LitCovid-sentences  

PubMed:32338224 JSONTXT 23 Projects

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Id Subject Object Predicate Lexical cue
T1 0-138 Sentence denotes Focus on Receptors for Coronaviruses with Special Reference to Angiotensin-converting Enzyme 2 as a Potential Drug Target - A Perspective.
T2 139-344 Sentence denotes Coronaviruses (CoVs) possess an enveloped, single, positive-stranded RNA genome which encodes for four membrane proteins, namely spike (S), envelope (E), membrane (M) and nucleocapsid (N) proteins 3-5 [1].
T3 345-439 Sentence denotes With regard to pathogenicity, S proteins are essential for viral entry into host cells [2, 3].
T4 440-721 Sentence denotes SARS-CoV binds to the angiotensin-converting enzyme (ACE)2 which is present on nonimmune cells, such as respiratory and intestinal epithelial cells, endothelial cells, kidney cells (renal tubules) and cerebral neurons and immune cells, such as alveolar monocytes/macrophages [4-6].
T5 722-925 Sentence denotes Of note, CD209L or liver/lymph node special intercellular adhesion molecule-3-grabbing non-integrin (SIGN) and dendritic cell (DC)-SIGN are alternative receptors for SARS-CoV but with lower affinity [7].
T6 926-1156 Sentence denotes In the case of MERS-CoV, S proteins bind to the host cell receptor dipeptidyl peptidase 4 (DPP4 or CD26) which is broadly expressed on intestinal, alveolar, renal, hepatic and prostate cells as well as on activated leukocytes [8].
T7 1157-1273 Sentence denotes Then, viruses replicate in target cells with release of mature virions, which, in turn, invade new target cells [9].
T8 1274-1490 Sentence denotes Evidence has been provided that SARSCoV proteins are cleaved into two subunits, S1 and S2, respectively, and the amino acids 318-510 of the S1 represent the receptor-binding domain (RBD) which binds to ACE2 [10, 11].
T9 1491-1647 Sentence denotes Quite importantly, in the context of RBD there is the receptor-binding motif (RBM) (amino acids 424- 494), which accounts for complete binding to ACE2 [11].
T10 1648-1758 Sentence denotes Moreover, by means of two residues at positions 479 and 487 RBD allows virus progression and tropism [10, 11].
T11 1759-1897 Sentence denotes In the case of MERSCoV, its RBM binds to DPP4 with residues 484-567, thus, suggesting that its RBD differs from that of SARS-CoV [12, 13].
T12 1898-2084 Sentence denotes In a very recent paper, Wan and associates [14] have investigated the receptor recognition by COVID-19 (a new term to indicate the 2019-nCoV in Wuhan) on the bases of structural studies.
T13 2085-2239 Sentence denotes In this respect, the sequence of COVID-19 RBM is similar to that of SARSCoV, thus, implicating that ACE2 may represent the binding receptors for COVID-19.
T14 2240-2393 Sentence denotes Furthermore, gln493 residue of COVID-19 RBM seems to allow interaction with human ACE2, thus, suggesting the ability of this virus to infect human cells.
T15 2394-2586 Sentence denotes According, to Wan and associates structural analysis [14], COVID-19 binds to human ACE2 with a lesser efficiency than human SARS-CoV (2002) but with higher affinity than human SARS-CoV (2003).
T16 2587-2791 Sentence denotes Furthermore, same authors predicted that a single mutation at the 501 position may enhance the COVID-19 RBD binding capacity to human ACE2 and this evolution should be monitored in infected patients [14].
T17 2792-2941 Sentence denotes These predictive findings by Wan and associates [14] are confirmed by two contemporary studies by Letko and Muster [15] and Peng and associates [16].
T18 2942-3055 Sentence denotes In particular, the report by Peng and associates [16], points out the possible origin of COVID-19 from bats [16].
T19 3056-3250 Sentence denotes From a pathogenic point of view, evidence has been provided that binding of S2 to ACE2 receptor leads to its down-regulation with subsequent lung damage in the course of SARS-CoV infection [17].
T20 3251-3446 Sentence denotes Down-regulation of ACE2 causes excessive production of angiotensin (ANG) II by the related enzyme ACE with stimulation of ANG type 1a receptor (AT1R) and enhanced lung vascular permeability [18].
T21 3447-3565 Sentence denotes In particular, same authors have reported that recombinant ACE2 could attenuate severe acute lung injury in mice [18].
T22 3566-3711 Sentence denotes Moreover, Battle and associates [19] also proposed to use already available recombinant ACE2 for intercepting COVID-19 and attenuating infection.
T23 3712-3898 Sentence denotes In the previous paragraphs, the presence of ACE2 on immune cells has been pointed out and, by analogy to epithelial cells, this receptor may also be down-regulated following viral entry.
T24 3899-4064 Sentence denotes Therefore, in CoV-infected animal models and in infected humans further investigations are required to clarify a possible reduced expression of ACE2 on immune cells.
T25 4065-4159 Sentence denotes In fact, in the course of SARS-CoV infection, a number of immune disorders have been detected.
T26 4160-4307 Sentence denotes Three reports have demonstrated the ability of CoV to inhibit interferon (IFN)- production in the course of SARS acting as IFN antagonist [20-22].
T27 4308-4512 Sentence denotes In senescent Balb/c mice, depletion of T lymphocytes is associated to more severe interstitial pneumonitis and delayed clearance of SARS-CoV, thus, suggesting a protective role played by these cells [23].
T28 4513-4662 Sentence denotes In this connection, both SARS-CoV and MERS-CoV have been shown to induce T cell apoptosis, thus, aggravating the clinical course of disease [24, 25].
T29 4663-4797 Sentence denotes Quite interestingly, memory CD8+ T cells specific for SARS-CoV M and N proteins have been detected up to 11 years post-infection [26].
T30 4798-4944 Sentence denotes As far as humoral immune responsiveness is concerned, evidence has been provided that S1 subunit from MERS-CoV is highly immunogenic in mice [27].
T31 4945-5122 Sentence denotes Moreover, monoclonal antibodies have been shown to be highly neutralizing against MERS-CoV replication and endowed with post exposure effectiveness in susceptible mice [28, 29].
T32 5123-5307 Sentence denotes Human neutralizing antibodies have also been isolated from a recovered patient, thus, suggesting the role of humoral immunity in the control of the persistence of CoV in the host [30].
T33 5308-5521 Sentence denotes In particular, IgG response occurs early in infection and its prolonged production may serve for virus clearance during recovery also in view of the absence of viremia in convalescent sera from SARS patients [31].
T34 5522-5714 Sentence denotes According to current literature, severity of COVID-19 infection correlates with lymphopenia and patients who died from COVID-19 had lower lymphocyte counts when compared to survivors [32, 33].
T35 5715-5816 Sentence denotes These data suggest that lymphocyte-mediated anti-viral activity is poorly effective against COVID-19.
T36 5817-6075 Sentence denotes Despite lymphopenia, evidence for an exaggerate release of proinflammatory cytokines [interleukin (IL)-1 and IL-6] has been reported in the course acute respiratory syndrome in COVID19 infected patients, thus, aggravating the clinical course of disease [34].
T37 6076-6262 Sentence denotes As recently reported, during COVID-19 pandemic in both Italy and China higher frequency of fatalities have been observed in the frail elderly population with previous comorbidities [35].
T38 6263-6426 Sentence denotes It is well known that decline of immunity occurs in ageing and, therefore, COVID-19 may gain easier access to the respiratory tract in frail elderly patients [36].
T39 6427-6579 Sentence denotes There is evidence that ACE2 protects from severe acute lung failure and operates as a negative regulator of the renin-angiotensin system (RAS) [18, 37].
T40 6580-6782 Sentence denotes It is well known that ANG II via activation of the AT1R promotes detrimental effects on the host, such as, vasoconstriction, reactive oxygen species generation, inflammation and matrix remodelling [38].
T41 6783-6934 Sentence denotes ACE2 counterbalances the noxious effects exhibited by ANG II and AT1R via activation of AT2R which arrests cell growth, inflammation and fibrosis [39].
T42 6935-7063 Sentence denotes In this framework, Gurwitz [40] proposed to use AT1R blockers, such as losartan, as a potential treatment of COVID-19 infection.
T43 7064-7251 Sentence denotes In fact, losartan as well as olmesartan, used for treating hypertension in patients, were able to increase ACE2 expression after 28 days treatment of rats with myocardial infarction [41].
T44 7252-7470 Sentence denotes Then, Gurwitz suggests to evaluate severity of symptoms in COVID-19 infected patients under previous chronic treatment with AT1R blockers in comparison to COVID-19 infected patients who did not take AT1R blockers [40].
T45 7471-7597 Sentence denotes Quite interestingly, 75% of aged COVID-19 infected patients admitted to Italian hospitals had hypertension [unpublished data].
T46 7598-7745 Sentence denotes However, the putative effects of ACE-2 down-regulation on the cardiovascular system in the course of COVID-19 pandemic need more intensive studies.
T47 7746-7930 Sentence denotes Taken together, these evidences suggest that CoV-induced down-regulation of ACE2 activates RAS with collateral damage to organs, such as lungs, in the course of SARS-related pneumonia.
T48 7931-8074 Sentence denotes Then, putative therapeutic measures aimed at increasing ACE2 levels on respiratory epithelial cells should be taken into serious consideration.
T49 8075-8348 Sentence denotes Quite interestingly, over the past few years, three key papers have demonstrated the ability of a polyphenol, resveratrol (RES), to experimentally deactivate the RAS system in maternal and post-weaning high fat diet, arterial ageing and high fat diet, respectively [42-44].
T50 8349-8546 Sentence denotes In all these experimental models, RES led to an increase of ACE2 with reduction of organ damage, such as liver steatosis and aorta media thickness and decrease of adipose tissue mass, respectively.
T51 8547-8662 Sentence denotes As far as the mechanism of action of RES is concerned, this polyphenol is able to activate sirtuin (Sirt)1 [45-47].
T52 8663-8741 Sentence denotes In turn, Sirt1 down-regulates AT1R expression via ACE2 up-regulation [43, 48].
T53 8742-8947 Sentence denotes Of importance, Lin and associates [48] have demonstrated the ability of RES to in vitro inhibit MERS-CoV infection of Vero E6 cells, thus, prolonging cell survival in virtue of an anti-apoptotic mechanism.
T54 8948-9012 Sentence denotes These findings suggest a direct antiviral effect exerted by RES.
T55 9013-9104 Sentence denotes It would be very interestingly to evaluate the direct effects of RES on COVID-19, in vitro.
T56 9105-9374 Sentence denotes The data above discussed strongly suggest, that RES, as an activators of ACE2, should be investigated in animal models of CoV-induced severe pneumonia, also taking into account the antioxidant, anti-inflammatory and immunomodulating effects exerted by polyphenols [49].
T57 9375-9478 Sentence denotes Then, successful animal studies may pave the way for RES-based human trials in COVID-infected patients.
T58 9479-9589 Sentence denotes Note added in proof During the reviewing process of this perspective other related papers have been published.
T59 9590-9765 Sentence denotes Hanff and associates [50] have discussed the possible association between COVID-19-associated cardiovascular mortality and dysregulation of the Renin Angiotensin System (RAS).
T60 9766-9939 Sentence denotes From a pharmacologic point of view, RAS inhibition leads to upregulation of ACE2, thus, attenuating acute respiratory syndrome and myocarditis in COVID-19-infected patients.
T61 9940-10072 Sentence denotes Conversely, increase in ACE2 expression may facilitate the access into the host of COVID-19, thus, aggravating the clinical picture.
T62 10073-10190 Sentence denotes Such a dilemma would be solved by clinical trials based on RAS blockade or initiation and monitoring related effects.
T63 10191-10323 Sentence denotes Contemporarily, Danser and associates [51] claim that there is no evidence to stop RAS blockers in the course of COVID-19 infection.
T64 10324-10482 Sentence denotes In fact, there are no available data which support that ACE inhibitors or ANG II type I receptor blockers increase COVID-19 infection via its binding to ACE2.
T65 10483-10621 Sentence denotes Finally, Kuster and associates [52] write that there are no data on the strict relationship between ACE2 activity and SARS-CoV2 mortality.
T66 10622-10767 Sentence denotes Moreover, in the SARSCoV2, cells expressing ACE2 were not attacked by the virus, while cells lacking ACE2 were bound by the SARS-CoV2 virus [53].
T67 10768-10916 Sentence denotes These findings suggest that also in the case of RES effects on COVID-19 infection, the dual role of ACE2 should be taken into serious consideration.