key: cord-0990043-90hgp4em
authors: Yeh, Ting‐Yu; Contreras, Gregory P
title: Emerging viral mutants in Australia suggest RNA recombination event in the SARS‐CoV‐2 genome
date: 2020-06-07
journal: Med J Aust
DOI: 10.5694/mja2.50657
sha: e630b3b3c750cf662beab33a06ef901f38566aff
doc_id: 990043
cord_uid: 90hgp4em

nan

To the Editor: The coronavirus disease 2019 (COVID-19) outbreak has become a public health emergency globally. 1, 2 Until 26 May 2020, there were 7126 confirmed cases reported in Australia (https://coron avirus.jhu.edu/map.html). However, specimens of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) independently isolated in Australia (in Sydney, the Gold Coast and Melbourne) 3 exhibited very unusual mutations, which have not been identified in other countries (Box, A).

Up to 29 April, 1319 sequences of the Australian SARS-CoV-2 isolates are available in the website of the Global Initiative on Sharing All Influenza Data (GISAID). 3 Except for the NSW03 and NSW01 isolates, viral mutations are located at the stem-loop II motif (s2m), an extremely conserved RNA element in the 3' untranslated region (3'-UTR) (Box, A). The NSW02 and VIC01 isolates have deletion of 41 and ten nucleotides respectively. All Queensland cases have single G-to-A substitution (nucleotides 29714/QLD01, 29736/QLD02, 29736/ QLD04, and 29737/QLD03). Moreover, patients with NSW05, NSW06, NSW07, NSW15, NSW18, NSW19, NSW21, NSW24, NSW26, NSW28, or NSW31 (nucleotide 29696) have single G-to-U substitution at the same nucleotide. This substitution is only present in Australian patients and has not been found in SARS-CoV-2 isolates from other countries.

Phylogenetic analysis showed that SARS and 30 other coronaviruses and astroviruses all possess the genetic element s2m, suggesting that this motif is conserved in both nucleotide sequence and secondary structure folding during evolution in an otherwise rapidly mutable RNA genome. 3, 5 The three-dimensional crystal structure of the s2m RNA element of the SARS virus shows that guanosine (19), which is mutated in Australian isolates, is critical for tertiary contacts to form an RNA base quartet involving two adjacent G-C pairs (G19, C20, G28, and C31) 4 (Box, B) . Because s2m plays an essential role for the viral RNA to substitute host protein synthesis, we hypothesise that the disruption of s2m could alter the viral viability or infectivity dramatically.

The s2m sequence of coronaviruses is highly conserved, and spontaneous mutations in this motif were not expected to have occurred during the apparent short period when SARS-CoV-2 has been present; therefore, it is highly likely that the changes are due to recombination. 5 Because a high frequency of recombination events in coronaviruses occurs, RNA recombination could either enhance the adaptation process to its new host like humans or cause unpredictable changes in virulence during infection.

Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding

COVID-19 National Incident Room Surveillance Team; Department of Health. COVID-19

EpiCoV: pandemic coronavirus causing COVID-19

The structure of a rigorously conserved RNA element within the SARS virus genome

Distribution and evolutionary history of the mobile genetic element s2m in coronaviruses