LitCovid-sentences  

PMC:7200337 / 70540-78559 JSONTXT 11 Projects

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Id Subject Object Predicate Lexical cue
T392 0-10 Sentence denotes Antivirals
T393 11-125 Sentence denotes Antivirals are a class of small molecules that function as inhibitors of one or more stages of a virus life cycle.
T394 126-265 Sentence denotes Because of similarities between different virus replication mechanisms, some antivirals can be repurposed against various viral infections.
T395 266-441 Sentence denotes Currently, most of the available antiviral drugs tested against SARS-CoV-2 are small molecules previously developed against SARS-CoV-1, MERS-CoV, or other RNA and DNA viruses.
T396 443-468 Sentence denotes Broad-Spectrum Antivirals
T397 469-615 Sentence denotes A number of small molecules with known antiviral activity against other human RNA viruses are being evaluated for efficacy in treating SARS-CoV-2.
T398 616-807 Sentence denotes The ribonucleoside analog β-D-N4-hydroxycytidine (NHC) reduced viral titers and lung injury in mice infected with SARS-CoV-2 via introduction of mutations in viral RNA (Sheahan et al., 2017).
T399 808-1034 Sentence denotes Further, an inhibitor of host DHODH, a rate-limiting enzyme in pyrimidine synthesis, was able to inhibit SARS-CoV-2 growth in vitro with greater efficacy than remdesivir or chloroquine (Wang et al., 2020e, Xiong et al., 2020).
T400 1035-1256 Sentence denotes Merimepodib, a non-competitive inhibitor of the enzyme inosine-5′-monophosphate dehydrogenase (IMPDH), involved in host guanosine biosynthesis, is able to suppress SARS-CoV-2 replication in vitro (Bukreyeva et al., 2020).
T401 1257-1554 Sentence denotes Finally, N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC), which was previously shown to efficiently reduce infection by the less-pathogenic human CoV HCoV-NL63, was also found to inhibit MERS-CoV and pseudotyped SARS-CoV-2 in human airway epithelial cells (Milewska et al., 2020).
T402 1556-1575 Sentence denotes Protease Inhibitors
T403 1576-1720 Sentence denotes Much of the antiviral computational and experimental data currently available for SARS-CoV-2 focus on targeting the 3CL or Main protease (Mpro).
T404 1721-1880 Sentence denotes Two prominent drug candidates targeting the SARS-CoV-2 Mpro were designed and synthesized by analyzing the substrate binding pocket of Mpro (Dai et al., 2020).
T405 1881-1989 Sentence denotes The X-ray crystal structures of the novel inhibitors in complex with SARS-CoV-2 Mpro were resolved at 1.5 Å.
T406 1990-2114 Sentence denotes Both compounds showed good pharmacokinetic activity in vitro, and one exhibited limited toxicity in vivo (Dai et al., 2020).
T407 2115-2204 Sentence denotes Multiple studies also aimed to repurpose protease inhibitors to reduce SARS-CoV-2 titers.
T408 2205-2527 Sentence denotes Nine existing HIV protease inhibitors (nelfinavir, lopinavir, ritonavir, saquinavir, atazanavir, tipranavir, amprenavir, darunavir, and indinavir) were evaluated for their antiviral activity in Vero cells infected with SARS-CoV-2 (Yamamoto et al., 2020), and nelfinavir was the most potent at inhibiting viral replication.
T409 2529-2544 Sentence denotes RdRp Inhibitors
T410 2545-2733 Sentence denotes The CoV RNA-dependent RNA polymerase (RdRp) catalyzes the synthesis of viral RNA (Gao et al., 2020a), making it essential for viral replication and a prime target for antiviral inhibitors.
T411 2734-2957 Sentence denotes Remdesivir, an adenosine triphosphate analog, inhibits RdRp by binding to RNA strands and preventing additional nucleotides from being added, thereby terminating viral RNA transcription (Figure 6 A) (Agostini et al., 2018).
T412 2958-3115 Sentence denotes Remdesivir has been previously shown to be effective against MERS-CoV and SARS-CoV-1 infections in animal models (Sheahan et al., 2017, de Wit et al., 2020).
T413 3116-3261 Sentence denotes Similarly, a study investigated the efficacy of remdesivir treatments on 12 rhesus macaques with SARS-CoV-2 infections (Williamson et al., 2020).
T414 3262-3392 Sentence denotes Macaques treated with remdesivir showed a reduction in lung viral loads and pneumonia symptoms but no reduction in virus shedding.
T415 3393-3523 Sentence denotes This study does provide evidence that if administered early enough, remdesivir may be effective at treating SARS-CoV-2 infections.
T416 3524-3628 Sentence denotes Figure 6 Available Therapeutic Options to Manage COVID-19 Immunopathology and to Deter Viral Propagation
T417 3629-3843 Sentence denotes (A) Rdrp inhibitors (remdesivir, favipiravir), protease inhibitors (lopinavir/ritonavir), and antifusion inhibitors (arbidol) are currently being investigated in their efficacy in controlling SARS-CoV-2 infections.
T418 3844-3951 Sentence denotes (B) CQ and HCQ increase the pH within lysosomes, impairing viral transit through the endolysosomal pathway.
T419 3952-4100 Sentence denotes Reduced proteolytic function within lysosomes augments antigen processing for presentation on MHC complexes and increases CTLA4 expression on Tregs.
T420 4101-4236 Sentence denotes (C) Antagonism of IL-6 signaling pathway and of other cytokine-/chemokine-associated targets has been proposed to control COVID-19 CRS.
T421 4237-4357 Sentence denotes These include secreted factors like GM-CSF that contribute to the recruitment of inflammatory monocytes and macrophages.
T422 4358-4574 Sentence denotes (D) Several potential sources of SARS-CoV-2 neutralizing antibodies are currently under investigation, including monoclonal antibodies, polyclonal antibodies, and convalescent plasma from recovered COVID-19 patients.
T423 4575-4710 Sentence denotes GM-CSF, granulocyte-macrophage colony-stimulating factor; CQ, chloroquine; HCQ, hydroxychloroquine; RdRp, RNA-dependent RNA polymerase.
T424 4712-4737 Sentence denotes Antiviral Clinical Trials
T425 4738-4830 Sentence denotes A large number of clinical trials using experimental antiviral drugs are currently underway.
T426 4831-5192 Sentence denotes A small proportion of them are aimed at repurposing existing antivirals, including arbidol (umifenovir), a broad-spectrum antiviral that blocks viral fusion; lopinavir/ritonavir (LPV/r), a combination of anti-HIV protease inhibitors; favipiravir, an RdRp inhibitor used to treat severe influenza infections (Hayden and Shindo, 2019); and remdesivir (Figure 6A).
T427 5193-5358 Sentence denotes Chen et al. conducted a multicenter, randomized priority trial on 240 patients with confirmed COVID-19 infection to test favipiravir or arbidol (Chen et al., 2020b).
T428 5359-5425 Sentence denotes Favipiravir was suggested to significantly improve symptom relief.
T429 5426-5608 Sentence denotes However, the interpretation of this study is limited by a short clinical recovery window of 7 days, only 100 of 236 patients with confirmed COVID-19, and the lack of a control group.
T430 5609-5752 Sentence denotes LPV/r has previously shown efficacy in treating SARS-Cov-1 (Chu et al., 2004), prompting an early SARS-Cov-2 clinical trial (Li et al., 2020c).
T431 5753-5936 Sentence denotes 44 patients were enrolled in a trial investigating the efficacy and safety of LPV/r (n = 21 patients), arbidol (n = 16), or control (n = 7) as treatment for mild to moderate COVID-19.
T432 5937-6140 Sentence denotes At day 14 of treatment, 76.2%, 62.4%, and 71.4% of patients had a positive to negative conversion in the LPV/r, arbidol, and control groups, respectively, with no statistical significance between groups.
T433 6141-6285 Sentence denotes A randomized controlled trial (RCT) with 200 severe COVID-19 patients did not observe a significant benefit of LPV/r either (Cao et al., 2020a).
T434 6286-6505 Sentence denotes However, a study that looked at the impact of earlier administration of LPV/r treatment showed that when treatment of LPV/r was started within 10 days of symptom onset, a shorter duration of virus shedding was observed.
T435 6506-6595 Sentence denotes Thus, timing of LPV/r administration may be critical to its efficacy (Yan et al., 2020a).
T436 6596-6802 Sentence denotes In a multicenter clinical study assessing the compassionate use of remdesivir in severe COVID-19 patients, 53 patients across several countries were treated with remdesivir for 10 days (Grein et al., 2020).
T437 6803-6934 Sentence denotes 68% of the 53 patients who received remdesivir showed clinical improvement assessed through improved oxygen support or extubations.
T438 6935-7059 Sentence denotes Without a proper control group, limited conclusions can be drawn with regards to the efficacy of remdesivir from this study.
T439 7060-7212 Sentence denotes The measured 68% clinical improvement may be in line with average clinical improvement across patients treated with standard of care (Li et al., 2020c).
T440 7213-7401 Sentence denotes A small RCT in China with 237 severe COVID-19 patients randomized 2:1 to remdesivir versus placebo demonstrated no significant benefit in time to clinical improvement (Wang et al., 2020g).
T441 7402-7633 Sentence denotes Almost simultaneously, preliminary results from a larger National Institute of Allergy and Infectious Diseases (NIAID) RCT with more than 1,000 patients were announced with remdesevir to be associated with quicker time to recovery:
T442 7634-7680 Sentence denotes 11 days compared with 15 days (Ledford, 2020).
T443 7681-7817 Sentence denotes A non-significant benefit in mortality was also noted, and the trial was stopped early to allow access to remdesivir in the placebo arm.
T444 7818-8019 Sentence denotes Complete safety data and full publication are awaited, but this study offers encouraging results and has resulted in an FDA emergency use authorization for remdesivir in hospitalized COVID-19 patients.