LitCovid-sentences  

PMC:7435837 / 6185-12165 JSONTXT 10 Projects

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Id Subject Object Predicate Lexical cue
T51 0-2 Sentence denotes 3.
T52 3-63 Sentence denotes Potential Targets for Drug Development against Coronaviruses
T53 64-195 Sentence denotes It has been shown at the time of writing that ACE-2 receptors in the lungs are specific targets for SARS-CoV-2 spike proteins [15].
T54 196-423 Sentence denotes It has been found that lung parenchyma must be in the differentiated state of the cell cycle and must express the ACE-2 receptor on the apical side, i.e., the site of the first contact with air, of the parenchyma [16,17,18,19].
T55 424-543 Sentence denotes It is no surprise therefore that the SARS, MERS, and SARS-CoV-2 viruses cause significant lung injury [20,21,22,23,24].
T56 544-755 Sentence denotes ACE-2 is also expressed to a significant extent in the gastrointestinal tract (GIT) [25] which accounts for the GIT symptoms that appeared in SARS-CoV patients and currently in SARS-CoV-2 infected patients [26].
T57 756-921 Sentence denotes Current pharmaceutical efforts against coronaviruses aim to interfere with the binding of the viral glycans in their spike proteins to potential host cell receptors.
T58 922-1079 Sentence denotes The drug umifenovir has been shown to prevent the fusion of viral S-proteins with the host cell ACE-2 receptors, therefore excluding cell entry of the virus.
T59 1080-1172 Sentence denotes However, umifenovir was clinically inefficient to improve the Covid-19 disease outcome [27].
T60 1173-1298 Sentence denotes A contributing membrane-bound enzyme that facilitates spike protein entry via ACE-2 receptors is the TMPRSS2 serine protease.
T61 1299-1479 Sentence denotes This protease primes the coronavirus spike protein for entry by cleaving protein domains that increase the interaction with host cell membranes that result in membrane fusion [28].
T62 1480-1621 Sentence denotes It was also suggested that TMPRSS2 cleaves ACE-2 sites that promote the affinity for the viral spike protein, hence enhances cell entry [29].
T63 1622-1776 Sentence denotes Another possible target for treatment is the inhibition of the synthesis of the required saccharides that are incorporated in the host cell glycoproteins.
T64 1777-1920 Sentence denotes Several quinine derivatives showed that these saccharide moieties known as sialic acids could be inhibited by drugs such as hydroxychloroquine.
T65 1921-2072 Sentence denotes The quinines, therefore, decrease the number of glycan targets that could be engaged by coronaviral spike proteins to facilitate cell entry [30,31,32].
T66 2073-2200 Sentence denotes However, quinine derivatives pose significant cardiotoxicity that precludes their application as a treatment for Covid-19 [33].
T67 2201-2336 Sentence denotes Antiretrovirals such as nelfinavir have proven to be efficient inhibitors of post-entry replication of the virions of SARS-CoV [34,35].
T68 2337-2545 Sentence denotes It has been found that protease inhibitors used in SARS and MERS studies prevented the cleavage and activation of spike proteins following the translation of precursor polypeptides from the viral RNA [36,37].
T69 2546-2643 Sentence denotes RNA is a vital step towards the ultimate formation of the structural protein of new viruses [34].
T70 2644-2794 Sentence denotes Ritonavir and lopinavir [38] have shown some good activity against the SARS-CoV protein cleavage that ultimately prevents spike proteins from forming.
T71 2795-2952 Sentence denotes Some investigated drugs have been reviewed as protease inhibitors against coronaviruses and the reader is referred to the publication by Adedeji et al. [39].
T72 2953-3034 Sentence denotes Figure 2 shows the currently identified targets for which drugs are investigated.
T73 3035-3134 Sentence denotes Vaccination efforts are attempting to create a substrate that can be recognized by dendritic cells.
T74 3135-3249 Sentence denotes The dendritic cells will subsequently label the virus spike proteins with coronavirus specific CD4+/CD8+ peptides.
T75 3250-3371 Sentence denotes These specifically loaded particles will then be presented to T-cells that interact with T-lymphocyte dependent antigens.
T76 3372-3564 Sentence denotes This interaction results in the induction of B-lymphocytes that produces antibodies that can recognize the spike proteins of coronaviruses to afford phagocytosis and destructions of the virus.
T77 3565-3762 Sentence denotes It is also expected that memory T-cells will form which could result in long-term immunity when these cells are replicated when a spike protein can be recognized by dendritic or other immune cells.
T78 3763-3901 Sentence denotes The carbohydrate-based vaccine holds promise to present recognizable glycan arrays that are representative of the targeted pathogens [41].
T79 3902-4115 Sentence denotes Very recently, several targets have been identified for the development of SARS-CoV-2 vaccines that have been identified based on the similarity of the virus to a previously encountered coronavirus, SARS-CoV [42].
T80 4116-4368 Sentence denotes It has been proven that many of the human pathogenic coronaviruses share a significant genomic overlap of more than 99.9% and this provides the basis for developing vaccines from a previously encountered coronavirus infection before SARS-CoV-2 [15,43].
T81 4369-4534 Sentence denotes The Middle East respiratory syndrome-related coronavirus, MERS-CoV, and SARS-CoV form part of these β-coronaviruses which wreaked havoc in the last two decades [44].
T82 4535-4692 Sentence denotes Therefore, one of the most promising targets is the characterization of spike protein epitopes that can be recognized by immune cells such as B- and T-cells.
T83 4693-4934 Sentence denotes Some form of replication of this spike protein epitope should, therefore, be developed and this will hopefully provide the antigens which can bind to, for example, B- or T-cell antibodies and alert the immune system to coronaviruses [44,45].
T84 4935-5082 Sentence denotes A recombinant vaccination approach could be demonstrated by expressing the receptor-binding domain [46] of SARS-CoV spike protein in an adenovirus.
T85 5083-5241 Sentence denotes This recombinant adenovirus was administered nasally and T-cells showed a significant immune response towards the expressed spike protein-binding domain [47].
T86 5242-5391 Sentence denotes Recombinant DNA approaches have made significant strides towards the synthesis of peptide sequences that can directly bind to spike protein epitopes.
T87 5392-5460 Sentence denotes Spike proteins of the MERS-CoV were neutralized in this way [48,49].
T88 5461-5580 Sentence denotes The spike protein antigen of the MERS-CoV was also reported and identified targets for spike protein deactivation [50].
T89 5581-5718 Sentence denotes It is emphasized that the discussion of chemotherapeutic and vaccination efforts is superficial and not covered in detail in this report.
T90 5719-5829 Sentence denotes Of importance though is the fact that antigen-antibody interactions are a key interest in developing vaccines.
T91 5830-5980 Sentence denotes This recognition mechanism is creating the prelude for the discussion of the layer-by-layer nanocoating process that will be elaborated in due course.