PMC:7245302 / 17393-24588 JSONTXT 11 Projects

Annnotations TAB TSV DIC JSON TextAE

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).