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PMC:7214327 JSONTXT 18 Projects

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Id Subject Object Predicate Lexical cue
T1 0-73 Sentence denotes Probable Molecular Mechanism of Remdesivir for the Treatment of COVID-19:
T2 74-91 Sentence denotes Need to Know More
T3 93-101 Sentence denotes Abstract
T4 102-148 Sentence denotes COVID-19 is now pandemic throughout the world.
T5 149-221 Sentence denotes Scientist, doctors are searching for effective therapy of this diseases.
T6 222-325 Sentence denotes The remdesivir, an antiviral drug, is appeared as ‘molecule of hope’ for the treatment of this disease.
T7 326-399 Sentence denotes USFDA gave emergency approval to this drug for the treatment of COVID-19.
T8 400-435 Sentence denotes The molecular mechanism is unknown.
T9 436-562 Sentence denotes In this paper, we tried to describe the probable molecular mechanism of remdesivir to inhibit the RNA synthesis of SARS-CoV-2.
T10 563-652 Sentence denotes However, more detail mechanism is needed to understand mechanism of action of remdesivir.
T11 654-729 Sentence denotes The current pandemic COVID-19 is caused by a novel coronavirus, SARS-CoV-2.
T12 730-892 Sentence denotes The disease is highly infectious like other coronaviral disease and causing already more than 2.3 lacs deaths worldwide, posing a serious threat to mankind (1,2).
T13 893-1076 Sentence denotes Scientists, doctors and other health professional are working very hard to combat this current situation, but still there is no drug or vaccine available to treat this morbid disease.
T14 1077-1136 Sentence denotes But researchers are trying to develop new therapeutics (3).
T15 1137-1498 Sentence denotes However this situation initiates a global effort to find out effective measures or discovery of new drugs or vaccines to stop the spreading of this deadly virus, but, since the development of a new vaccine or drug is a time-consuming process, repurposing of existing drug could be act as a brilliant alternative with potential to combat the disease effectively.
T16 1499-1768 Sentence denotes One of these drugs is remdesivir (RDV), which shows a broad spectrum of anti-viral activity against many viruses like Ebola (4,5), Nipah (6, 7, 8), respiratory syncytial virus (RSV) family (8) and a diverse category of coronaviruses including SARS CoV and MERS CoV (9).
T17 1769-2134 Sentence denotes Remdesivir is a nucleotide analogue (4), and the triphosphate form of RDV, i.e., RDV-TP is being used as a substrate for many viral RNA-dependent RNA polymerase (RdRp) complexes and it has been reported to inhibit the viral RNA synthesis by a specific mechanism of delayed chain termination for all three coronaviruses (MERS-CoV, SARS-CoV and SARS-CoV-2) RdRp (10).
T18 2135-2305 Sentence denotes It has been observed that RDV-TP resembles specifically Adenosine triphosphate (ATP) molecule and competes with the nucleotide during the viral RNA synthesis (Figure 1 ).
T19 2306-2566 Sentence denotes It has been reported that 3′ hydroxyl group of RDV-TP forms a phosphodiester bond with the next nucleotide but it terminates the formation of viral RNA synthesis at 3 nucleotides downstream, precisely at i + 3 position, whereas the RDV-TP is the i-th position.
T20 2567-2841 Sentence denotes Moreover, it has also been fascinating to note that the underlying mechanism of chain termination is more or less common in many viruses including all the recent coronaviruses, namely MERS-CoV, SARS-CoV and SARS-CoV-2, though the precise molecular mechanism remains elusive.
T21 2842-3062 Sentence denotes Additionally, it has been reported very recently that the main reason of chain termination at i + 4 position is due to a steric clash between 1′-CN substituent of the incorporated RDV-TP and a specific residue S861 (10).
T22 3063-3267 Sentence denotes It is consistent with the chain termination at i + 3 position due to the imposed inability of RdRp to translocate a single position downstream, so eventually it terminates the nascent viral RNA synthesis.
T23 3268-3373 Sentence denotes Moreover, it has also been imperative to note that this serine residue is conserved in all coronaviruses.
T24 3374-3514 Sentence denotes Though, the actual molecular mechanism is still not very clear but this could be a plausible explanation of termination viral RNA synthesis.
T25 3515-3737 Sentence denotes Recently, scientists also expressed RdRp of different viruses and measure kinetic parameters to infer its interaction with RDV-TP and also determined a score of 0.77 mmol half maximal concentration against SARS-CoV-2 (11).
T26 3738-4004 Sentence denotes Figure 1 Probable molecular mechanism of Remdisivir against SARS-CoV- 2. (A) Thematic diagram shows the SARS-CoV-2 viral entry and its RNA synthesis which can be block by Remdisivir. (B) Detail molecular mechanism of Remdisivir to inhibit the synthesis of viral RNA.
T27 4005-4378 Sentence denotes It can be concluded that this chain termination method could be a general mechanism of anti-viral activity of this particular substrate to a broad spectrum of different viral infection, but still the availability of human trial and safety data is pending, and also a detailed anti-viral profiling of this compound in cell culture study is highly appreciated at this moment.
T28 4380-4400 Sentence denotes Conflict of Interest
T29 4401-4459 Sentence denotes No potential conflict of interest was declared by authors.
T30 4461-4468 Sentence denotes Funding
T31 4469-4689 Sentence denotes This research was supported by Hallym University Research Fund and by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2017R1A2B4012944).
T32 4691-4709 Sentence denotes Supplementary data
T33 4710-4722 Sentence denotes Data Profile