Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant

• Published in: Journal of translational medicine 2020-04, Vol.18 (1), p.179-9, Article 179
• Main Authors: Pachetti, Maria, Marini, Bruna, Benedetti, Francesca, Giudici, Fabiola, Mauro, Elisabetta, Storici, Paola, Masciovecchio, Claudio, Angeletti, Silvia, Ciccozzi, Massimo, Gallo, Robert C, Zella, Davide, Ippodrino, Rudy
• Format: Article
• Language: English
• Subjects: Adult; Amino acid composition; Amino acids; Analysis; Asia; Asia - epidemiology; Betacoronavirus - genetics; Coronavirus Infections - drug therapy; Coronavirus Infections - epidemiology; Coronavirus Infections - mortality; Coronavirus Infections - virology; Coronaviruses; COVID-19; DNA-directed RNA polymerase; Drug delivery; Drug resistance; Drug Resistance, Viral - genetics; Enzymes; Epidemics; Europe; Europe - epidemiology; Evolution, Molecular; Female; Gene mutation; Genes; Genetic aspects; Genome, Viral - genetics; Genomes; Genomics; Health aspects; Humans; Hydrophobicity; Male; Middle Aged; Mortality; Mutation; Mutation hot spots; Mutation Rate; Mutation rates; North America; North America - epidemiology; Oceania - epidemiology; Pandemics; Phenotypes; Pneumonia, Viral - drug therapy; Pneumonia, Viral - epidemiology; Pneumonia, Viral - mortality; Pneumonia, Viral - virology; RdRp; RNA; RNA polymerases; RNA viruses; RNA-Dependent RNA Polymerase - antagonists & inhibitors; RNA-Dependent RNA Polymerase - genetics; RNA-Dependent RNA Polymerase - metabolism; SARS-CoV-2; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Viruses
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-020-02344-6

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. 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. 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