PMC:7245302 / 17445-24588 JSONTXT 11 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T133 0-327 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 328-508 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 509-690 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 691-871 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 872-1010 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 1011-1198 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 1199-1508 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 1509-1743 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 1744-1848 Sentence denotes Next, enumeration of transmembrane helices in the pooled 174 mice non-similar proteins was accomplished.
T142 1849-1990 Sentence denotes This transmembrane topology characterization is deemed vital in relatedness to the afterward experimental expression studies of the proteins.
T143 1991-2209 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 2210-2274 Sentence denotes This result 33 proteins spanning across five types, and include:
T145 2275-2879 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 2880-3045 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 3046-3142 Sentence denotes The idea behind exploiting adhesin for a vaccine is based on the promising preclinical findings.
T148 3143-3620 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 3621-3826 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 3827-4043 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 4044-4236 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 4237-4535 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 4536-4653 Sentence denotes Nsp9 is a non-structural protein 9, key to coronavirus replication and is a single-stranded RNA-binding protein [63].
T154 4654-4738 Sentence denotes Nsp10 is a critical cofactor that switches on multiple enzymes in replication cycle.
T155 4739-5038 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 5039-5209 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 5210-5336 Sentence denotes The surface glycoprotein was analyzed to be different in a sequence patch (Leu3-Phe11) at the start of the spike glycoprotein.
T158 5337-5634 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 5635-5760 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 5761-5909 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 5910-5957 Sentence denotes Nsp8 DRDAAMQRK 0.8641 35.81 non-allergen 1.0606
T162 5958-6000 Sentence denotes QARSEDKRA 0.5770 24.15 non-allergen 1.0606
T163 6001-6056 Sentence denotes Proteinase EDMLNPNYEDL 1.0913 21.68 non-allergen 1.0600
T164 6057-6098 Sentence denotes EFTPFDVVR 1.6049 5.07 non-allergen 1.0604
T165 6099-6162 Sentence denotes Spike Glycoprotein VNNSYECDIPI 1.0996 23.93 non-allergen 1.0593
T166 6163-6245 Sentence denotes Table 2 Top 10 refined models of the MEPVC along with the initial input structure.
T167 6246-6320 Sentence denotes Model RMSD MolProbity Clash score Poor rotamers Rama favored GALAXY energy
T168 6321-6363 Sentence denotes Initial 0.000 3.312 95.9 3.8 93.6 20995.70
T169 6364-6405 Sentence denotes MODEL 1 1.734 1.134 1.2 0.0 95.7 -3784.31
T170 6406-6447 Sentence denotes MODEL 2 1.920 1.444 2.4 0.0 93.6 -3750.72
T171 6448-6489 Sentence denotes MODEL 3 1.766 0.997 0.6 0.0 95.7 -3743.81
T172 6490-6531 Sentence denotes MODEL 4 1.667 0.997 0.6 0.0 95.7 -3739.43
T173 6532-6573 Sentence denotes MODEL 5 2.611 1.187 0.9 1.3 95.2 -3731.44
T174 6574-6615 Sentence denotes MODEL 6 1.782 1.187 0.9 1.3 95.2 -3724.93
T175 6616-6657 Sentence denotes MODEL 7 2.907 1.144 1.5 0.0 96.3 -3722.41
T176 6658-6699 Sentence denotes MODEL 8 1.999 1.459 3.0 0.6 94.7 -3718.59
T177 6700-6741 Sentence denotes MODEL 9 3.194 1.192 1.8 0.0 96.3 -3715.99
T178 6742-6784 Sentence denotes MODEL 10 2.235 1.310 2.7 0.6 96.3 -3713.14
T179 6785-6910 Sentence denotes Fig. 2 The final set of potential vaccine candidates filtered through several in silico checks presented as interactive Venn.
T180 6911-7143 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).