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. 2020 Oct;13(10):1544-1550.
doi: 10.1016/j.jiph.2020.06.030. Epub 2020 Jul 1.

Evolving sequence mutations in the Middle East Respiratory Syndrome Coronavirus (MERS-CoV)

Mohammed Ali AlBalwi  1 , Anis Khan  2 , Mohammed AlDrees  3 , Udayaraja Gk  4 , Balavenkatesh Manie  4 , Yaseen Arabi  5 , Ibrahim Alabdulkareem  6 , Sameera AlJohani  7 , Majed Alghoribi  3 , Ahmed AlAskar  3 , Abdulaziz AlAjlan  7 , Ali Hajeer  7
Affiliations

Evolving sequence mutations in the Middle East Respiratory Syndrome Coronavirus (MERS-CoV)

Mohammed Ali AlBalwi et al. J Infect Public Health. 2020 Oct.

Abstract

Background: Middle East respiratory syndrome coronavirus (MERS-CoV) has continued to cause sporadic outbreaks of severe respiratory tract infection over the last 8 years.

Methods: Complete genome sequencing using next-generation sequencing was performed for MERS-CoV isolates from cases that occurred in Riyadh between 2015 and 2019. Phylogenetic analysis and molecular mutational analysis were carried out to investigate disease severity.

Results: A total of eight MERS-CoV isolates were subjected to complete genome sequencing. Phylogenetic analysis resulted in the assembly of 7/8 sequences within lineage 3 and one sequence within lineage 4 showing complex genomic recombination. The isolates contained a variety of unique amino acid substitutions in ORF1ab (41), the N protein (10), the S protein (9) and ORF4b (5).

Conclusion: Our study shows that MERS-CoV is evolving. The emergence of new variants carries the potential for increased virulence and could impose a challenge to the global health system. We recommend the sequencing every new MERS-CoV isolate to observe the changes in the virus and relate them to clinical outcomes.

Keywords: MERS-CoV; SARS-CoV; Saudi Arabia; Substitutions; Zoonosis.

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Figures

Fig. 1
Fig. 1
A near-complete phylogenetic analysis of Middle East respiratory syndrome coronavirus (MERS-CoV) genomes. This maximum likelihood tree was estimated from sequences >30,000 nt in length (n = 111), including those of six newly sequenced isolates from Saudi Arabia, using RAxML. The names of viruses sequenced in this work are shown in red. Camel viruses are indicated by bold circles, while all other samples are from human infections. Branch lengths reflect the number of nucleotide substitutions per site. Intra- and inter-lineage genetic distances (p-distance) are shown in the inset.
Fig. 2
Fig. 2
Phylogenetic analysis of the Middle East respiratory syndrome coronavirus (MERS-CoV) based on partial ORF1 (A), ORF2 (B), and S gene (C) regions. These maximum likelihood trees were estimated with the inclusion of six newly sequenced isolates from Saudi Arabia using RAxML. The names of viruses sequenced in this work are shown in red. Camel viruses are indicated by bold circles, while all other samples are from human infections. Branch lengths reflect the number of nucleotide substitutions per site. Intra- and inter-lineage genetic distances (p-distance) are shown in the inset.
Fig. 3
Fig. 3
Bootscan analysis demonstrating the complex recombination of MH013216. Mers-CoV strains representing lineages 1-6 of group B along with strains from group A were subjected to bootscan analysis across the complete genome using the Simplot program with a 200-bp window size, 20-bp step size, and 100 bootstrap replicates using gap-stripped alignments and neighbour-joining analysis. Vertical lines show the common estimated breakpoints of recombination in the analysed strains vs MH013216.
See this image and copyright information in PMC

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