On March 11th 2020, WHO publicly declared the SARS-CoV-2 outbreak as a pandemic. The recent emergence of the novel, human pathogen Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread poses a global health emergency. It is also important to recognize whether the presence of some mutations might correlate with different SARS-CoV-2 mortality rates. Consequently, it is important to study and characterize SARS-CoV-2 RdRp mutation in order to assess possible drug-resistance viral phenotypes. 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. To date, several drugs targeting RdRp enzymes are being employed for SARS-CoV-2 infection treatment.
The contribution of the mutated RdRp to this phenomenon needs to be investigated. 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. Viruses with RdRp mutation have a median of 3 point mutations, otherwise they have a median of 1 mutation (p value < 0.001). 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). Mutations in 2891, 3036, 14408, 2341 positions are predominantly observed in Europe, whereas those located at positions 17746, 1780 are exclusively present in North America. Mann–Whitney and Fisher-Exact tests were used to assess statistical significance.
Genomes alignment was performed using Clustal Omega. SARS-CoV-2 reference genome was obtained from the GenBank database. 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.
Mutation rate drives viral evolution and genome variability, thereby enabling viruses to escape host immunity and to develop drug resistance. 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). RNA viruses are characterized by a high mutation rate, up to a million times higher than that of their hosts. SARS-CoV-2 is a RNA coronavirus responsible for the pandemic of the Severe Acute Respiratory Syndrome (COVID-19).
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