LitCovid-sentences  

PMC:7441777 / 40999-47823 JSONTXT 11 Projects

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Id Subject Object Predicate Lexical cue
T418 0-4 Sentence denotes 3.3.
T419 6-101 Sentence denotes Prediction of the absorption, distribution, metabolism, excretion, and toxicity (ADMET) profile
T420 102-392 Sentence denotes In addition to testing the physiochemical efficiency of a given molecule to inhibit the target protein, other parameters such as absorption, distribution, metabolism, excretion, and toxicity (ADMET) of the inhibitor play a critical role on demonstrating the likelihood of success of a drug.
T421 393-641 Sentence denotes Utilization of in-silico ADMET profiling, in combination with in vivo and in vitro predictions in the initial stage of the screening process, can significantly fasten the drug discovery process by minimizing the number of potential safety problems.
T422 642-885 Sentence denotes Hence, we performed a detailed ADMET profiling to evaluate the drug likeliness of the four polyphenols: EGCG, TF2a, TF2b, TF3 that exhibited the highest score from the MD simulation and MM-PBSA study along with the positive control remdesivir.
T423 886-1049 Sentence denotes Human colon adenocarcinoma-2 cell line (Caco2) permeability and human intestinal absorption (HIA) are key parameters to decide the total bioavailability of a drug.
T424 1050-1256 Sentence denotes All the five compounds (EGCG, TF2a, TF2b, TF3, and remdesivir) showed comparatively low Caco2 permeability potential (<8 × 10−6 cm/s) and could be absorbed via the human intestine (Larregieu & Benet, 2013).
T425 1257-1410 Sentence denotes EGCG, TF2a, TF2b, TF3, and remdesivir were predicted to be substrates of permeability glycoprotein (P-glycoprotein), which is an efflux membrane protein.
T426 1411-1593 Sentence denotes However, remdesivir was predicted as a P-glycoprotein I inhibitor, and EGCG and TF3 as a P-glycoprotein II inhibitor, whereas TF2a and TF2b as both P-glycoprotein I and II inhibitor.
T427 1594-1741 Sentence denotes Hence, above mentioned five compounds could regulate the physiological functions of P-glycoprotein (see Table S3 in the Supplementary Information).
T428 1742-1915 Sentence denotes The distribution of a drug is regulated by many parameters such as lipid-solubility, concentration in plasma and binding ability to plasma proteins, transport proteins, etc.
T429 1916-2095 Sentence denotes The volume of distribution at steady-state (VDss) suggests that EGCG, TF2a, TF2b, TF3, and remdesivir had a lower theoretical dose required for uniform distribution in the plasma.
T430 2096-2328 Sentence denotes Further, the degree of diffusion across the plasma membrane increases in the following order remdesivir < EGCG < TF2a < TF2b < TF3 (Table S4 in the Supplementary Information) as measured by the fraction that is in the unbound state.
T431 2329-2559 Sentence denotes The predictions through the distribution of the drugs via the central nervous system and blood-brain barrier suggest that these five compounds are poorly distributed to the brain and unable to penetrate the central nervous system.
T432 2560-2696 Sentence denotes However, the medium level of the lipophilicity of the drugs suggests that they would have no negative impact on nervous system exposure.
T433 2697-2767 Sentence denotes Cytochromes P450 (CYP) isozymes play crucial roles in drug metabolism.
T434 2768-2898 Sentence denotes It has been observed that TF2a, TF3, and remdesivir are a substrate of CYP3A4 and hence, can be efficiently metabolized by CYP3A4.
T435 2899-2989 Sentence denotes On the other hand, EGCG is a CYP3A4 inhibitor (Table S5 in the Supplementary Information).
T436 2990-3172 Sentence denotes On a separate note, EGCG is predominantly metabolized in the small intestine and liver by the conjugate formation of glucuronide, methyl sulfates in the urine and plasma (Chow et al.
T437 3173-3179 Sentence denotes 2005).
T438 3180-3357 Sentence denotes Among the five compounds, TF2b and TF3 were predicted as the substrate of renal organic cation transporter-2 (Renal OCT2), as shown in Table S6 in the Supplementary Information.
T439 3358-3482 Sentence denotes While EGCG, TF2a, and remdesivir are possibly cleared through other available routes such as bile, breath, faces, and sweat.
T440 3483-3581 Sentence denotes EGCG remains intact in the plasma and later excreted via bile and metabolized by colon microflora.
T441 3582-3662 Sentence denotes It is also expected that all the compounds are absorbable via oral prescription.
T442 3663-3769 Sentence denotes We have also analyzed the toxicity profiles for EGCG, TF2a, TF2b, TF3 as well as remdesivir (see Table 7).
T443 3770-3938 Sentence denotes The toxicity prediction from the AMES test (Salmonella typhimurium reverse mutation assay) exhibited that all the compounds could be considered as non-mutagenic agents.
T444 3939-4014 Sentence denotes High toxicity was observed for all the compounds in Tetrahymena pyriformis.
T445 4015-4125 Sentence denotes EGCG, TF2a, TF2b, TF3, and remdesivir were shown to inhibit the human ether-a-go-go-related gene II (hERG II).
T446 4126-4268 Sentence denotes However, Remdesivir has been shown to induce hepatotoxicity, whilst EGCG, TF2a, TF2b, TF3 are not likely to be associated with hepatotoxicity.
T447 4269-4450 Sentence denotes The maximum recommended tolerated dose (MRTD) in human prediction shows that remdesivir violate MRTD whereas natural polyphenol EGCG, TF2a, TF2b, TF3 do not fall into this category.
T448 4451-4605 Sentence denotes Remdesivir does not possess high acute toxicity whereas EGCG, TF2a, TF2b, and TF3 regarded as high acute toxic compound as it falls under minnow toxicity.
T449 4606-4693 Sentence denotes Additionally, none of the compounds predicted to be associated with skin sensitization.
T450 4694-4702 Sentence denotes Table 7.
T451 4704-4772 Sentence denotes Predicted toxicity profile of EGCG, TF3, TF2b, TF2a, and remdesivir.
T452 4773-4775 Sentence denotes S.
T453 4776-4779 Sentence denotes No.
T454 4781-4819 Sentence denotes Compounds name Toxicity prediction  
T455 4820-4854 Sentence denotes     Properties Predicted values
T456 4855-4881 Sentence denotes 1 EGCG AMES toxicity No
T457 4882-4941 Sentence denotes     Maximum tolerated dose (Human) 0.441 (log mg/kg/day)
T458 4942-4968 Sentence denotes     hERG I inhibitor No
T459 4969-4997 Sentence denotes     hERG II inhibitor Yes
T460 4998-5050 Sentence denotes     Oral rat acute toxicity (LD50) 2.522 (mol/kg)
T461 5051-5116 Sentence denotes     Oral rat chronic toxicity (LOAEL) 3.065 (log mg/kg_bw/day)
T462 5117-5141 Sentence denotes     Hepatotoxicity No
T463 5142-5168 Sentence denotes     Skin sensitivity No
T464 5169-5211 Sentence denotes     T. pyriformis toxicity 0.285 (µg/L)
T465 5212-5247 Sentence denotes     Minnow toxicity 7.713 log mM
T466 5248-5273 Sentence denotes 2 TF3 AMES toxicity No
T467 5274-5333 Sentence denotes     Maximum tolerated dose (Human) 0.438 (log mg/kg/day)
T468 5334-5360 Sentence denotes     hERG I inhibitor No
T469 5361-5389 Sentence denotes     hERG II inhibitor Yes
T470 5390-5442 Sentence denotes     Oral rat acute toxicity (LD50) 2.482 (mol/kg)
T471 5443-5508 Sentence denotes     Oral rat chronic toxicity (LOAEL) 7.443 (log mg/kg_bw/day)
T472 5509-5533 Sentence denotes     Hepatotoxicity No
T473 5534-5560 Sentence denotes     Skin sensitivity No
T474 5561-5603 Sentence denotes     T. pyriformis toxicity 0.285 (µg/L)
T475 5604-5639 Sentence denotes     Minnow toxicity 9.738 log mM
T476 5640-5666 Sentence denotes 3 TF2b AMES toxicity No
T477 5667-5726 Sentence denotes     Maximum tolerated dose (Human) 0.438 (log mg/kg/day)
T478 5727-5753 Sentence denotes     hERG I inhibitor No
T479 5754-5782 Sentence denotes     hERG II inhibitor Yes
T480 5783-5835 Sentence denotes     Oral rat acute toxicity (LD50) 2.482 (mol/kg)
T481 5836-5901 Sentence denotes     Oral rat chronic toxicity (LOAEL) 5.322 (log mg/kg_bw/day)
T482 5902-5926 Sentence denotes     Hepatotoxicity No
T483 5927-5953 Sentence denotes     Skin sensitivity No
T484 5954-5996 Sentence denotes     T. pyriformis toxicity 0.285 (µg/L)
T485 5997-6032 Sentence denotes     Minnow toxicity 8.685 log mM
T486 6033-6059 Sentence denotes 4 TF2a AMES toxicity No
T487 6060-6119 Sentence denotes     Maximum tolerated dose (Human) 0.439 (log mg/kg/day)
T488 6120-6146 Sentence denotes     hERG I inhibitor No
T489 6147-6175 Sentence denotes     hERG II inhibitor Yes
T490 6176-6228 Sentence denotes     Oral rat acute toxicity (LD50) 2.484 (mol/kg)
T491 6229-6294 Sentence denotes     Oral rat chronic toxicity (LOAEL) 5.035 (log mg/kg_bw/day)
T492 6295-6319 Sentence denotes     Hepatotoxicity No
T493 6320-6346 Sentence denotes     Skin sensitivity No
T494 6347-6389 Sentence denotes     T. pyriformis toxicity 0.285 (µg/L)
T495 6390-6425 Sentence denotes     Minnow toxicity 4.898 log mM
T496 6426-6458 Sentence denotes 5 Remdesivir AMES toxicity No
T497 6459-6517 Sentence denotes     Maximum tolerated dose (Human) 0.15 (log mg/kg/day)
T498 6518-6544 Sentence denotes     hERG I inhibitor No
T499 6545-6573 Sentence denotes     hERG II inhibitor Yes
T500 6574-6626 Sentence denotes     Oral rat acute toxicity (LD50) 2.043 (mol/kg)
T501 6627-6692 Sentence denotes     Oral rat chronic toxicity (LOAEL) 1.639 (log mg/kg_bw/day)
T502 6693-6718 Sentence denotes     Hepatotoxicity Yes
T503 6719-6745 Sentence denotes     Skin sensitivity No
T504 6746-6788 Sentence denotes     T. pyriformis toxicity 0.285 (µg/L)
T505 6789-6824 Sentence denotes     Minnow toxicity 0.291 log mM