Analysis of the Genome Sequence and Prediction of B-Cell Epitopes of the Envelope Protein of Middle East Respiratory Syndrome-Coronavirus

The outbreak of Middle East respiratory syndrome-coronavirus (MERS-CoV) in South Korea in April 2015 led to 186 infections and 37 deaths by the end of October 2015. MERS-CoV was isolated from the imported patient in China. The envelope (E) protein, a small structural protein of MERS-CoV, plays an important role in host recognition and infection. To identify the conserved epitopes of the E protein, sequence analysis was performed by comparing the E proteins from 42 MERS-CoV strains that triggered severe pandemics and infected humans in the past. To predict the potential B cell epitopes of E protein, three most effective online epitope prediction programs, the ABCpred, Bepipred, and Protean programs from the LaserGene software were used. All the nucleotides and amino acids sequences were obtained from the NCBI Database. One potential epitope with a suitable length (amino acids 58–82) was confirmed and predicted to be highly antigenic. This epitope had scores of >0.80 in ABCpred and level 0.35 in Bepipred programs. Due to the lack of X-ray crystal structure of the E protein in the PDB database, the simulated 3D structure of the E protein were also predicted using PHYRE 2 and Pymol programs. In conclusion, using bioinformatics methods, we analyzed the genome sequence of MERS-CoV and identified a potential B-cell epitope of the E protein, which might significantly improve our current MERS vaccine development strategies.

[1]  K. Nishikawa.  Assessment of secondary-structure prediction of proteins. Comparison of computerized Chou-Fasman method with others. , 1983, Biochimica et biophysica acta.

[2]  Russ B. Altman,et al.  WebFEATURE: an interactive web tool for identifying and visualizing functional sites on macromolecular structures , 2003, Nucleic Acids Res..

[3]  Elliot J. Lefkowitz,et al.  Virus taxonomy: classification and nomenclature of viruses , 2012 .

[4]  Alexander E. Gorbalenya,et al.  Genomic Characterization of a Newly Discovered Coronavirus Associated with Acute Respiratory Distress Syndrome in Humans , 2012, mBio.

[5]  Morten Nielsen,et al.  Improved method for predicting linear B-cell epitopes , 2006, Immunome research.

[6]  Michael J E Sternberg,et al.  The Phyre2 web portal for protein modeling, prediction and analysis , 2015, Nature Protocols.

[7]  R. Doolittle,et al.  A simple method for displaying the hydropathic character of a protein. , 1982, Journal of molecular biology.

[8]  Astrid Gall,et al.  Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive genomic study , 2013, The Lancet.

[9]  Vasant G Honavar,et al.  Predicting linear B‐cell epitopes using string kernels , 2008, Journal of molecular recognition : JMR.

[10]  Jing Chen,et al.  Small envelope protein E of SARS: cloning, expression, purification, CD determination, and bioinformatics analysis. , 2003, Acta pharmacologica Sinica.

[11]  A. Osterhaus,et al.  Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. , 2012, The New England journal of medicine.

[12]  R. Hodges,et al.  New hydrophilicity scale derived from high-performance liquid chromatography peptide retention data: correlation of predicted surface residues with antigenicity and X-ray-derived accessible sites. , 1986, Biochemistry.

[13]  Sudipto Saha,et al.  Prediction of continuous B‐cell epitopes in an antigen using recurrent neural network , 2006, Proteins.

[14]  Lanjuan Li,et al.  Molecular Characteristics, Functions, and Related Pathogenicity of MERS-CoV Proteins , 2019, Engineering.

[15]  E. Emini,et al.  Induction of hepatitis A virus-neutralizing antibody by a virus-specific synthetic peptide , 1985, Journal of virology.

[16]  Y. Guan,et al.  Coronavirus as a possible cause of severe acute respiratory syndrome , 2003, The Lancet.

[17]  M.H.V. Van Regenmortel,et al.  An assessment of prediction methods for locating continuous epitopes in proteins. , 1988 .

[18]  P. Zhou,et al.  Identification of immunogenic determinants of the spike protein of SARS-like coronavirus , 2013, Virologica Sinica.

[19]  Christian Drosten,et al.  Identification of a novel coronavirus in patients with severe acute respiratory syndrome. , 2003, The New England journal of medicine.

[20]  Sangdun Choi,et al.  Middle East respiratory syndrome coronavirus: transmission, virology and therapeutic targeting to aid in outbreak control , 2015, Experimental & Molecular Medicine.

[21]  Bao Zhang,et al.  Genomic sequencing and analysis of the first imported Middle East Respiratory Syndrome Coronavirus (MERS CoV) in China , 2015, Science China Life Sciences.

[22]  H. Vennema,et al.  Characterization of the Coronavirus Mouse Hepatitis Virus Strain A59 Small Membrane Protein E , 2000, Journal of Virology.

[23]  K. R. Woods,et al.  Prediction of protein antigenic determinants from amino acid sequences. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[24]  B. A. Jameson,et al.  The antigenic index: a novel algorithm for predicting antigenic determinants , 1988, Comput. Appl. Biosci..

[25]  Mohit Kamthania,et al.  Structural basis of development of multi-epitope vaccine against Middle East respiratory syndrome using in silico approach , 2018, Infection and drug resistance.

[26]  J. Torres,et al.  MERS coronavirus envelope protein has a single transmembrane domain that forms pentameric ion channels , 2015, Virus Research.

[27]  W. Delano.  The PyMOL Molecular Graphics System (2002) , 2002 .

[28]  W. Tan,et al.  Recent Advances in the Vaccine Development Against Middle East Respiratory Syndrome-Coronavirus , 2019, Front. Microbiol..