| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-131 |
Sentence |
denotes |
The antiviral compound remdesivir potently inhibits RNA-dependent RNA polymerase from Middle East respiratory syndrome coronavirus. |
| T2 |
132-369 |
Sentence |
denotes |
Antiviral drugs for managing infections with human coronaviruses are not yet approved, posing a serious challenge to current global efforts aimed at containing the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). |
| T3 |
370-552 |
Sentence |
denotes |
Remdesivir (RDV) is an investigational compound with a broad spectrum of antiviral activities against RNA viruses, including SARS-CoV and Middle East respiratory syndrome (MERS-CoV). |
| T4 |
553-631 |
Sentence |
denotes |
RDV is a nucleotide analog inhibitor of RNA-dependent RNA polymerases (RdRps). |
| T5 |
632-826 |
Sentence |
denotes |
Here, we co-expressed the MERS-CoV nonstructural proteins nsp5, nsp7, nsp8, and nsp12 (RdRp) in insect cells as a part a polyprotein to study the mechanism of inhibition of MERS-CoV RdRp by RDV. |
| T6 |
827-896 |
Sentence |
denotes |
We initially demonstrated that nsp8 and nsp12 form an active complex. |
| T7 |
897-987 |
Sentence |
denotes |
The triphosphate form of the inhibitor (RDV-TP) competes with its natural counterpart ATP. |
| T8 |
988-1167 |
Sentence |
denotes |
Of note, the selectivity value for RDV-TP obtained here with a steady-state approach suggests that it is more efficiently incorporated than ATP and two other nucleotide analogues. |
| T9 |
1168-1259 |
Sentence |
denotes |
Once incorporated at position i, the inhibitor caused RNA synthesis arrest at position i+3. |
| T10 |
1260-1331 |
Sentence |
denotes |
Hence, the likely mechanism of action is delayed RNA chain termination. |
| T11 |
1332-1445 |
Sentence |
denotes |
The additional three nucleotides may protect the inhibitor from excision by the viral 3'-5' exonuclease activity. |
| T12 |
1446-1551 |
Sentence |
denotes |
Together, these results help to explain the high potency of RDV against RNA viruses in cell-based assays. |