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Open AccessArticle

Molecular Evolution and Structural Mapping of N-Terminal Domain in Spike Gene of Middle East Respiratory Syndrome Coronavirus (MERS-CoV)

1
Department of Research Laboratories, Research Center, King Fahad Medical City, Riyadh 59046, Saudi Arabia
2
Department of Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
3
Infectious Diseases Research Department, King Abdullah International Medical Research Center, Riyadh 11481, Saudi Arabia
4
Medical Specialties Department, King Fahad Medical City, Riyadh 59046, Saudi Arabia
5
Department of Basic Medical Sciences, College of Medicine, King Fahad Medical City, Riyadh 59046, Saudi Arabia
*
Author to whom correspondence should be addressed.
Viruses 2020, 12(5), 502; https://doi.org/10.3390/v12050502
Received: 12 March 2020 / Revised: 23 April 2020 / Accepted: 29 April 2020 / Published: 2 May 2020
(This article belongs to the Section Animal Viruses)
The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a lethal zoonotic pathogen circulating in the Arabian Peninsula since 2012. There is no vaccine for MERS and anti-viral treatment is generally not applicable. We investigated the evolution of the MERS-CoV spike gene sequences and changes in viral loads over time from patients in Saudi Arabia from 2015–2017. All the MERS-CoV strains belonged to lineage 5, and showed high sequence homology (99.9%) to 2017 strains. Recombination analysis showed a potential recombination event in study strains from patients in Saudi Arabia. The spike gene showed eight amino acid substitutions, especially between the A1 and B5 lineage, and contained positively selected codon 1020. We also determined that the viral loads were significantly (p < 0.001) higher in fatal cases, and virus shedding was prolonged in some fatal cases beyond 21 days. The viral concentration peaked during the first week of illness, and the lower respiratory specimens had higher levels of MERS-CoV RNA. The presence of the diversifying selection and the topologies with the structural mapping of residues under purifying selection suggested that codon 1020 might have a role in the evolution of spike gene during the divergence of different lineages. This study will improve our understanding of the evolution of MERS-CoV, and also highlights the need for enhanced surveillance in humans and dromedaries. The presence of amino acid changes at the N-terminal domain and structural mapping of residues under positive selection at heptad repeat 1 provides better insight into the adaptive evolution of the spike gene and might have a potential role in virus-host tropism and pathogenesis. View Full-Text
Keywords: Middle East Respiratory Syndrome Coronavirus; evolution; viral load; spike gene Middle East Respiratory Syndrome Coronavirus; evolution; viral load; spike gene
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Naeem, A.; Hamed, M.E.; Alghoribi, M.F.; Aljabr, W.; Alsaran, H.; Enani, M.A.; Alosaimi, B. Molecular Evolution and Structural Mapping of N-Terminal Domain in Spike Gene of Middle East Respiratory Syndrome Coronavirus (MERS-CoV). Viruses 2020, 12, 502.

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