Id |
Subject |
Object |
Predicate |
Lexical cue |
T132 |
0-51 |
Sentence |
denotes |
3.2 Identification of Potential Vaccine Candidates |
T133 |
52-379 |
Sentence |
denotes |
Prioritization of potential vaccine candidates could help in minimizing time, labor cost and resources for developing and optimizing the success of getting an effective vaccine against the pathogen. In total, 193 protein entries were retrieved (S-Table 1 ) and analyzed first for sequence homology with the human host proteome. |
T134 |
380-560 |
Sentence |
denotes |
This was significant to evaluate as homology between virus protein (s) to be used in vaccine designing and the host is likely to cause strong autoimmune reactions in the host [58]. |
T135 |
561-742 |
Sentence |
denotes |
This check identified two proteins: (orf1a polyprotein (Accession id, YP_009725295) and nsp3 (Accession id, YP_009725299) as host homologous thus discarded from further evaluations. |
T136 |
743-923 |
Sentence |
denotes |
Experimental studies of the human vaccines are usually done in mice because of the many practical advantages they provide compared to vaccine research in higher animal models [22]. |
T137 |
924-1062 |
Sentence |
denotes |
The appropriateness of mice as an animal model for vaccine research is defined by its ability to reproduce relevant human physiology [59]. |
T138 |
1063-1250 |
Sentence |
denotes |
Considering this, a homology check was devoted to the pipeline and applied to the filtered human non-similar proteins (191 in number) to ensure the selection of non-similar mice proteins. |
T139 |
1251-1560 |
Sentence |
denotes |
This assessment resultant into shortlisting of Orf1ab polyprotein (Accession ids, QHQ82463, QHD43415, QHR63279, QHR63259, QHQ71962, QHO62106, QHQ71972, QHR63249, QHO60603, QHO62111, QHN73794, QHR84448, QHR63269, QHN73809, QHR63289, and QHO62876) and nsp3 (Accession id, YP_009724389) as mice similar proteins. |
T140 |
1561-1795 |
Sentence |
denotes |
The mice non-similar proteins will aid in discouraging false positive results during in vivo experimentations and accurate interpretation of immune protective efficiency of the prioritized vaccine candidates against the virus [22,60]. |
T141 |
1796-1900 |
Sentence |
denotes |
Next, enumeration of transmembrane helices in the pooled 174 mice non-similar proteins was accomplished. |
T142 |
1901-2042 |
Sentence |
denotes |
This transmembrane topology characterization is deemed vital in relatedness to the afterward experimental expression studies of the proteins. |
T143 |
2043-2261 |
Sentence |
denotes |
Protein with transmembrane helices less than 2 in numbers are often considered as best vaccine candidates as multiple helices make recombinant proteins purification and expression difficult in vaccine development [20]. |
T144 |
2262-2326 |
Sentence |
denotes |
This result 33 proteins spanning across five types, and include: |
T145 |
2327-2931 |
Sentence |
denotes |
Orf3a polyprotein (Accession id, QHQ71974, QHR84450, QHD43417, QHQ71964, QHQ82465, QHO60595, YP_009724391, QHN73811, QHN73796, QHO62878), nsp4 (Accession id, YP_009725300), membrane glycoprotein (Accession id, QHD43419, QHQ71966, QHQ71976, QHQ82467, YP_009724393, QHO60597, QHN73813, QHN73798, QHO62880, QHR84452), membrane protein (Accession id, QHR63283, QHR63263, QHR63273, QHR63293, QHR63253), matrix protein (Accession id, QHO62109, QHO62114), and nonstructural protein NS3 (Accession id, QHR63251, QHR63281, QHR63261, QHR63271, QHR63291) containing multiple helices therefore not proceeded further. |
T146 |
2932-3097 |
Sentence |
denotes |
The creation of adhesin-based vaccines is considered an attractive and effective strategy and is being explored as a solution to number of infectious pathogens [61]. |
T147 |
3098-3194 |
Sentence |
denotes |
The idea behind exploiting adhesin for a vaccine is based on the promising preclinical findings. |
T148 |
3195-3672 |
Sentence |
denotes |
The aim is to confer protective immunity via two main mechanisms: (i) opsonization driven by opsonising antibodies that is capable of binding the target antigen as an immunological tag leading to activation of other components of the host immune system for enhance recognition of the pathogen and subsequent complement system activity and virus killing by phagocytosis, (ii) neutralization driven by adhesin-specific antibodies that block virus binding ability to host tissues. |
T149 |
3673-3878 |
Sentence |
denotes |
The adhesion probability computation revealed 26 protein to have adhesion probability value greater than a threshold as tabulated in S-Table 2 and can be ideal putative vaccine candidates against COVID-19. |
T150 |
3879-4095 |
Sentence |
denotes |
The adhesin probability of protein ranges from 0.593 to 0.796 (mean, 0.645).Antigenicity of proteins was predicted to reflect their ability of binding to products of adaptive immunity: antibodies or T-cell receptors. |
T151 |
4096-4288 |
Sentence |
denotes |
In total, 7 proteins: nsp8, nsp9, nsp10, 3C-like proteinase, spike glycoprotein, surface glycoprotein, and ORF1ab polyprotein were recognized as antigenic and scored higher than the threshold. |
T152 |
4289-4587 |
Sentence |
denotes |
Coronavirus nsp8 suggested having diverse activities, including template-dependent RNA polymerase activities, canonical RNA-dependent RNA polymerases, cofactor function of nsp8 for nsp12-mediated RNA-dependent RNA polymerase activity, and metal ion-dependent RNA 3′ polyadenylation activities [62]. |
T153 |
4588-4705 |
Sentence |
denotes |
Nsp9 is a non-structural protein 9, key to coronavirus replication and is a single-stranded RNA-binding protein [63]. |
T154 |
4706-4790 |
Sentence |
denotes |
Nsp10 is a critical cofactor that switches on multiple enzymes in replication cycle. |
T155 |
4791-5090 |
Sentence |
denotes |
It is known to interact with nsp14 and nsp16 subunits activating their respective 3′-5′ exoribonuclease and 2′-O-methyltransferase functions [64]. The 3C-like proteinase is main cysteine protease and is nonstructural protein number 5 (nsp5) and essential in mediating cleavage of nsp4 to nsp16 [65]. |
T156 |
5091-5261 |
Sentence |
denotes |
The trimeric transmembrane coronavirus spike glycoprotein initiates infectious cycle by binding to a specific receptor on the host membrane followed by viral fusion [66]. |
T157 |
5262-5388 |
Sentence |
denotes |
The surface glycoprotein was analyzed to be different in a sequence patch (Leu3-Phe11) at the start of the spike glycoprotein. |
T158 |
5389-5686 |
Sentence |
denotes |
The ORF1ab is replicase polyprotein cleaved by papain-like protease and 3C-like protease at specific cleavage sites to yield 15 to 16 non-structural proteins (nsps) [67]. The final numbers of potential vaccine candidates obtained in this step by step subtraction phase are presented in Figure 2 . |
T159 |
5687-5812 |
Sentence |
denotes |
Table 1 The final set of selected B-cell derived T-cell epitopes for the potential three vaccine candidates against COVID-19. |
T160 |
5813-5961 |
Sentence |
denotes |
Protein Common B and T-cell Epitopes Antigenicity (cut off score, 0.4) MHCphred (IC50 score, 100 nM) Allergenicity Virulentpred (cut off score, 0.5) |
T161 |
5962-6009 |
Sentence |
denotes |
Nsp8 DRDAAMQRK 0.8641 35.81 non-allergen 1.0606 |
T162 |
6010-6052 |
Sentence |
denotes |
QARSEDKRA 0.5770 24.15 non-allergen 1.0606 |
T163 |
6053-6108 |
Sentence |
denotes |
Proteinase EDMLNPNYEDL 1.0913 21.68 non-allergen 1.0600 |
T164 |
6109-6150 |
Sentence |
denotes |
EFTPFDVVR 1.6049 5.07 non-allergen 1.0604 |
T165 |
6151-6214 |
Sentence |
denotes |
Spike Glycoprotein VNNSYECDIPI 1.0996 23.93 non-allergen 1.0593 |
T166 |
6215-6297 |
Sentence |
denotes |
Table 2 Top 10 refined models of the MEPVC along with the initial input structure. |
T167 |
6298-6372 |
Sentence |
denotes |
Model RMSD MolProbity Clash score Poor rotamers Rama favored GALAXY energy |
T168 |
6373-6415 |
Sentence |
denotes |
Initial 0.000 3.312 95.9 3.8 93.6 20995.70 |
T169 |
6416-6457 |
Sentence |
denotes |
MODEL 1 1.734 1.134 1.2 0.0 95.7 -3784.31 |
T170 |
6458-6499 |
Sentence |
denotes |
MODEL 2 1.920 1.444 2.4 0.0 93.6 -3750.72 |
T171 |
6500-6541 |
Sentence |
denotes |
MODEL 3 1.766 0.997 0.6 0.0 95.7 -3743.81 |
T172 |
6542-6583 |
Sentence |
denotes |
MODEL 4 1.667 0.997 0.6 0.0 95.7 -3739.43 |
T173 |
6584-6625 |
Sentence |
denotes |
MODEL 5 2.611 1.187 0.9 1.3 95.2 -3731.44 |
T174 |
6626-6667 |
Sentence |
denotes |
MODEL 6 1.782 1.187 0.9 1.3 95.2 -3724.93 |
T175 |
6668-6709 |
Sentence |
denotes |
MODEL 7 2.907 1.144 1.5 0.0 96.3 -3722.41 |
T176 |
6710-6751 |
Sentence |
denotes |
MODEL 8 1.999 1.459 3.0 0.6 94.7 -3718.59 |
T177 |
6752-6793 |
Sentence |
denotes |
MODEL 9 3.194 1.192 1.8 0.0 96.3 -3715.99 |
T178 |
6794-6836 |
Sentence |
denotes |
MODEL 10 2.235 1.310 2.7 0.6 96.3 -3713.14 |
T179 |
6837-6962 |
Sentence |
denotes |
Fig. 2 The final set of potential vaccine candidates filtered through several in silico checks presented as interactive Venn. |
T180 |
6963-7195 |
Sentence |
denotes |
The total number of proteins (TPs), filtered to 191 host non-homologous proteins (HNHPs), 174 mouse non-similar proteins (MNSPs), 26 adhesive proteins (APs), 7 antigenic proteins and finally to 3 potential vaccine candidates (PVCs). |