LitCovid-sentences  

PMC:7102556 / 14583-20490 JSONTXT 14 Projects

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Id Subject Object Predicate Lexical cue
T90 0-61 Sentence denotes 3 Research and development of therapeutics and prophylactics
T91 62-167 Sentence denotes At the present, no specific antiviral therapy has been approved for treatment of infection by human CoVs.
T92 168-376 Sentence denotes As development of vaccines and compounds for prevention and treatment of infection have been brought to priority status by WHO and governments [56], numerous drug studies have been done or are moving forward.
T93 377-594 Sentence denotes Some of them focus on the CoV fusion/entry process either by inhibition of S1 mediated virus attachment or by blocking of S2 mediated virus-cell membrane fusion, and some of them interfere with viral replication [57].
T94 596-628 Sentence denotes 3.1 CoV fusion/entry inhibitors
T95 629-833 Sentence denotes Based on the previous experience in developing the HIV-1 fusion inhibitor SJ-2176 [58], Jiang et al. discovered the first anti-SARS-CoV peptide (SC-1) from the HR2 domain of SARS-CoV S protein S2 subunit.
T96 834-990 Sentence denotes SC-1 could bind onto the HR1 domain to form a six-helical bundle (6-HB), blocking S protein-mediated membrane fusion and inhibiting SARS-CoV infection [59].
T97 991-1258 Sentence denotes When MERS-CoV was circulating in human populations in 2012, following similar mechanistic design, Jiang’s research group developed another peptide, designated HR2P, which was derived from the virus HR2 region as well and effectively inhibited MERS-CoV infection [60].
T98 1259-1381 Sentence denotes The further modified version of HR2P, HR2P-M2, presented even better anti-MERS-CoV activity and pharmaceutical properties.
T99 1382-1521 Sentence denotes Development of broad-spectrum pan-CoV fusion inhibitors would be an ideal way to cope with epidemics or pandemics caused by emerging HCoVs.
T100 1522-1671 Sentence denotes The conservative amino acid sequence of the HR1 region across different CoVs has the potential to be a target domain for development of an inhibitor.
T101 1672-1857 Sentence denotes Continuing to work on the HR1 and HR2 domains, Jiang’s group discovered that the peptide OC43-HR2P, derived from the HR2 domain of HCoV-OC43, broadly inhibited fusion by multiple HCoVs.
T102 1858-1938 Sentence denotes By optimization of this peptide, a pan-CoV fusion inhibitor, EK1, was generated.
T103 1939-2102 Sentence denotes It could form a stable six-helix bundle (6-HB) structure with HR1s and showed significantly improved fusion-inhibitory activity and pharmaceutical properties [61].
T104 2103-2324 Sentence denotes The alignment of S protein in Fig. 1 exhibited 100% identity at the HR2 domains between the 2019-nCoV and SARS-CoV; however, they found 7 amino acid changes in the fusion core of the HR1, located in the EK1 binding motif.
T105 2325-2563 Sentence denotes Fortunately, the substitutions were conservative replacements which would not dramatically disrupt the interactions between EK1 and HR1, meaning that EK1 would still have the potential to be an effective inhibitor for 2019-nCoV infection.
T106 2565-2612 Sentence denotes 3.2 CoV S-RBD-specific neutralizing antibodies
T107 2613-2696 Sentence denotes So far, most neutralizing antibodies recognize the RBD in the S protein S2 of CoVs.
T108 2697-2925 Sentence denotes Compared with the high mutation rate in the S1 protein, S2 is much more conservative, thereby decreasing the off-target risk caused by amino acid replacement [62], and also bypassing the special epitopes that may cause ADE [63].
T109 2926-3071 Sentence denotes This means that the cocktail of monoclonal antibodies binding to different epitopes of RBD would be more desirable for therapeutic purposes [64].
T110 3072-3212 Sentence denotes For treatment, the monoclonal antibodies are from a human source or are humanized antibodies, isolated or generated with various approaches.
T111 3213-3310 Sentence denotes For example, wild-type mice were immunized with soluble recombinant RBD containing the S protein.
T112 3311-3461 Sentence denotes Then mouse antibodies were humanized and isolated, or transgenic mice were directly immunized, to express human versions of the antibodies [50,65,66].
T113 3462-3628 Sentence denotes However, direct cloning of single B cells from human survivors, used in combination with the phage-display antibody library, could provide authentic human antibodies.
T114 3629-3792 Sentence denotes Until now, it should be noted that many neutralizing antibodies have been successfully discovered for treatment of SARS-CoV [67] and MERS-CoV infection [45,68,69].
T115 3793-3873 Sentence denotes These antibodies have all been described favorably in the literature [29,70,71].
T116 3874-4089 Sentence denotes A similar approach is known as single chain fragment variable (scFv) library screening, whereby the use of RBD as a bait protein allows some neutralizing antibodies to be screened out from non-immune humans [72,73].
T117 4090-4273 Sentence denotes Antibodies effective at inhibiting SARS-CoV infection should also have the potential for treatment of 2019-nCoV as well, as long as the binding motif in RBD shares the same sequences.
T118 4274-4391 Sentence denotes The new neutralizing monoclonal antibodies would also be isolated from the patients using the established techniques.
T119 4393-4424 Sentence denotes 3.3 CoV replication inhibitors
T120 4425-4529 Sentence denotes Similar to developing vaccines, drugs effective against other RNA viruses were also repurposed for CoVs.
T121 4530-4603 Sentence denotes Two major types of drugs being nucleoside analogues and immunomodulators.
T122 4604-4734 Sentence denotes So far, the most common therapies tried in patients with CoVs are ribavirin, lopinavir/ritonavir, IFN, or their combinations [74].
T123 4735-5081 Sentence denotes Despite the antiviral activity observed with in vitro studies, the clinical effect was not consistent [75], in that ribavirin does not prolong the survival of SARS-CoV patients [74,76], while lopinavir/ritonavir plus ribavirin seemed to improve clinical outcomes for SARS patients [77], but the improvement was not confirmed in MERS-CoV patients.
T124 5082-5248 Sentence denotes IFNs showed effective at inducing antiviral activity against both SARS-CoV and MRES-CoV, but without significant improvement in the outcomes for the patients [78,79].
T125 5249-5415 Sentence denotes In addition to the drug regimens used in patients, numerous drugs developed for the treatment of infection with CoVs were thoroughly discussed in the literature [57].
T126 5416-5516 Sentence denotes However, replication of an RNA virus usually generates progeny viruses with a highly diverse genome.
T127 5517-5689 Sentence denotes Recombination also easily takes place between viral genomes [80], and these gene level changes may result in drug resistance if the mutations affect the drug target domain.
T128 5690-5907 Sentence denotes Development of drugs is also hampered by various evaluation methods and animal models used for testing drug activity among different labs worldwide, which could postpone selection of the best drug for clinical trials.