LitCovid-sentences  

PMC:7600245 / 1800-7674 JSONTXT 9 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T16 0-2 Sentence denotes 1.
T17 3-15 Sentence denotes Introduction
T18 16-298 Sentence denotes Over the last 20 years, humanity has dealt with three serious coronavirus infection outbreaks, namely severe acute respiratory syndrome coronavirus (SARS-CoV, 2002–2003) [1], Middle East respiratory syndrome coronavirus (MERS-CoV, 2012–2019) [2], and SARS-CoV-2, (2019-present) [3].
T19 299-559 Sentence denotes Although it appears that the fatality rates for the first two outbreaks are much higher (9.2% and 37%, respectively) than the ongoing pandemic (~3.3% as of 5 September 2020) [4,5], the ongoing infectious disease of SARS-CoV-2 appears to be far more contagious.
T20 560-728 Sentence denotes The ongoing outbreak, widely known as coronavirus disease of 2019 (COVID-19), was recognized by the World Health Organization as a global pandemic on 11 March 2020 [6].
T21 729-864 Sentence denotes As of 5 September 2020, there have been more than 26.7 million confirmed cases worldwide with more than 876 thousand global deaths [4].
T22 865-960 Sentence denotes Efforts are ongoing to deliver an effective vaccine to protect individuals against the disease.
T23 961-1111 Sentence denotes Likewise, potential therapeutics to prevent and/or treat the disease and its complications are being advanced to clinical trials all around the world.
T24 1112-1531 Sentence denotes In this direction, effective treatments for COVID-19 patients, particularly those who have the severe version of the disease and become critically ill needing hospitalization, intensive care unit (ICU) admission, and mechanical ventilation, appear to include antiviral drugs as well as anti-inflammatory drugs and anticoagulant drugs to also treat the associated cytokine storm [7] and coagulopathies [8], respectively.
T25 1532-1688 Sentence denotes Considering the current clinical guidelines, remdesivir has been recommended for the treatment of COVID-19 in hospitalized patients with severe disease [9].
T26 1689-1809 Sentence denotes Furthermore, favipiravir has been approved for the treatment of COVID-19 in the hospital settings in few countries [10].
T27 1810-1978 Sentence denotes Moreover, dexamethasone as an anti-inflammatory drug has also been recommended in patients with COVID-19 who require mechanical ventilation or supplemental oxygen [11].
T28 1979-2086 Sentence denotes Despite the above recommendations and/or approvals, the need for effective treatment remains largely unmet.
T29 2087-2215 Sentence denotes Therefore, a large number of potential therapeutics continue to be developed and others are being advanced into clinical trials.
T30 2216-2349 Sentence denotes We recently reviewed the chemical and mechanistic aspects of antiviral drugs that block the early phase of the virus life cycle [12].
T31 2350-2531 Sentence denotes In this article, we review the chemical structures and the mechanisms of action of potential antiviral therapeutics that block/inhibit the post-entry stages of the virus life cycle.
T32 2532-2604 Sentence denotes We only include those therapeutics that are listed in clinicatrials.gov.
T33 2605-2660 Sentence denotes They include both old drugs and new molecular entities.
T34 2661-2743 Sentence denotes Many of the potential therapeutics are small molecules and few are macromolecules.
T35 2744-2810 Sentence denotes Some of these therapeutics also possess anti-inflammatory effects.
T36 2812-2883 Sentence denotes The Life Cycle of SARS-COV-2 and Potential Targets for Drug Development
T37 2884-2977 Sentence denotes The life cycle of the virus includes early-stage events and later-stage events (Figure 1a,b).
T38 2978-3123 Sentence denotes In the first stage, the virus utilizes its spike (S) protein to bind to angiotensin converting enzyme 2 (ACE2) on the host cell membrane [13,14].
T39 3124-3388 Sentence denotes The virus enters the host cell after the spike S protein-ACE2 complex is proteolytically activated by transmembrane protease serine 2 (TMPRSS2) (see (b) in Figure 1), which eventually permits the virus-host cell fusion and the release of the viral RNA genome [15].
T40 3389-3488 Sentence denotes Alternatively, the bound virus spike S protein can also be proteolytically activated by furin [16].
T41 3489-3687 Sentence denotes Further processing is promoted by cathepsins in (endo)lysosomes to ultimately aid in the viral envelope fusion with the host membranes and the release of the viral genome (see (a) in Figure 1) [17].
T42 3688-3908 Sentence denotes The RNA genome of SARS-CoV-2 has more than 29,800 nucleotides which encode for about 29 proteins: nonstructural proteins (NSPs; 16 proteins), structural proteins (4 proteins), and accessory proteins (9 proteins) [18,19].
T43 3909-4089 Sentence denotes The structural proteins are spike S protein, envelope (E) and membrane (M) proteins which form the viral envelope, and nucleocapsid (N) protein which binds to the virus RNA genome.
T44 4090-4408 Sentence denotes In the post-entry phase of the virus life cycle (Figure 1), the NSPs domain is expressed as two polypeptides which, after processing, produce papain like protease (PLpro) (NSP3), main protease (Mpro) (also known as 3-chymotrypsin-like protease (3CLpro); NSP5) [20], and RNA-dependent RNA polymerase (RdRp; NSP12) [21].
T45 4409-4549 Sentence denotes Initial processing of the two polypeptides is promoted by host proteases, and then, is propagated by the action of the viral PLpro and Mpro.
T46 4550-4643 Sentence denotes The viral RdRp is also responsible for the replication and amplification of the viral genome.
T47 4644-4894 Sentence denotes The viral RNA and the N structural protein are biosynthesized in the host cell cytoplasm, whereas other viral structural proteins including S, M, and E are eventually biosynthesized in the endoplasmic reticulum and transported to the Golgi apparatus.
T48 4895-5066 Sentence denotes The viral RNA–N complex and S, M, and E proteins are then assembled in the endoplasmic reticulum–Golgi intermediate compartment (ERGIC) to produce a mature virus particle.
T49 5067-5216 Sentence denotes The mature virus is then released from the Golgi apparatus via a budding process and next from the host cells by exocytosis (Figure 1) [12,22,23,24].
T50 5217-5378 Sentence denotes Collectively, the goal of antiviral therapeutics is to inhibit one or more events in the life cycle of the virus in order to impede the propagation of infection.
T51 5379-5526 Sentence denotes Along these lines, any protein or event in the virus life cycle can be considered as a molecular target for anti-COVID-19 drug development efforts.
T52 5527-5695 Sentence denotes In this review, we describe the antiviral agents that are currently being tested in clinical trials to block and/or inhibit the advanced events of the virus life cycle.
T53 5696-5874 Sentence denotes Although the majority of the presented antiviral therapeutics target the viral polymerase or the viral proteases, few other therapeutics target other molecular targets (Table 1).