- mutation in ORF1ab polyprotein appears as a replacement of proline with leucine at position 323 of RdRp
- P323L mutation associated with increase in mutation rate in the viral genome
- commonly found in severely affected SARS-CoV-2 cases

P323L Mutation

State University of New York at Stony Brook

A mutation in an RNA-dependent RNA polymerase (RdRp) is important to note because of its major role in viral replication and transcription, leading to its tendency to be used as a target in antiviral treatment. A study found two different types of mutations in an RdRp of SARS-CoV-2. One is a silent mutation found in the UK on February 9th, 2020, while a different mutation was first reported in Italy on February 20th, 2020. Since the introduction of a mutation of RdRp in Italy, there was an increase in the number of mutations of the virus in the region. By dividing genomes into two groups: one group with the RdRp mutation and one without, it was shown that the group with the RdRp mutation showed a higher frequency of mutations compared to the group without the RdRp mutation. 

Mutation in RNA-dependent RNA polymerase of SARS-CoV-2 in Europe

Increment of SARS-CoV-2 mutation frequency after RdRp mutation appearance per geographic area. The increment of mutation frequency before and after February 9th, 2020 across the different geographic areas (Asia, Europe, North America) is shown. The figure shows a diminishment of Asian mutations (i.e. 1397, 8782, 11083, 26143 and 28144) that is simultaneous with the appearance of new mutations such as 2891, 3036, 23403 and 28881, when RdRp novel European mutation located at 14408 (in red) occurred. The upper table shows the increment or decrement for each single mutation, per geographic area

Fig 3. Increment of SARS-CoV-2 mutation frequency after RdRp mutation appearance per geographic area

Number of SARS-CoV-2 mutations associated with the RdRp mutation. Genomes were subdivided into two groups: group 1 contains genomes with mutation in position 14408 (RdRp) (n = 53, 4 North America and 49 European), and group 2 without RdRp mutation (n = 84). We further subdivided group 1 and 2 by the number of mutations present in the genome. Genomes in group 1 (red bars) showed an increased number of mutations compared to group 2 (grey bars). Most genomes of groups 1 (86.8%) have at least 3 or 4 mutations, whereas 76.2% of genomes of group 2 have less than 2 mutations. We found that viral strains with RdRp mutation have a median of 3 point mutations [range: 2–5], whereas viral strains with no RdRp mutation have a median of 1 mutation [range: 0–3] (p value < 0.001, Mann–Whitney test)

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