LitCovid-sentences  

PMC:7712180 / 65993-75979 JSONTXT 3 Projects

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Id Subject Object Predicate Lexical cue
T342 0-6 Sentence denotes 4.3.4.
T343 7-81 Sentence denotes Receptor Binding Specificity of α HCoV-NL63, β2 SARS-CoV and β2 SARS-CoV-2
T344 82-392 Sentence denotes Results obtained by direct biochemical methods and X-ray crystallographic studies showed that α HCoV-NL63 [84,232], β2 SARS-CoV [233] and β2 SARS-CoV-2 [195] use their S1-CTD RBD to bind to a host receptor, angiotensin-converting enzyme 2 (ACE2, a zinc peptidase), that is essential for virus entry into cells.
T345 393-563 Sentence denotes As shown in Figure 4b, ACE2 is a homodimeric type I transmembrane protein having an orientation with the N-terminus outside and the C-terminus inside the cytoplasm [195].
T346 564-696 Sentence denotes The virus-binding site (VBS) of these three CoVs is not the peptidase active site but the outer surface of the ACE2 N-terminal lobe.
T347 697-761 Sentence denotes Analyses of cocrystal structures between RBDs of HCoV-NL63 (pdb:
T348 762-789 Sentence denotes 3kbh [232]), SARS-CoV (pdb:
T349 790-821 Sentence denotes 2ajf [234]) or SARS-CoV-2 (pdb:
T350 822-1115 Sentence denotes 6m0j [235]) and the human ACE2 (hACE2) receptor indicated aa residues covering the CoV–ACE2 interfaces, divided into a common region of hACE2 recognized by all three ACE2-recognizing CoVs (a hotspot region) and unique regions bound by HCoV-NL63, SARS-CoV or SARS-CoV-2 (Figure 4b, middle row).
T351 1116-1466 Sentence denotes Evidence indicating that HCoV-NL63 and SARS-CoV bind to the same hotspot region on hACE2 and that their binding is important for infection was obtained from infection inhibition studies showing that the SARS-CoV RBD can inhibit lentivirus infections mediated by the S protein of either SARS-CoV or HCoV-NL63 into hACE2-expressing HEK293T cells [236].
T352 1467-1663 Sentence denotes Likewise, the use of the HCoV-NL63 RBD as a competitive inhibitor can inhibit infections of murine leukemia viruses (MLVs) mediated by SARS-CoV S protein into hACE2-expressing HEK293T cells [237].
T353 1664-1945 Sentence denotes In addition, aa changes in the hotspot region in hACE2, either L353A or D38A substitution, resulted in a significant reduction of binding interactions between the SARS-CoV or HCoV-NL63 RBD and hACE2 and reduction of MLV infections mediated by SARS-CoV or HCoV-NL63 S protein [237].
T354 1946-2099 Sentence denotes The results of these studies suggested that the hotspot region on the hACE2 VBS is a potential target for development of drugs against ACE2-binding CoVs.
T355 2100-2357 Sentence denotes It should be noted that MLN-4760, an ACE2 inhibitor that binds to the ACE2 catalytic center and induces hACE2 conformational changes, did not affect interactions of SARS-CoV S1 with the hACE2 surface and did not affect SARS-CoV S protein-mediated infection.
T356 2358-2446 Sentence denotes Likewise, binding of SARS-CoV S1 to hACE2 did not affect hACE2 catalytic activity [238].
T357 2447-2587 Sentence denotes The aa sequences of hACE2 were aligned with aa sequences of ACE2 orthologues of possible natural reservoirs and possible intermediate hosts.
T358 2588-2670 Sentence denotes Only the aa sequences corresponding to the hACE2 interface are shown in Figure 4b.
T359 2671-2817 Sentence denotes Adaptation of each zoonotic virus to interact with aa residues at the hACE2 binding interface is critical for efficient transmission among humans.
T360 2818-3086 Sentence denotes The hACE2 residues K31, D38, Y41 and K353 are important host determinants of adaptation of civet SARSr-CoV to human SARS-CoV (Figure 4b), and viral S1 RBD residues at the positions of 479 and 487 are important determinants of SARS-CoV binding preference (Figure 8a–c).
T361 3087-3174 Sentence denotes The K479N mutation from civet to human viral S1 RBD can accommodate K31 on hACE2 [238].
T362 3175-3361 Sentence denotes The S487T mutation from civet to human viral S1 RBD can accommodate a hydrophobic pocket between Y41 and K353, neutralized by D38, on the hACE2 receptor for efficient interactions [234].
T363 3362-3604 Sentence denotes These findings agree with results obtained by Kan et al. [100] suggesting that viruses with SNVs leading to aa changes at these two positions are able to be transmitted from animals to infect humans and from humans to humans by close contact.
T364 3605-3880 Sentence denotes However, the roles of the additional 4 aa substitutions at position 344 in the RBD but outside the RBS (Figure 8b) and positions 227, 244 and 778 outside the RBD in viruses isolated from patients during the global epidemic [100] in human-to-human transmission remain unknown.
T365 3881-4009 Sentence denotes Crystal structure analysis indicated that the SARS-CoV-2 RBD to which hACE2 binds is almost identical to the SARS-CoV RBD [235].
T366 4010-4214 Sentence denotes Later, hACE2 amino acids at or near the RBD/ACE2 interface (Figure 4b) that could affect RBD/ACE2 binding were used for screening the capability of ACE2 of various animals used by SARS-CoV and SARS-CoV-2.
T367 4215-4692 Sentence denotes ACE2 of possible SARS-CoV and SARS-CoV-2 intermediate hosts, masked palm civet and Malayan pangolin, respectively, and ACE2 of many mammals including cats, dogs, cows, buffalos, goats and sheep, but not rats (Rattus norvegicus), were predicted to be potentially recognized by SARS-CoV and SARS-CoV-2 [239,240], supporting the finding that rat ACE2 has less efficiency for binding to the SARS-CoV S1 domain and is less susceptible to SARS-CoV S protein-mediated infection [241].
T368 4693-4845 Sentence denotes However, young female Fischer 344 (F344) rats of 4 weeks of age were shown to be susceptible to infection with SARS-CoV by intranasal inoculation [242].
T369 4846-4974 Sentence denotes Western blot analysis showed that ACE2 expression in Sprague Dawley rats decreased with aging without a gender difference [243].
T370 4975-5173 Sentence denotes However, it remains unknown whether there is a difference in ACE2 sequence depending on the age of rats and whether there are differences in ACE2 expression and sequence depending on the rat strain.
T371 5174-5327 Sentence denotes Based on ACE2 residues 31, 35, 38, 82 and 353, Chinese horseshoe bats, which are thought to be a natural reservoir, can be divided into two groups [240].
T372 5328-5494 Sentence denotes First, bat ACE2 of SARSr-CoV–RT-PCR-positive R. ferrumequinum (bat Rf) [220] was predicted not to have the ability to bind to either SARS-CoV-2 or SARS-CoV S protein.
T373 5495-5714 Sentence denotes Second, bat ACE2 of SARSr-CoV–seropositive and –RT-PCR-positive R. pearsonii, R. macrotis [220], and SARSr-CoV–RT-PCR-positive R. sinicus [95] was predicted to be able to bind to both SARS-CoV-2 and SARS-CoV S proteins.
T374 5715-5859 Sentence denotes Based on residues 20, 31, 41, 68, 83, 353, 355, 357 and 383, R. sinicus ACE2 was confirmed to have the potential to be used by SARS-CoV-2 [239].
T375 5860-6175 Sentence denotes These findings indicate the possibility of cross-species transmission of the virus from humans to animals carrying similar host receptor sequences, although other host factors, such as target organ temperature and cellular proteins interacting with the virus, may be involved in host range restriction of the virus.
T376 6176-6268 Sentence denotes Thus, surveillance of transmission both back and forth between humans and animals is needed.
T377 6269-6379 Sentence denotes The susceptible host range of HCoV-NL63, which causes mild respiratory disease [244], has not been determined.
T378 6380-6557 Sentence denotes However, the host range of HCoV-NL63 might be similar to that of SARS-CoV and SARS-CoV-2, and thus a mixed infection of these different viruses to the same host cells may occur.
T379 6558-6877 Sentence denotes Although α HCoV-NL63, β2 SARS-CoV and β2 SARS-CoV-2 recognize the same ACE2 receptor and all bind to the hotspot region on ACE2 (Figure 4b, middle), they have aa differences in the RBS at the viral RBD interface (Figure 8a), suggesting that they have undergone convergent evolution for efficient ACE2 binding [232,235].
T380 6878-7038 Sentence denotes While SARS-CoV and SARS-CoV-2 have similar RBD structures with a concave surface, α HCoV-NL63 has no structural RBD homology to βCoV RBDs (Figure 8b) [232,235].
T381 7039-7116 Sentence denotes Thus, we superimposed hACE2 receptors (green) in complex with HCoV-NL63 (pdb:
T382 7117-7138 Sentence denotes 3kbh), SARS-CoV (pdb:
T383 7139-7165 Sentence denotes 2ajf) and SARS-CoV-2 (pdb:
T384 7166-7194 Sentence denotes 6m0j) as shown in Figure 8b.
T385 7195-7374 Sentence denotes However, since all three viruses interact with the same hotspot region on the hACE2 receptor, RBS residues of these different viruses occupy similar positions in the hotspot area.
T386 7375-7596 Sentence denotes For example, S535/T487/N501 of HCoV-NL63/SARS-CoV/SARS-CoV-2 are located near K353 and Y41 of hACE2, while Y498/Y491/Y505 of HCoV-NL63/SARS-CoV/SARS-CoV-2 are located near K353, E37 and D38 of hACE2 (Figure 8c) [235,237].
T387 7597-7920 Sentence denotes By using surface plasmon resonance with a Biacore 2000/3000 instrument, equilibrium dissociation constant (Kd, smaller value indicating greater binding affinity) values between HCoV-NL63 RBD and immobilized hACE2 and between SARS-CoV RBD and immobilized hACE2 were determined to be 34.9 and 20.8 nM, respectively [232,237].
T388 7921-8303 Sentence denotes It should be noted that NL63-CoV RBD-hACE2 interactions have lower koff and kon values than do SARS-CoV RBD-hACE2 interactions, suggesting that NL63-CoV RBD/hACE2 complex has less electrostatic and more hydrophobic interactions [237]; three hydrogen bonds were observed in HCoV-NL63 RBD-hACE2 complex, but nine hydrogen bonds were observed in SARS-CoV RBD-hACE2 complex (Figure 8c).
T389 8304-8509 Sentence denotes By surface plasmon resonance with a Biacore T200 instrument, the Kd values of SARS-CoV RBD-immobilized hACE2 and SARS-CoV-2 RBD-immobilized hACE2 were determined to be 31 nM and 4.7 nM, respectively [235].
T390 8510-8640 Sentence denotes As mentioned earlier, S487T and K479N substitutions in the civet SARSr-CoV RBS are critical for civet-to-human transmission [238].
T391 8641-8746 Sentence denotes It appears that both T487 and N479 are substituted by N501 and Q493, respectively, in the SARS-CoV-2 RBS.
T392 8747-8864 Sentence denotes N501 in the SARS-CoV RBD and T486, but not T487, in the SARS-CoV RBD (Figure 8c) form a hydrogen bond with hACE2 Y41.
T393 8865-9076 Sentence denotes It is likely that subtle differences between the SARS-CoV RBD and SARS-CoV-2 RBD in interactions with hACE2 are responsible for the difference in Kd values of the SARS-CoV RBD and SARS-CoV-2 RBD for hACE2 [235].
T394 9077-9247 Sentence denotes For example, while N479 in the SARS-CoV RBD does not cause hydrogen bond formation, its substituted Q493 in the SARS-CoV-2 RBD makes two hydrogen bonds with E35 of hACE2.
T395 9248-9430 Sentence denotes K417 in the SARS-CoV-2 RBD provides a unique interaction with huACE2 D30 and a positive charged patch on the SARS-CoV-2 RBD, which is not found on the SARS-CoV RBD (Figure 8c) [235].
T396 9431-9563 Sentence denotes A virus with a great binding affinity, which can trigger infection efficiently, could be a factor of the rapid spread of SARS-CoV-2.
T397 9564-9635 Sentence denotes Other factors may be involved in driving the rapid spread of the virus.
T398 9636-9986 Sentence denotes For example, the presence of a polybasic (RRAR) site at the S1/S2 cleavage site found in SARS-CoV-2, but not in other βCoVs in lineage B, which is cleaved by furin pre-activating the viral S proteins during virus exit, reduces dependence of the viral S proteins on target cell proteases for virus entry and thus facilitates the virus infection [245].