LitCovid-sentences  

PMC:7102556 / 7641-14581 JSONTXT 13 Projects

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Id Subject Object Predicate Lexical cue
T50 0-39 Sentence denotes 2 Research and development of vaccines
T51 40-179 Sentence denotes The cellular receptors of SARS-CoV and MERS-CoV have been identified [25,26], and the virion spike (S) glycoprotein, was also well studied.
T52 180-294 Sentence denotes S glycoprotein includes two subunits [27], S1 and S2, resulting from cleavage of the one precursor into two parts.
T53 295-542 Sentence denotes S1 determines the virus host range and cellular tropism with the key functional domain - receptor binding domain (RBD), while S2 contains two tandem domains, heptad repeats 1 (HR1) and heptad repeats 2 (HR2), to mediate virus-cell membrane fusion.
T54 543-997 Sentence denotes It is believed that the fusion process is similar to that of HIV-1 [28]; for example, when S1 binds to the receptor on the cell membrane, the fusion peptide at the N terminus of S2 inserts into the cell membrane, then three HR1s attach to each other in parallel as a trimer, followed by binding of three HR2s separately onto the outside of the trimer to form a 6-helix bundle, thus bringing virus and cell membranes close to each other to trigger fusion.
T55 998-1122 Sentence denotes As the major vaccine target, the S protein has been evaluated in different types of vaccines against infection by CoVs [29].
T56 1123-1285 Sentence denotes Apart from the inactive whole virus particle [30], live attenuated virus with gene deletion [31] , four more vaccines which mainly contain S protein were studied.
T57 1286-1653 Sentence denotes These include a virus-like particle which incorporated S protein into hepatitis virus or influenza virus protein [32,33]; virus vectors, such as modified vaccinia virus Ankara (MVA) or Adenovirus carrying S protein [34,35]; S protein subunit vaccine, like RBD-based protein [29,36]; and DNA vaccine which encodes the full length or part of the S protein gene [37,38].
T58 1654-1757 Sentence denotes Most of them have been tested in mouse models and showed the ability to elicit neutralizing antibodies.
T59 1758-1967 Sentence denotes The first SARS-CoV DNA vaccine was tested in humans only 19 months after the virus sequence was published [38], while the DNA vaccine GLS-5300, the first MERS-CoV vaccine, went to clinical trials in 2016 [39].
T60 1968-2238 Sentence denotes In addition to these conventional vaccines, Liu et al. analyzed the T cell epitopes of SARS-CoV and MERS-CoV, revealed the potential cross-reactivity of the coronaviruses, and assessed the possibility of developing universal vaccines against coronavirus infections [40].
T61 2239-2445 Sentence denotes Most CoVs share a similar viral structure, similar infection pathway, and a similar structure of the S proteins [41], suggesting that similar research strategies should also be applicable for the 2019-nCoV.
T62 2446-2574 Sentence denotes For example, the study of MERS-CoV vaccines was accelerated by virtue of strategies that had been established for SARS-CoV [42].
T63 2575-2661 Sentence denotes It has been reported that the 2019-nCoV is also genetically close to SARS-CoV [43,44].
T64 2662-2926 Sentence denotes Therefore, to predict whether vaccines developed for SARS-CoV will also be effective against 2019-nCoV infection, the full length S protein sequences from the 2019-nCoV, a SARS-CoV, and two genetically similar bat CoV strains were selected for alignment (Fig. 1 ).
T65 2927-2987 Sentence denotes The results indicated more than 50% homology of the viruses.
T66 2988-3341 Sentence denotes However, the most variable residues are located in S1, a critical vaccine target, implying that neutralizing antibodies that were so effective against SARS-CoV infection may fail to recognize the 2019-nCoV, and that multiple amino acid differences at the receptor binding motif may modify virus tropism, a possible reason for cross-species transmission.
T67 3342-3400 Sentence denotes Fig. 1 Comparison of S protein sequences of coronaviruses.
T68 3401-3498 Sentence denotes Multiple alignment of full amino acid sequences of S protein from 2019-nCoV (GISAID accession no.
T69 3499-3547 Sentence denotes EPI_ISL_402124), SARS-CoV (GenBank accession no.
T70 3548-3596 Sentence denotes AY278489), bat-SL-CoVZC45 (GenBank accession no.
T71 3597-3652 Sentence denotes MG772933.1), and bat-SL-CoVZXC21 (GenBank accession no.
T72 3653-3837 Sentence denotes MG772934.1) was performed and displayed with clustalx1.83 and MEGA4 respectively. ‘‘-” represents the unconfirmed amino acid residues, “.” represents the identical amino acid residues.
T73 3838-4065 Sentence denotes The functional domains were labeled based on the research on SARS-CoV [41]; light blue box was for RBD region; dark blue box for receptor binding motif (RBM); light purple box for HR1; and dark purple box for HR2, respectively.
T74 4066-4232 Sentence denotes Double underlined regions in HR1 and HR2 are fusion cores, which are critical regions responsible for the formation of stable six-helical bundles between HR1 and HR2.
T75 4233-4329 Sentence denotes However, several bottlenecks typically delay the approval of vaccines to prevent CoVs infection.
T76 4330-4400 Sentence denotes First, a lack of proper animal models for evaluating vaccine efficacy.
T77 4401-4680 Sentence denotes Second, there are limitations from the S protein itself, such as mutations in the neutralization antibody epitopes in S protein that can cause virus escape [45], or non-neutralization antibody epitopes in vaccines that may elicit antibody-mediated disease enhancement (ADE) [46].
T78 4681-4734 Sentence denotes Third, DNA vaccines may recombine with other viruses.
T79 4735-4840 Sentence denotes Fourth, pre-existing immunity may eliminate the vaccine by removing the general human virus vectors [47].
T80 4841-4978 Sentence denotes Finally, there is the problem of return on investment which may be slow and, hence, inhibit investments and slow down the clinical study.
T81 4979-5236 Sentence denotes Jiang and colleagues have demonstrated that RBD in the SARS-CoV S protein is the major target of neutralizing antibodies in SARS patients and is able to induce highly potent neutralizing antibody responses and long-term protective immunity in animal models.
T82 5237-5407 Sentence denotes It contains 6 different conformational neutralizing epitopes, to which a series of mouse monoclonal antibodies (mAbs) with different neutralizing activity were generated.
T83 5408-5646 Sentence denotes Interestingly, these mAbs exhibited cross-neutralizing activities against divergent SARS-CoV strains isolated from SARS patients at different stages of SARS epidemics in 2002–2004 and those from palm civets [[48], [49], [50], [51], [52]].
T84 5647-5857 Sentence denotes This group has also shown that these SARS-CoV-RBD-specific neutralizing mAbs can cross-neutralize bat SL-CoVs, such as bat SL-CoV-W1V1 [53], indicating that these antibodies may also cross-neutralize 2019-nCoV.
T85 5858-6167 Sentence denotes Most importantly, RBD-based vaccine could induce neutralizing antibody responses and protection against SARS-CoV infection in the immunized animals, while it did not elicit ADE or other harmful immune responses, unlike the virus-inactivated vaccines or full-length S protein-based vaccines as discussed above.
T86 6168-6303 Sentence denotes Therefore, this RBD-based SARS vaccine is expected to be safer and more effective than the vaccines targeting other sites in S protein.
T87 6304-6581 Sentence denotes Jiang and Du’s groups have collaborated with Hotez’s group at Baylor College of Medicine in Houston and Tseng’s group at the University of Texas Medical Branch at Galveston, Texas, USA in development of an effective and safe vaccine at the late stage of preclinical study [54].
T88 6582-6684 Sentence denotes The antibodies induced by this vaccine candidate are expected to cross-neutralize 2019-nCoV infection.
T89 6685-6940 Sentence denotes If it is confirmed, this vaccine candidate has the great potential to be further developed promptly in clinical trials in both China and the United State through the continuous collaborations among the four groups of Drs. Hotez, Tseng, Du, and Jiang [55].