Id |
Subject |
Object |
Predicate |
Lexical cue |
T209 |
0-4 |
Sentence |
denotes |
4.2. |
T210 |
5-89 |
Sentence |
denotes |
Evolutionary Acquisition of C4-O-Acetyl and C9-O-Acetyl SA Recognition by HE Enzymes |
T211 |
91-97 |
Sentence |
denotes |
4.2.1. |
T212 |
98-122 |
Sentence |
denotes |
C4-O-Acetyl Modification |
T213 |
123-237 |
Sentence |
denotes |
For example, in the horse, C4-O-acetyl modification of Neu5Ac (SA) occupies more than 50% of the total SA content. |
T214 |
238-312 |
Sentence |
denotes |
The C4-O-acetylated Neu5Ac, Neu4,5Ac2, inhibits the influenza A2 virus HA. |
T215 |
313-450 |
Sentence |
denotes |
De-acetylation reagents such as NaOH or NaIO4 treatment completely hemagglutinate Neu4,5Ac2 by elimination of the C4-O-acetyl group [33]. |
T216 |
451-588 |
Sentence |
denotes |
The C4-O-acetyl Neu5Ac species are found in various sources such as equine erythrocyte GM3, starfish A. rubens and fish [34,35,36,37,38]. |
T217 |
589-674 |
Sentence |
denotes |
C4-O-acetylated Neu5Ac facilitates the initial attachment of viruses to target cells. |
T218 |
675-844 |
Sentence |
denotes |
Like the influenza C virus, infectious salmon anemia virus (ISAV), a member of the Orthomyxoviridae family, contains HE and HEF proteins to mediate virus entry and exit. |
T219 |
845-998 |
Sentence |
denotes |
C4-O-Ac Neu5Ac is the major receptor determinant of ISAV in receptor binding and destruction [38], while the influenza C virus recognizes C9-O-Ac Neu5Ac. |
T220 |
999-1190 |
Sentence |
denotes |
The acetylesterase RDE of ISAV cleaves C4-O-Ac via 4-SA-O-acetylesterase with a short turnover time, whereas C9-O-Ac Neu5Ac is cleaved by 9-SA-O-acetylesterase with a long turnover time [34]. |
T221 |
1191-1330 |
Sentence |
denotes |
The position of SA O-acetylation is linked to functions including substrate differentiation of enzymes such as NAs and esterase by C4 O-Ac. |
T222 |
1331-1460 |
Sentence |
denotes |
Previous development of O-Ac site-selective NA inhibitors were based on the conceptual consideration of different O-Ac positions. |
T223 |
1461-1569 |
Sentence |
denotes |
The O-Ac of SAs is site-specific, as C4 of Neu5Ac is considered to be a potential position for modification. |
T224 |
1570-1678 |
Sentence |
denotes |
Historically, inhibitors of influenza A and B viruses-sialidases were designed by Von-Itzstein in 1993 [39]. |
T225 |
1679-1788 |
Sentence |
denotes |
The Ac group-based C4 substitution interacts with amino acid Glu-119 present in the active site of sialidase. |
T226 |
1789-1958 |
Sentence |
denotes |
Guanidine-attached C4 of C2–C3 unsaturated SA (Neu5Ac2en) inhibits activity of sialidases isolated from influenza A virus (Singapore/1/57) and B virus (Victoria/102/85). |
T227 |
1959-2093 |
Sentence |
denotes |
The same scenario was applied for sialidase inhibition of the human parainfluenza virus type 3, which has HN and fusion proteins [40]. |
T228 |
2094-2172 |
Sentence |
denotes |
The C4 of Neu5Ac2en was substituted by alkyl groups such as the O-ethyl group. |
T229 |
2173-2262 |
Sentence |
denotes |
For example, Zanamivir has a substitution with a 4-guanidino group with an IC50 of 25 μM. |
T230 |
2263-2336 |
Sentence |
denotes |
Thus, sialidase inhibition is important for C4 modification of Neu5Ac2en. |
T231 |
2337-2480 |
Sentence |
denotes |
Later, oseltamivir with the tradename Tamiflu (Basel, Switzerland) and zanamivir with the tradename Relenza (London, UK) were established [41]. |
T232 |
2481-2554 |
Sentence |
denotes |
These drugs exhibit some adverse side effects that restrict clinical use. |
T233 |
2556-2562 |
Sentence |
denotes |
4.2.2. |
T234 |
2563-2590 |
Sentence |
denotes |
SA C9-O-Acetyl Modification |
T235 |
2591-2769 |
Sentence |
denotes |
The SA 9-O-acetylation in hosts allows hosts to evade influenza A virus hemagglutinin (HA) recognition and some lectins of factor H (FH), CD22/Siglec-2 and sialoadhesin/Siglec-1. |
T236 |
2770-2899 |
Sentence |
denotes |
Instead, the influenza C virus HA recognizes the hosts. β-elimination and permethylation eliminate the 9-O-acetyl group from SAs. |
T237 |
2900-3142 |
Sentence |
denotes |
Chemical modification of the C-9 position of Neu5,9Ac2 generates a 9-N-acetyl analog, 9-acetamido-9-deoxy-N-acetylneuraminic acid (Neu5Ac9NAc), a mimic of Neu5,9Ac2 with influenza C virus-binding capacity, which is not cleaved by the HE [42]. |
T238 |
3143-3209 |
Sentence |
denotes |
SA O-acetylesterase regulates the presence of 7,9-O-Ac and 9-O-Ac. |
T239 |
3210-3296 |
Sentence |
denotes |
SA O-acetylation and deacetylation are involved in development, cancer and immunology. |
T240 |
3297-3363 |
Sentence |
denotes |
SA O-acetylation alters host lectin bindings such as siglecs [29]. |
T241 |
3364-3428 |
Sentence |
denotes |
The presence of 9-O-Ac can also reduce the activity of NAs [43]. |
T242 |
3429-3488 |
Sentence |
denotes |
SA modifications regulate pathogen binding or pathogen NAs. |
T243 |
3489-3547 |
Sentence |
denotes |
Influenza A/B/C/D viruses use SA as their entry receptors. |
T244 |
3548-3683 |
Sentence |
denotes |
Influenza A and B subtypes bind to SAs via HA and NA to allow endocytosis of the virus and fusion of the viral envelope with endosomes. |
T245 |
3684-3794 |
Sentence |
denotes |
In contrast, influenza C and D subtypes bear only one coated glycoprotein, termed the HE fusion protein (HEF). |
T246 |
3795-3825 |
Sentence |
denotes |
The HEF acts as the HA and NA. |
T247 |
3826-4013 |
Sentence |
denotes |
HEF recognizes 9-O-acetyl SA for entry into cells, while the esterase domain removes 9-O-acetyl-groups and liberates the virus from mucus and mis-assembled virus aggregates after budding. |
T248 |
4014-4109 |
Sentence |
denotes |
The 9-O-Ac on cells prevents the NA activity and HA binding of the influenza A type virus [44]. |