, Europe, the US, and India to the sequence of the Wuhan isolate. During worldwide spreading among human populations, at least 10 distinct hotspot mutations had been selected and found in up to > 80 % of viral genomes. Many of these mutations led to amino acid exchanges in replication-relevant viral proteins. Mutations in the SARS-CoV-2 genome would also impinge upon the secondary structure of the viral RNA molecule and its repertoire of interactions with essential cellular and viral proteins. The increasing frequency of SARS-CoV-2 mutation hotspots might select for dangerous viral pathogens. Alternatively, in a 29.900 nucleotide-genome, there might be a limit to the number of mutable and selectable sites which, when exhausted, could prove disadvantageous to viral survival. The speed, at which novel SARS-CoV-2 mutants are selected and dispersed around the world, could pose problems for the development of vaccines and therapeutics.

Authors+Show Affiliations

Institute for Clinical and Molecular Virology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg, 91054, Erlangen, Germany.Department of Biostatistics, UCLA School of Public Health, Los Angeles, CA, 90095-1772, USA.Institute for Clinical and Molecular Virology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg, 91054, Erlangen, Germany; Institute of Genetics, University of Cologne, 50674, Cologne, Germany. Electronic address: walter.doerfler@t-online.de.

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32979477

Citation

Weber, Stefanie, et al. "Signal Hotspot Mutations in SARS-CoV-2 Genomes Evolve as the Virus Spreads and Actively Replicates in Different Parts of the World." Virus Research, vol. 289, 2020, p. 198170.
Weber S, Ramirez C, Doerfler W. Signal hotspot mutations in SARS-CoV-2 genomes evolve as the virus spreads and actively replicates in different parts of the world. Virus Res. 2020;289:198170.
Weber, S., Ramirez, C., & Doerfler, W. (2020). Signal hotspot mutations in SARS-CoV-2 genomes evolve as the virus spreads and actively replicates in different parts of the world. Virus Research, 289, 198170. https://doi.org/10.1016/j.virusres.2020.198170
Weber S, Ramirez C, Doerfler W. Signal Hotspot Mutations in SARS-CoV-2 Genomes Evolve as the Virus Spreads and Actively Replicates in Different Parts of the World. Virus Res. 2020;289:198170. PubMed PMID: 32979477.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Signal hotspot mutations in SARS-CoV-2 genomes evolve as the virus spreads and actively replicates in different parts of the world. AU - Weber,Stefanie, AU - Ramirez,Christina, AU - Doerfler,Walter, Y1 - 2020/09/24/ PY - 2020/08/01/received PY - 2020/09/18/revised PY - 2020/09/19/accepted PY - 2020/9/27/pubmed PY - 2020/10/31/medline PY - 2020/9/26/entrez KW - Consequences for secondary and tertiary structures of viral RNA KW - Impact on replication-relevant viral proteins KW - Questions about immunogenesis and vaccine development KW - Selection of viral hotspot mutations KW - Sequence comparisons between 570 viral genomes to Wuhan isolate KW - Severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) SP - 198170 EP - 198170 JF - Virus research JO - Virus Res VL - 289 N2 - Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) was first identified in Wuhan, China late in 2019. Nine months later (Sept. 23, 2020), the virus has infected > 31.6 million people around the world and caused > 971.000 (3.07 %) fatalities in 220 countries and territories. Research on the genetics of the SARS-CoV-2 genome, its mutants and their penetrance can aid future defense strategies. By analyzing sequence data deposited between December 2019 and end of May 2020, we have compared nucleotide sequences of 570 SARS-CoV-2 genomes from China, Europe, the US, and India to the sequence of the Wuhan isolate. During worldwide spreading among human populations, at least 10 distinct hotspot mutations had been selected and found in up to > 80 % of viral genomes. Many of these mutations led to amino acid exchanges in replication-relevant viral proteins. Mutations in the SARS-CoV-2 genome would also impinge upon the secondary structure of the viral RNA molecule and its repertoire of interactions with essential cellular and viral proteins. The increasing frequency of SARS-CoV-2 mutation hotspots might select for dangerous viral pathogens. Alternatively, in a 29.900 nucleotide-genome, there might be a limit to the number of mutable and selectable sites which, when exhausted, could prove disadvantageous to viral survival. The speed, at which novel SARS-CoV-2 mutants are selected and dispersed around the world, could pose problems for the development of vaccines and therapeutics. SN - 1872-7492 UR - https://www.unboundmedicine.com/medline/citation/32979477/Signal_hotspot_mutations_in_SARS_CoV_2_genomes_evolve_as_the_virus_spreads_and_actively_replicates_in_different_parts_of_the_world_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0168-1702(20)31077-7 DB - PRIME DP - Unbound Medicine ER -