The authors have declared that no competing interests exist.
The goal of this paper is to obtain the numerical consensus of B cell epitopes from the three-dimensional structure of the prefusion spike glycoprotein of the new betacoronavirus that could lead to the development of a vaccine to 2019-nCoV. In order to do that, we first calculated the B-cell epitopes that are predicted using fourteen different mathematical algorithms. Later, we obtained the consensus of B-cell epitopes according to the Similarity Index, and finally selecting the best candidates according to the results of a function called <F> which is evaluated for the glycoprotein. The best candidates that we obtained in order to design a vaccine are SSANNCT, PLQSYGFQPT, TESNKKFLP, NNSYEC, AENS, LPDPSK and YDPLQPE.
On March 11 a new epidemic of an unusual pneumonia appearing to originate in the Huanan Seafood Market in Wuhan (China) was eventually declared to be a pandemic. More than 150,000 cases of 2019-nCoV infected until March 10, 2020, and almost 6000 deaths in almost 140 countries in the world. Unfortunately there currently is no vaccine to fight this disease.
In January 2020, Chen
With these results, it is possible to determine the B-cell epitopes that could be the basis for developing a vaccine, it means, it is basically residues present on the surface of an antigen that stimulates humoral immune responses
In 2015, a computational methodology was published that allowed quantifying the quantification of the B cell epitopes employing a function called <F>, which is based on structural and energy factors evaluated in this glycoprotein which includes the degree of exposure to the solvent, the mobility, and the Gibbs free energy. Only the first of the three factors have been previously used in the scientific literature
Therefore, the function <F> will be defined as follows:
where <Q> is the average value obtained from the Similarity Index; δΔG is the sum of all the values obtained from the free energy changes, and <R> is the average value of the mobility of the amino acids. In the next section we will explain how these values are calculated.
An important aspect is to verify the degree of solvent exposure of the region from where the epitopes come, and for to calculate it, we average values obtained from two different computer programs. Therefore, the work will calculated the consensus of B-cell epitopes derived from the spike glycoprotein of the 2019-nCoV, filtered according to the values of the function <F>, and the degree of solvent exposure.
From the sequence and three dimensional structure of the spike (S) glycoprotein obtained from PDB, we calculated the linear and conformational B-cell epitopes with the following computational programs: BePiPred
The next step was to determine the consensus of the B-cell epitopes according to the procedure described by Isea
In parallel, the contributions of the Gibbs free energy was calculated with the PoPMuSiC program
On the other hand, the mobility associated with each epitope, abbreviated as <R>, was obtained with the elNémo program
It is necessary to verify that these epitopes come from a region exposed to the solvent, and for this reason, it was determined from the average value obtained from two different computer programs: PoPMuSiC
Thus, the best candidates to select a vaccine against this disease should be those with the lowest value of the <F> function and the highest degree of solvent exposure. These last two criteria have been set in the present work and must be verified with experimental results
We have obtained 373 B-cell epitopes according to results obtained from the sequence and the three-dimensional structure of the spike glycoprotein (PDB ID) 6VSB as detailed below: 24 linear B-cell epitopes (the threshold is 0,35) yields with the BePiPred 2.0 program. The ABCPred predicted 49 epitopes of the length of 10 amino acids whose score is equal to or greater than 0,66. The BCPred program based on the hydrophilicity, flexible, accessibility and exposed surface were predicted 15, 14, 30 and 8, respectively. The Emili procedure generated 22 epitopes with a threshold of 1 and a window size of 6; and Kolasar antigenic were 37 (threshold 1,044 and windows size = 7). Discotope 1.1 (threshold = -7,7) yields 19, and ElliPro was 14 (minimum score = 0,5 and maximum distance = 6 Å). CBTope (threshold = -0.3) predicted 31, COBEpro (threshold = 0 .69) was 59, SEPPA 3.0 was 41 and finally SVMTripP was 10 (windows size = 10 and threshold = 0.325).
The next step was to calculate the consensus of B cell epitopes and the function <F>. To visualize this calculation, we let us focus on the region between 276 to 287 amino acids as show in
In the first and second columns of
Pos. | Amino Acid | Q | R | Mutation | Polyview | PoPMuSiC solvent |
276 | L | 2 | 2.73 | 1.68 | 0 | 0.27 |
277 | L | 2 | 2.96 | 2.33 | 0 | 0 |
278 |
|
|
3.22 | 0.04 | 3 | 34.98 |
279 |
|
|
3.75 | 2.51 | 0 | 2.18 |
280 |
|
|
4.19 | 0.63 | 3 | 39.07 |
281 |
|
|
4.94 | 0.51 | 3 | 33.60 |
282 |
|
|
4.95 | 0.81 | 4 | 48.86 |
283 |
|
|
4.49 | 2.24 | 0 | 2.49 |
284 |
|
|
3.99 | 0.88 | 3 | 29.27 |
285 | I | 3 | 3.39 | 1.72 | 0 | 2.38 |
286 | T | 4 | 3.26 | 0.75 | 3 | 37.94 |
287 | D | 4 | 2.79 | 0.36 | 4 | 39.51 |
The value
Therefore the value of the function <F> obtained from the glycoprotein and extrapolate to the consensus of B cell epitope KYNENGT is equal to 10,31 (
|
|
|
|
|
---|---|---|---|---|
39-46 | PDKVFRSS | 5,75 | 9,38 | 0,23 |
108-115 | TTLDSKTQ | 7,13 | 8,19 | 0,34 |
161-167 |
|
5,71 | 3,74 | 0,46 |
172-175 | SQPF | 5,50 | 3,60 | 0,29 |
207-217 | HTPINLVRDLP | 6,00 | 15,48 | 0,37 |
278-284 | KYNENGT | 5,71 | 10,31 | 0,26 |
307-326 | TVEKGIYQTSNFRVQPTESI | 5,40 | 28,36 | 0,33 |
351-362 | YAWNRKRISNCV | 6,92 | 4,87 | 0,33 |
404-431 | GDEVRQIAPGQTGKIADYNYKLPDDFTG | 6,79 | 4,06 | 0,28 |
491-500 |
|
6,10 | 0,67 | 0,43 |
517-532 | LLHAPATVCGPKKSTN | 6,50 | 4,55 | 0,36 |
553-561 |
|
7,33 | 4,74 | 0,45 |
602-608 | TNTSNQV | 5,86 | 9,06 | 0,48 |
657-662 |
|
5,33 | 4,77 | 0,53 |
701-704 |
|
5,50 | 1,15 | 0,52 |
706-709 | AYSN | 6,00 | 5,29 | 0,39 |
772-779 | VEQDKNTQ | 6,63 | 6,57 | 0,23 |
786-796 | KQIYKTPPIKD | 6,82 | 6,30 | 0,34 |
806-815 |
|
9,33 | 5,77 | 0,51 |
983-989 | RLDPPEA | 6,00 | 2,84 | 0,26 |
1035-1039 | GQSKR | 6,00 | 15,26 | 0,17 |
1138-1144 |
|
5,86 | 2,59 | 0,45 |
The results in
The present work calculated the consensus linear and conformational B-cell epitopes from a new coronavirus 2019-nCoV obtained from spike glycoprotein. With this information, it may be possible to design a vaccine for this disease. We employed a function called <F> that considers energy factors and the structure of the glycoprotein for selected the best candidates of B cell epitopes. Finally, the next step is to begin to validate these results with
The author wishes to thank Karl E. Lonngren for his suggestions in this work.