Id |
Subject |
Object |
Predicate |
Lexical cue |
T11 |
0-75 |
Sentence |
denotes |
The current pandemic COVID-19 is caused by a novel coronavirus, SARS-CoV-2. |
T12 |
76-238 |
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 |
239-422 |
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 |
423-482 |
Sentence |
denotes |
But researchers are trying to develop new therapeutics (3). |
T15 |
483-844 |
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 |
845-1114 |
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 |
1115-1480 |
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 |
1481-1651 |
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 |
1652-1912 |
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 |
1913-2187 |
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 |
2188-2408 |
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 |
2409-2613 |
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 |
2614-2719 |
Sentence |
denotes |
Moreover, it has also been imperative to note that this serine residue is conserved in all coronaviruses. |
T24 |
2720-2860 |
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 |
2861-3083 |
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 |
3084-3350 |
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 |
3351-3724 |
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. |