Tags

Type your tag names separated by a space and hit enter

Molecular Evolution and Structural Mapping of N-Terminal Domain in Spike Gene of Middle East Respiratory Syndrome Coronavirus (MERS-CoV).
Viruses. 2020 05 02; 12(5)V

Abstract

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 2105-2017. 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 im-prove 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.

Authors+Show Affiliations

Department of Research Laboratories, Research Center, King Fahad Medical City, Riyadh 59046, Saudi Arabia.Department of Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.Infectious Diseases Research Department, King Abdullah International Medical Research Center, Riyadh 11481, Saudi Arabia.Department of Research Laboratories, Research Center, King Fahad Medical City, Riyadh 59046, Saudi Arabia.Department of Research Laboratories, Research Center, King Fahad Medical City, Riyadh 59046, Saudi Arabia.Medical Specialties Department, King Fahad Medical City, Riyadh 59046, Saudi Arabia.Department of Research Laboratories, Research Center, King Fahad Medical City, Riyadh 59046, Saudi Arabia. Department of Basic Medical Sciences, College of Medicine, King Fahad Medical City, Riyadh 59046, Saudi Arabia.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32370153

Citation

Naeem, Asif, et al. "Molecular Evolution and Structural Mapping of N-Terminal Domain in Spike Gene of Middle East Respiratory Syndrome Coronavirus (MERS-CoV)." Viruses, vol. 12, no. 5, 2020.
Naeem A, Hamed ME, Alghoribi MF, et al. Molecular Evolution and Structural Mapping of N-Terminal Domain in Spike Gene of Middle East Respiratory Syndrome Coronavirus (MERS-CoV). Viruses. 2020;12(5).
Naeem, A., Hamed, M. E., Alghoribi, M. F., Aljabr, W., Alsaran, H., Enani, M. A., & Alosaimi, B. (2020). Molecular Evolution and Structural Mapping of N-Terminal Domain in Spike Gene of Middle East Respiratory Syndrome Coronavirus (MERS-CoV). Viruses, 12(5). https://doi.org/10.3390/v12050502
Naeem A, et al. Molecular Evolution and Structural Mapping of N-Terminal Domain in Spike Gene of Middle East Respiratory Syndrome Coronavirus (MERS-CoV). Viruses. 2020 05 2;12(5) PubMed PMID: 32370153.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular Evolution and Structural Mapping of N-Terminal Domain in Spike Gene of Middle East Respiratory Syndrome Coronavirus (MERS-CoV). AU - Naeem,Asif, AU - Hamed,Maaweya E, AU - Alghoribi,Majed F, AU - Aljabr,Waleed, AU - Alsaran,Hadel, AU - Enani,Mushira A, AU - Alosaimi,Bandar, Y1 - 2020/05/02/ PY - 2020/03/12/received PY - 2020/04/23/revised PY - 2020/04/29/accepted PY - 2020/5/7/entrez PY - 2020/5/7/pubmed PY - 2020/9/17/medline KW - Evolution KW - Middle East Respiratory Syndrome Coronavirus KW - Spike Gene KW - Viral Load JF - Viruses JO - Viruses VL - 12 IS - 5 N2 - 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 2105-2017. 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 im-prove 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. SN - 1999-4915 UR - https://www.unboundmedicine.com/medline/citation/32370153/Molecular_Evolution_and_Structural_Mapping_of_N_Terminal_Domain_in_Spike_Gene_of_Middle_East_Respiratory_Syndrome_Coronavirus__MERS_CoV__ L2 - https://www.mdpi.com/resolver?pii=v12050502 DB - PRIME DP - Unbound Medicine ER -