Tags

Type your tag names separated by a space and hit enter

Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant.
J Transl Med. 2020 04 22; 18(1):179.JT

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 < 0.001).

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.

Authors+Show Affiliations

Elettra Sincrotrone Trieste - Area Science Park, Trieste, Italy. Department of Physics, University of Trieste, Via Valerio 2, Trieste, Italy.Ulisse BioMed - Area Science Park, Trieste, Italy.Institute of Human Virology, Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, USA.Department of Medicine, Surgery and Health Science, University of Trieste, Trieste, Italy.Ulisse BioMed - Area Science Park, Trieste, Italy.Elettra Sincrotrone Trieste - Area Science Park, Trieste, Italy.Elettra Sincrotrone Trieste - Area Science Park, Trieste, Italy.Medical Statistic and Molecular Epidemiology Unit, University of Biomedical Campus, Rome, Italy.Medical Statistic and Molecular Epidemiology Unit, University of Biomedical Campus, Rome, Italy.Institute of Human Virology, Department of Medicine, School of Medicine, University of Maryland, Baltimore, USA. Co-founder and International Science Advisor - Global Virus Network, Baltimore, USA.Institute of Human Virology, Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, USA. DZella@ihv.umaryland.edu. Member of the Global Virus Network, Baltimore, USA. DZella@ihv.umaryland.edu.Ulisse BioMed - Area Science Park, Trieste, Italy. r.ippodrino@ulissebiomed.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32321524

Citation

Pachetti, Maria, et al. "Emerging SARS-CoV-2 Mutation Hot Spots Include a Novel RNA-dependent-RNA Polymerase Variant." Journal of Translational Medicine, vol. 18, no. 1, 2020, p. 179.
Pachetti M, Marini B, Benedetti F, et al. Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant. J Transl Med. 2020;18(1):179.
Pachetti, M., Marini, B., Benedetti, F., Giudici, F., Mauro, E., Storici, P., Masciovecchio, C., Angeletti, S., Ciccozzi, M., Gallo, R. C., Zella, D., & Ippodrino, R. (2020). Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant. Journal of Translational Medicine, 18(1), 179. https://doi.org/10.1186/s12967-020-02344-6
Pachetti M, et al. Emerging SARS-CoV-2 Mutation Hot Spots Include a Novel RNA-dependent-RNA Polymerase Variant. J Transl Med. 2020 04 22;18(1):179. PubMed PMID: 32321524.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant. AU - Pachetti,Maria, AU - Marini,Bruna, AU - Benedetti,Francesca, AU - Giudici,Fabiola, AU - Mauro,Elisabetta, AU - Storici,Paola, AU - Masciovecchio,Claudio, AU - Angeletti,Silvia, AU - Ciccozzi,Massimo, AU - Gallo,Robert C, AU - Zella,Davide, AU - Ippodrino,Rudy, Y1 - 2020/04/22/ PY - 2020/03/31/received PY - 2020/04/11/accepted PY - 2020/4/24/entrez PY - 2020/4/24/pubmed PY - 2020/4/28/medline KW - COVID-19 KW - Drug resistance KW - Europe KW - Mutation KW - Pneumonia KW - RNA-dependent-RNA-polymerase KW - RdRp KW - SARS-CoV-2 KW - Viral mutagenesis SP - 179 EP - 179 JF - Journal of translational medicine JO - J Transl Med VL - 18 IS - 1 N2 - 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 < 0.001). 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. SN - 1479-5876 UR - https://www.unboundmedicine.com/medline/citation/32321524/Emerging_SARS_CoV_2_mutation_hot_spots_include_a_novel_RNA_dependent_RNA_polymerase_variant_ L2 - https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-020-02344-6 DB - PRIME DP - Unbound Medicine ER -