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Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant
- Source :
- Journal of translational medicine, 18(1):179, Journal of Translational Medicine, Journal of Translational Medicine, Vol 18, Iss 1, Pp 1-9 (2020)
- Publication Year :
- 2020
-
Abstract
- Background SARS-CoV-2 is a RNA coronavirus responsible for the pandemic of the Severe Acute Respiratory Syndrome (COVID-19). RNA viruses are characterized by a high mutation rate, up to a million times higher than that of their hosts. Virus mutagenic capability depends upon several factors, including the fidelity of viral enzymes that replicate nucleic acids, as SARS-CoV-2 RNA dependent RNA polymerase (RdRp). Mutation rate drives viral evolution and genome variability, thereby enabling viruses to escape host immunity and to develop drug resistance. Methods We analyzed 220 genomic sequences from the GISAID database derived from patients infected by SARS-CoV-2 worldwide from December 2019 to mid-March 2020. SARS-CoV-2 reference genome was obtained from the GenBank database. Genomes alignment was performed using Clustal Omega. Mann–Whitney and Fisher-Exact tests were used to assess statistical significance. Results We characterized 8 novel recurrent mutations of SARS-CoV-2, located at positions 1397, 2891, 14408, 17746, 17857, 18060, 23403 and 28881. Mutations in 2891, 3036, 14408, 23403 and 28881 positions are predominantly observed in Europe, whereas those located at positions 17746, 17857 and 18060 are exclusively present in North America. We noticed for the first time a silent mutation in RdRp gene in England (UK) on February 9th, 2020 while a different mutation in RdRp changing its amino acid composition emerged on February 20th, 2020 in Italy (Lombardy). Viruses with RdRp mutation have a median of 3 point mutations [range: 2–5], otherwise they have a median of 1 mutation [range: 0–3] (p value Conclusions These findings suggest that the virus is evolving and European, North American and Asian strains might coexist, each of them characterized by a different mutation pattern. The contribution of the mutated RdRp to this phenomenon needs to be investigated. To date, several drugs targeting RdRp enzymes are being employed for SARS-CoV-2 infection treatment. Some of them have a predicted binding moiety in a SARS-CoV-2 RdRp hydrophobic cleft, which is adjacent to the 14408 mutation we identified. Consequently, it is important to study and characterize SARS-CoV-2 RdRp mutation in order to assess possible drug-resistance viral phenotypes. It is also important to recognize whether the presence of some mutations might correlate with different SARS-CoV-2 mortality rates.
- Subjects :
- 0301 basic medicine
Male
Mutation rate
RdRp
viruses
Drug Resistance
lcsh:Medicine
0302 clinical medicine
Mutation Rate
Viral
COVID-19
Drug resistance
Europe
Mutation
Pneumonia
RNA-dependent-RNA-polymerase
SARS-CoV-2
Viral mutagenesis
Adult
Asia
Betacoronavirus
Coronavirus Infections
Drug Resistance, Viral
Female
Genome, Viral
Humans
Middle Aged
North America
Oceania
Pandemics
Pneumonia, Viral
RNA Replicase
Evolution, Molecular
Genetics
Viral mutagenesi
Genome
General Medicine
030220 oncology & carcinogenesis
Viral evolution
Mutation (genetic algorithm)
Human
Silent mutation
Evolution
RNA-dependent RNA polymerase
Biology
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
RNA-Dependent RNA Polymerase
Gene
Betacoronaviru
Pandemic
Coronavirus Infection
Point mutation
Research
lcsh:R
RNA
Molecular
030104 developmental biology
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Journal of translational medicine, 18(1):179, Journal of Translational Medicine, Journal of Translational Medicine, Vol 18, Iss 1, Pp 1-9 (2020)
- Accession number :
- edsair.doi.dedup.....3da8aa2fd94da208c002a5e92e5091a3