| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T181 |
0-4 |
Sentence |
denotes |
2.7. |
| T182 |
5-11 |
Sentence |
denotes |
AT-527 |
| T183 |
12-236 |
Sentence |
denotes |
It is an investigational, orally active, purine nucleotide prodrug (Figure S3), which has exhibited antiviral activity against many single-stranded, enveloped RNA viruses, including human flaviviruses and coronaviruses [77]. |
| T184 |
237-281 |
Sentence |
denotes |
It is a potent inhibitor of viral RdRp [78]. |
| T185 |
282-424 |
Sentence |
denotes |
Following oral administration as hemi-sulfate salt, the drug gets converted to the monophosphate form via multiple metabolic activation steps. |
| T186 |
425-565 |
Sentence |
denotes |
The first step is catalyzed by the action of human carboxylesterase 1 (CES1) and/or cathepsin A (CatA) to produce the L-alanyl intermediate. |
| T187 |
566-731 |
Sentence |
denotes |
Spontaneous hydrolysis followed by histidine triad nucleotide-binding protein 1 (HINT1)-mediated hydrolysis results in the formation of the monophosphate metabolite. |
| T188 |
732-1038 |
Sentence |
denotes |
Then, the monophosphate is transformed to guanosine analog by adenosine deaminase like protein 1 (ADALP1) and further phosphorylated by guanylate kinase 1 (GUK1) and nucleoside diphosphate kinase (NDPK) to the pharmacologically active form of AT-527 diphosphate (also reported as AT-9010) (Figure S3) [78]. |
| T189 |
1039-1183 |
Sentence |
denotes |
The safety, pharmacokinetics, and antiviral activity of AT-527 was earlier established in HCV-infected subjects with and without cirrhosis [79]. |
| T190 |
1184-1390 |
Sentence |
denotes |
The drug is currently being evaluated in a phase 2 double-blind, randomized, placebo-controlled study to determine its efficacy and safety in patients with moderate COVID-19 symptoms (NCT04396106; n = 190). |
