LitCovid-sentences  

PMC:7205724 / 1763-30161 JSONTXT 28 Projects

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Id Subject Object Predicate Lexical cue
T21 0-15 Sentence denotes 1 Introduction
T22 16-139 Sentence denotes Several generations have been exposed to COVID-19 under different conditions of life at varying locations around the world.
T23 140-246 Sentence denotes As long as the COVID-19 continues to spread, its power of genome modification would probably be increased.
T24 247-501 Sentence denotes What concerns us more is that the 2019-nCoV, by the process of modification of genome structure, might become more and more fitted to humans to profoundly affect those who have already escaped – children and young people without a pre-existing condition.
T25 502-656 Sentence denotes No one can tell how much time it takes to reach a new level of perfection, and that the development of vaccines for active immunization is a long process.
T26 657-757 Sentence denotes Moreover, most of the best available anti-viral agents are not helpful in the treatment of COVID-19.
T27 758-1049 Sentence denotes A randomized controlled trial of 199 hospitalized adults with confirmed COVID-19 demonstrated no actual difference between patients who received lopinavir-ritonavir and patients who received standard care alone in clinical improvement, death rate, and positive virus test rate at day 28 [1].
T28 1050-1195 Sentence denotes Here we review intermediate indicators of the pathogenesis of COVID-19 that have the potential of being considered for the treatment of COVID-19.
T29 1197-1235 Sentence denotes 2 SARS-CoV2 cell entry is not complex
T30 1236-1340 Sentence denotes Fig. 1 is a schematic illustration of the minimum proteins required to mediate the SARS-CoV2 cell entry.
T31 1341-1465 Sentence denotes The trimeric, transmembrane spike (S) glycoprotein of the virus, SARS-2-S, includes two main functional subunits: S1 and S2.
T32 1466-1620 Sentence denotes The former, in turn, consists of the four core domains, S1A, S1B, S1C, and S1D, that contribute to the attachment to the surface receptor of target cells.
T33 1621-1693 Sentence denotes Then, the latter coordinates the fusion of viral and cellular membranes.
T34 1694-1788 Sentence denotes Receptor binding activates proteases that can carry out proteolytic cleavage of the S protein.
T35 1789-1919 Sentence denotes In coronaviruses, cleavage occurs at two sites: the S1/S2 junction and at the S2′, a region close to the viral fusion peptide [2].
T36 1920-2132 Sentence denotes Proteolytic cleavage of the S protein causes conformational changes so that they cannot revert to the original structure and profound enough to prime the S2 subunit for the fusion of viral and cellular membranes.
T37 2133-2187 Sentence denotes Fig. 1 Proteins required for the SARS-CoV2-cell entry.
T38 2189-2228 Sentence denotes 3 Certain characteristics of SARS-CoV2
T39 2230-2333 Sentence denotes 3.1 SARS-CoV2 has acquired an S glycoprotein that highly underwent genetic variation and glycosylation
T40 2335-2365 Sentence denotes 3.1.1 Polybasic cleavage site
T41 2366-2537 Sentence denotes As evidenced by sequence analysis, there is a residue insertion formed of four amino acids (12 nucleotides) at the boundary between S1 and S2 subunits of the SARS-CoV 2 S.
T42 2538-2740 Sentence denotes It defines a polybasic furin cleavage site of RRAR for the human SARS-CoV 2 that was absent in human SARS-CoV, bat SARS-like CoVs, and pangolin SARS-like CoV while might be present in other species [3].
T43 2741-2891 Sentence denotes After the introduction of mutation to the residue insertion and furin cleavage site, the S1/S2 cleavage of the SARS-CoV 2 S did not longer take place.
T44 2892-3002 Sentence denotes However, the SARS-CoV 2 S entry raised for VeroE6 cells and remained high in BHK cells that express human ACE.
T45 3003-3093 Sentence denotes Therefore, it seems that SARS-CoV2 transmissibility does not depend on the S1/S2 cleavage.
T46 3094-3219 Sentence denotes A polybasic cleavage site explains a virus that is highly-pathogenic for humans while it is low-pathogenic for other species.
T47 3220-3368 Sentence denotes For example, using reverse genetic tools, an avian paramyxovirus type 7 (APMV-7) was developed by mutating the fusion (F) protein cleavage site [4].
T48 3369-3481 Sentence denotes The constructed APMV-7 showed furin cleavage and increased replication and syncytium formation in cell cultures.
T49 3482-3546 Sentence denotes However, chicken exposed to the virus did not exhibit infection.
T50 3548-3568 Sentence denotes 3.1.2 Glycosylation
T51 3569-3739 Sentence denotes Glycosylation and its related products, i.e., glycans, introduce changes to the viral envelope that make the virus fitted for interaction with the host cell membrane [5].
T52 3740-3837 Sentence denotes Generally, glycans are oligosaccharides linked to the dense decoration of the spike glycoprotein.
T53 3838-3998 Sentence denotes In particular, these oligosaccharides have shown to influence the folding of the S protein and proteolytic process so that they facilitate the virus cell entry.
T54 3999-4115 Sentence denotes Moreover, a virus with the glycosylated glycoprotein gains an extra feature for an escape from the immune responses.
T55 4116-4172 Sentence denotes Therefore, glycans are a good target for vaccine design.
T56 4173-4233 Sentence denotes Two main types of glycans are N-linked and O-linked glycans.
T57 4234-4271 Sentence denotes Both are released from glycoproteins.
T58 4272-4377 Sentence denotes Whereas enzymes fulfill the construction of N-glycans, chemical methods perform the release of O-glycans.
T59 4378-4555 Sentence denotes N-glycans are linked to the amino acid asparagine (Asn) residues (Asn-any amino acids except for proline- Ser or Thr) utilizing an N-glycosidic bond, mostly N-acetylglucosamine.
T60 4556-4693 Sentence denotes O-glycans are attached to the amino acid serine (Ser) and threonine (Thr) residues by the addition of an N-acetyl galactosamine (GalNAc).
T61 4694-4863 Sentence denotes For example, N-glycans exist in Hendra virus, SARS-CoV, influenza virus, hepatitis virus, HIV-1, and West Nile virus [6], and O-glycans have occurred in the Ebola virus.
T62 4864-4979 Sentence denotes The 2019-nCoV S protein includes 13 and 9N-linked glycosylation sequons in the S1 and S2 subunit, respectively [3].
T63 4980-5105 Sentence denotes All of these have previously occurred in the SARS-CoV S glycoprotein, except for four-linked glycosylation sequons in the S1.
T64 5106-5329 Sentence denotes Also, due to the existence of an amino acid proline in the polybasic cleavage site, which makes the inserted sequence PRRA, there are three O-linked glycans introduced to the 2019-nCoV RBD residues S673, T678, and S686 [7].
T65 5331-5452 Sentence denotes 3.1.3 SARS-CoV2 receptor binding domain contains six amino acids providing favorable positions for binding to human ACE2
T66 5453-5678 Sentence denotes When compared to SARS-CoV SB, the motif binding the human ACE2 to the SARS-CoV 2 SB showed a relatively higher binding affinity for human ACE2 as indicated in smaller equilibrium dissociation constant (2.9 nM vs. 7.7 nM) [3].
T67 5679-6063 Sentence denotes Structural analysis has demonstrated that fourteen positions critically take part in the receptor-binding domain of the SARS-CoV SB that contain eight conserved (T402, Y436, Y440, N473, Y475, T486, G488, and Y491) positions and six semi-conserved (R426 to N448, Y442 to L464, L472 to F495, N479 to Q502, Y484 to Q507, and T487 to N510) substitutions with respect to the SARS-CoV 2 SB.
T68 6065-6179 Sentence denotes 3.1.4 SARS-CoV2 receptor binding domain contains cyclic regions that can make interaction with cell-surface GRP78
T69 6180-6369 Sentence denotes Pep42 is a cyclic oligopeptide that, with its hydrophobic character, can selectively interact with cell surface glucose‐regulated protein 78 (GRP78), a member of 70 kDa heat shock proteins.
T70 6370-6591 Sentence denotes GRP78, also known as BiP or HSPA5, under endoplasmic reticulum stress, can be translocated from the endoplasmic reticulum to the membrane and helps to maintain cellular integrity under physiologic and pathological stress.
T71 6592-6783 Sentence denotes It critically contributes to various functions ranging from protein folding, transportation, and degradation to cell-signaling, proliferation, survival, apoptosis, inflammation, and immunity.
T72 6784-6827 Sentence denotes The expression of GRP78 decreases with age.
T73 6828-6982 Sentence denotes On the 2019-nCoV spike protein, 13 disulfide bonds are corresponding to 13 different cyclic regions thought to be similar to the cyclic form of Pep42 [8].
T74 6983-7148 Sentence denotes Among these, four regions I-IV take place in the outer surface of a putative receptor-binding domain (RBD) on the viral spike., including C361, C379, C391, and C480.
T75 7149-7231 Sentence denotes These regions share sequence similarity with Pep42, ranging from 15.38% to 46.15%.
T76 7232-7341 Sentence denotes However, only one of them, i.e., region IV (GRAVY = 0.08), is a hydrophobic region, like Pep42 (GRAVY = 1.1).
T77 7342-7566 Sentence denotes Structural models evaluate the energy contribution for region IV as a part of region III to the GRP78 to be about (−9.8 out of −14.0 kcal/mol), and the docking platform proposes region IV as the best region binding to GRP78.
T78 7567-7766 Sentence denotes The region IV can be linked to the substrate-binding domain β (SBDB) of GRP78 using five H-bonds (through P479, N481, E484, and N487) and four hydrophobic interactions (through T478, E484, and F486).
T79 7768-7791 Sentence denotes 4 Passive immunization
T80 7792-7889 Sentence denotes There are two main ways to induce protection against infections: active and passive immunization.
T81 7890-8029 Sentence denotes Active immunization comes to exist when the body's own immune system can produce antibodies actively following exposure to a viral antigen.
T82 8030-8205 Sentence denotes On the contrary, there is a passive working mode of the immune system that would appear following the transfer of antibodies that act directly to neutralize viral infectivity.
T83 8207-8225 Sentence denotes 4.1 Serum therapy
T84 8227-8291 Sentence denotes 4.1.1 Convalescent plasma from patients recovered from COVID-19
T85 8293-8313 Sentence denotes 4.1.1.1 Hypothesis:
T86 8314-8395 Sentence denotes Plasma from patients recovered from COVID-19 contain antibodies against 2019-nCoV
T87 8396-8511 Sentence denotes A look at the history of viral outbreaks offers convalescent plasma as the only remedy to avoid further fatalities.
T88 8512-8706 Sentence denotes The most recent examples include the pandemic of influenza A H1N1 (H1N1pdm09) in virus infection 2009, the Western African Ebola virus epidemic in 2014, and the outbreak of MERS-CoV in 2015 [9].
T89 8707-8843 Sentence denotes Meta-analysis studies have shown a reduced risk of mortality in patients with SARS-CoV and influenza receiving convalescent plasma [10].
T90 8845-8864 Sentence denotes 4.1.1.2 Rationale:
T91 8865-8962 Sentence denotes Convalescent plasma from patients recovered from COVID-19 can treat patients with severe COVID-19
T92 8963-9227 Sentence denotes A pilot study [11] recently has investigated the safety and effect of convalescent plasma that contain antibody levels higher than 1:640 combined with regular anti-viral agents and standard supportive care on clinical outcomes of ten patients with severe COVID-19.
T93 9228-9359 Sentence denotes The study showed clinical improvement of all the ten patients accompanied by an increase in lymphocyte count and a decrease in CRP.
T94 9360-9529 Sentence denotes Following transfusion of convalescent plasma, all the seven patients who were SARS-CoV2 RNA positive before transfusion of convalescent plasma turned SARS-CoV2 negative.
T95 9530-9695 Sentence denotes There were no control groups receiving convalescent plasma alone or standard therapy without convalescent therapy to evaluate the main effect of convalescent plasma.
T96 9697-9738 Sentence denotes 4.1.2 Serum from bats with SARS-like CoV
T97 9740-9909 Sentence denotes 4.1.2.1 Hypothesis: whole-genome sequencing and phylogenetic analysis shed light on the origin of the 2019-nCoV virus – It has been probably introduced from bats to men
T98 9910-10086 Sentence denotes Genome sequencing of a fecal bat sample, Rp3, could detect an isolate of coronaviruses, which was almost identical to the causative agent of the SARS-CoV outbreak of 2002–2003.
T99 10087-10167 Sentence denotes Hence, it attained the name SARS-like coronavirus isolate Rp3 (SL-CoV Rp3) [12].
T100 10168-10255 Sentence denotes The bronchoalveolar lavage fluid (BALF) of a patient with SARS contained the 2019-nCoV.
T101 10256-10421 Sentence denotes RNA sequencing could reveal about 90% similarity in nucleotides of the novel coronavirus and of SARS-like coronavirus that had previously related to bats [13], [14].
T102 10422-10599 Sentence denotes In particular, the S protein of the 2019-nCoV has a high sequence identity of 80–98% with the S protein of bat SARS-like CoVs, such as SARSr-CoV ZXC21 S, ZC45 S, and RaTG13 [3].
T103 10600-10753 Sentence denotes Moreover, in phylogenomic trees, branches for the 2019-nCoV are of greater length than those for the 2003 SARS-CoV, and therefore more favorable to bats.
T104 10755-10774 Sentence denotes 4.1.2.2 Rationale:
T105 10775-10831 Sentence denotes Bat serum is not able to efficiently neutralize SARS-CoV
T106 10832-10968 Sentence denotes The range of bats, belonging to the genus Rhinolophus (horseshoe bats) and the family Rhinolophidae, produce the SARS-CoV antibody [12].
T107 10969-11159 Sentence denotes Polymerase chain reaction (PCR) will confirm the presence of SARS-CoV nucleocapsid (N) and polymerase (P) proteins in fecal samples if an individual bat being seropositive for SARS-CoV [12].
T108 11160-11366 Sentence denotes There is a significant degree of resemblance of greater than 90% in the nucleotide sequence of the viral genomes between SL-CoV Rp3 [12] and the Tor2 strain of SARS-CoV – which was isolated in Toronto [15].
T109 11367-11579 Sentence denotes The differences in the genome sequences of SARS-CoV in the two species occur merely in the S gene – which encodes the S1 domain of the coronavirus spike protein and contains regions with high mutation rates [12].
T110 11580-11808 Sentence denotes The coronaviruses commonly possess five open reading frames (ORF) that correlate with the production of the replicase polyprotein (P), the spike (S), envelope (E), and membrane (M) glycoproteins and the nucleocapsid (N) protein.
T111 11809-11966 Sentence denotes The human SARS-CoV Tor2 and bat SL-CoV Rp3 strains remain more than 90% identical at the proteins P, E, M, and N. the protein S consists of two main domains:
T112 11967-12106 Sentence denotes 1) the S1 domain conveys the role of receptor binding and 2) the S2 domain assumes the role of the fusion of viral and host-cell membranes.
T113 12107-12241 Sentence denotes In particular, the human SARS-CoV Tor2 strain shows a noticeable degree of difference in the S1 domain from the bat SL-CoV Rp3 strain.
T114 12242-12458 Sentence denotes This diversity would suffice to produce functional differences between the species, and is an apparent reason why bat sera having high levels of cross-reactive antibodies not acted efficiently to neutralize SARS-CoV.
T115 12460-12504 Sentence denotes 4.1.3 Serum from convalescent SARS patients
T116 12506-12627 Sentence denotes 4.1.3.1 Hypothesis: SARS-CoV and SARS-CoV2 are ideally similar in the structure and the cell entry receptor and protease
T117 12628-12990 Sentence denotes SARS-CoV and SARS-CoV2 share absolutely the same cleavage junctions, almost the same sequence (96%) of their main protease, a high degree (76%) of similarity in the amino acid sequence of their S protein, a similar S2′ cleavage site, a similar spectrum of cells they can enter, and the similarity of the most residues essential for binding ACE2 [16], [17], [18].
T118 12991-13076 Sentence denotes Also, both of them utilize the same domain of S1B to interact with the ACE2 receptor.
T119 13077-13139 Sentence denotes However, they differ in proteolytic processing to some degree.
T120 13140-13334 Sentence denotes Study [16] of the human embryonic kidney (HEK) cell line, 293 T, has shown that a signal for the S2 subunit is present in cells inoculated with SARS-2-S, but not in cells inoculated with SARS-S.
T121 13335-13496 Sentence denotes Two main proteases for both SARS-S and SARS-2-S are endosomal cysteine proteases cathepsin B and L (CatB/L) and the transmembrane protease, serine 2TMPRSS2 [16].
T122 13497-13676 Sentence denotes In 293 T cells lacking 2TMPRSS2, blocking CatB/L activity through increasing the endosomal pH by ammonium chloride could significantly limit the entry of both SARS-S and SARS-2-S.
T123 13677-13763 Sentence denotes In TMPRSS2 + Caco-2 cells, the effect of ammonium chloride existed to a lesser extent.
T124 13764-13933 Sentence denotes A combination of camostat mesylate, a blocker of TMPRSS2, and E-64d, an inhibitor of CatB/L, yielded the complete inhibition of SARS-2-S entry in TMPRSS2 + Caco-2 cells.
T125 13934-14183 Sentence denotes In both the human lung cancer cell line Calu-3 and the primary human lung cells, there was a reduction of the entry of both SARS-S and SARS-2-S by camostat mesylate, indicating that SARS-S and SARS-2-S partially require TMPRSS2 for a lung infection.
T126 14185-14203 Sentence denotes 4.1.3.2 Rational:
T127 14204-14285 Sentence denotes Serum from convalescent SARS patients is able to neutralize SARS-CoV2 efficiently
T128 14286-14464 Sentence denotes Antiserum that contains antibodies against human ACE2 could hinder the entry of both SARS-S and SARS-2-S pseudotypes while not affected the entry of VSV-G and MERS-S pseudotypes.
T129 14465-14687 Sentence denotes It supports the notion that SARS-S and SARS-2-S utilize the same primary entry receptor, i.e., ACE2, which is different from the primary receptors VSV-G and MERS-S engage for cell entry that is LDLR and DPP4, respectively.
T130 14688-14800 Sentence denotes Sera from three convalescent SARS patients reduced the SARS-S entry and, to e lesser degree, the SARS-2-S entry.
T131 14801-14862 Sentence denotes The patient serum effect was in a dose-dependent manner [16].
T132 14864-14909 Sentence denotes 4.1.4 Serum from rabbits immunized with SARS
T133 14911-14931 Sentence denotes 4.1.4.1 Hypotheses:
T134 14932-15031 Sentence denotes Serum from rabbits immunized with SARS is more effective than serum from convalescent SARS patients
T135 15032-15137 Sentence denotes Paraoxonases (PON) are mammalian enzymes associated with anti-oxidant and anti-inflammatory effects [19].
T136 15138-15246 Sentence denotes Rabbit PON differs from human PON in terms of more activity and more stability under the circumstances [20].
T137 15248-15266 Sentence denotes 4.1.4.2 Rational:
T138 15267-15374 Sentence denotes Serum from rabbits immunized with the S1 subunit of SARS-S is able to neutralize SARS-CoV2 very efficiently
T139 15375-15501 Sentence denotes Sera from rabbits immunized with the S1 subunit of SARS-S could effectively reduce the entry of both SARS-S and SARS-2-S [16].
T140 15502-15640 Sentence denotes When compared with patient serum, rabbit serum revealed to us higher efficiency in inhibition of SARS-2-S entry at the same concentration.
T141 15642-15681 Sentence denotes 4.2 Intravenous immunoglobulins (IVIG)
T142 15683-15748 Sentence denotes 4.2.1 Hypothesis: IVIG contains a large pool of human antibodies
T143 15749-15936 Sentence denotes IVIG is an immunomodulatory treatment currently useful for a variety of human diseases that share an idiopathic origin, ranging from autoimmune disorders to primary antibody deficiencies.
T144 15937-16245 Sentence denotes Also, IVIG has shown promising results in case of severe (such as sepsis, Parvovirus B19 infection, West Nile virus encephalitis, HIV, Clostridium difficile infections, Mycobacterium avium, Mycobacterium tuberculosis, and Nocardia infections) and recurrent infections in primary antibodies deficiencies [21].
T145 16246-16365 Sentence denotes Most patients develop antibodies against the NP and RBD of 2019-nCoV during the second week after infection onset [22].
T146 16366-16561 Sentence denotes Analysis of serum samples collected 14 or more days after symptom onset revealed detection of IgG and IgM antibodies against NP in 94% and 88% and RBD in 100% and 94% among patients with COVID19.
T147 16562-16687 Sentence denotes Studies consistently show that increased immunoglobulin levels accompany the transition from early to late course of COVID19.
T148 16688-16779 Sentence denotes It poses the possibility that IVIG therapy might help to accelerate recovery from COVID-19.
T149 16781-16863 Sentence denotes 4.2.2 Rationale: IVIG might help to improve the outcome of patients with COVID-19
T150 16864-17163 Sentence denotes The study [23] included ten patients with COVID-19 who demonstrated worsening symptoms, e.g., decreased lymphocyte count and decreased PaO2/FIO2 ratio and oxygen saturation, following treatment with a short-term moderate-dose corticosteroid (methylprednisolone 80 mg/d) plus immunoglobulin (10 g/d).
T151 17164-17343 Sentence denotes After switching to the double dose of 1600 mg/d methylprednisolone plus 20 g/d immunoglobulin, all of the patients improved in the clinical, laboratory, and paraclinical outcomes.
T152 17344-17475 Sentence denotes Passive immunization protects against disease, and so it should be administered as early as possible when the patient is diagnosed.
T153 17476-17707 Sentence denotes Studies show that the viral RNA of 2019-nCoV reaches its peak during the first week and then gradually decreases and that IgG and IgM begin to rise from the 10th day so that most patients have anti-viral antibodies by the 14th day.
T154 17709-17734 Sentence denotes 5 Recombinant type I IFN
T155 17736-17792 Sentence denotes 5.1 Hypothesis: IFNs play a role in anti-viral immunity
T156 17793-17966 Sentence denotes Type I IFNs play a primary role in the inhibition of viral replication through the coordination of anti-viral immune responses and modulation of inflammatory responses [24].
T157 17968-17982 Sentence denotes 5.2 Rational:
T158 17983-18051 Sentence denotes Recombinant type I IFN can effectively inhibit SARS-CoV2 replication
T159 18052-18240 Sentence denotes In 24–48 h after infection, SARS-CoV2 replication reaches titer that causes the cytopathic effect in Vero E6 cells, which express ACE2 and thus are susceptible to SARS-CoV2 infection [25].
T160 18241-18307 Sentence denotes It is similar to the viral replication kinetics for SARS-CoV [25].
T161 18308-18438 Sentence denotes Pretreatment with recombinant type I IFN could effectively inhibit SARS-CoV2 replication at both 24 and 48 h after infection [25].
T162 18439-18528 Sentence denotes For SARS-CoV, such an effect was present at 24 h but absent at 48 h after infection [25].
T163 18529-18715 Sentence denotes The difference between SARS-CoV2 and SARS-CoV in response to type I IFN treatment may be due to differences in structural proteins of these viruses, including NSP3, ORF3b, and ORF6 [25].
T164 18717-18768 Sentence denotes 6 Development of a human monoclonal antibody (mAb)
T165 18770-18798 Sentence denotes 6.1 Targeting the S protein
T166 18800-18818 Sentence denotes 6.1.1 Hypothesis:
T167 18819-18896 Sentence denotes A mAb against the binding domain of the virus can inhibit SARS-CoV2 infection
T168 18897-19183 Sentence denotes Recently, hybridoma supernatants containing antibody repertoires from immunized transgenic mice that express the human immunoglobulin heavy and light chains and rat origin immunoglobulin constant regions were used to detect antibodies that can cross neutralize SARS-S and SARS-2-S [26].
T169 19184-19404 Sentence denotes One chimeric 47D11 H2L2 antibody displayed such a cross-neutralizing activity, decreased syncytia formation induced by SARS-S and SARS2-S, and could protect VeroE6 cells against SARS-S and SARS2-S pseudotyped virus [26].
T170 19405-19537 Sentence denotes It may lie in its similar affinities for interacting with the same domain of the S1 subunit, i.e., S1B, of each SARS-S and SARS-2-S.
T171 19539-19555 Sentence denotes 6.1.2 Rational:
T172 19556-19640 Sentence denotes The chimeric 47D11 H2L2 might not be effective in human lung cells as it is in vitro
T173 19641-19741 Sentence denotes 47D11 carried a higher affinity for interacting with the S2 subunit of SARS-S than that of SARS-2-S.
T174 19742-19923 Sentence denotes It is important that for both SARS-S and SARS-2-S, the binding of the 47D11 antibody to the target – the S1B domain – does not block the binding of S1B and S2 to ACE2 receptor [26].
T175 19924-20043 Sentence denotes By contrast, neutralizing antibodies that specifically target SARS-S could compete with S1B and S2 for binding to ACE2.
T176 20045-20086 Sentence denotes 6.2 Targeting pro-inflammatory cytokines
T177 20088-20106 Sentence denotes 6.2.1 Hypothesis:
T178 20107-20157 Sentence denotes A mAb against IL6 can attenuate hyper inflammation
T179 20158-20486 Sentence denotes Tocilizumab, also known as atlizumab, is a humanized anti-human IL6 receptor antibody approved by FDA for several inflammatory and autoimmune diseases severe, such as cytokine release syndrome, rheumatoid arthritis, giant cell arteritis, polyarticular juvenile idiopathic arthritis, and systematic juvenile idiopathic arthritis.
T180 20487-20568 Sentence denotes It is safe and effective for both adults and children two years of age and older.
T181 20570-20587 Sentence denotes 6.2.2 Rationale:
T182 20588-20667 Sentence denotes Tocilizumab can treat lung injury in patients with critical and severe COVID-19
T183 20668-20815 Sentence denotes In the study [27], 21 patients with COVID-19 whose condition was severe or critical received one or two doses of Tocilizumab plus standard therapy.
T184 20816-21034 Sentence denotes Patients who had a mean IL6 level of more than 100 pg/ml before tocilizumab treatment showed improvement in clinical symptoms and peripheral oxygen saturation and normalization for lymphocyte proportion and CRP levels.
T185 21035-21093 Sentence denotes Also, lung lesion opacity was absorbed in 90% of patients.
T186 21094-21173 Sentence denotes Neither serious adverse effects nor deaths occurred with tocilizumab treatment.
T187 21174-21280 Sentence denotes There are ongoing clinical trials for tocilizumab treatment in patients with moderate and severe COVID-19.
T188 21281-21496 Sentence denotes Currently, the use of Tocilizumab is recommended for patients with COVID-19 who have warning signs of hyper inflammation, as can be measured by IL6, ferritin, platelet counts, inflammatory markers, and H score [28].
T189 21498-21516 Sentence denotes 7 Corticosteroids
T190 21518-21534 Sentence denotes 7.1 Hypothesis:
T191 21535-21576 Sentence denotes Corticosteroids can modulate inflammation
T192 21577-21666 Sentence denotes Corticosteroids are commonly used for modulation of a variety of inflammatory conditions.
T193 21667-21784 Sentence denotes In addition to a daily regimen, they can be used in the form of pulse therapy to treat flares of autoimmune diseases.
T194 21785-21983 Sentence denotes However, caution in the use of corticosteroids is needed due to the potential serious side effects associated with corticosteroid drugs and that corticosteroids generally suppress the immune system.
T195 21984-22158 Sentence denotes The latter means that corticosteroids modulate hyper inflammation and, on the other hand, inhibit immune responses that are vital for the host defense against the virus [29].
T196 22160-22175 Sentence denotes 7.2 Rationale:
T197 22176-22236 Sentence denotes Corticosteroids might help accelerate recovery from COVID-19
T198 22237-22407 Sentence denotes The study [30] investigated the effect of inhaled corticosteroids ciclesonide, cortisone, prednisolone, dexamethasone, and fluticasone on the replication of the MERS-CoV.
T199 22408-22499 Sentence denotes Among the four compounds, the only ciclesonide was capable of inhibiting viral replication.
T200 22500-22807 Sentence denotes Also, ciclesonide induced a significant inhibition of viral replication of other human coronaviruses, such as HCoV-229E and SARS-CoV, and another positive-strand RNA virus, rubella virus, while not affect the viral replication of negative-strand RNA viruses, e.g., influenza and respiratory syncytial virus.
T201 22808-22906 Sentence denotes For the MERS-CoV, a nonstructural protein 15 (NSP15) appeared to act as the target of ciclesonide.
T202 22907-23007 Sentence denotes An amino acid substitution in the NSP15 conferred resistance of the mutated MERS-CoV to ciclesonide.
T203 23008-23073 Sentence denotes Mometasone could help deal effectively with the mutated MERS-CoV.
T204 23074-23201 Sentence denotes For the SARS-CoV2, all three ciclesonide, mometasone, and lopinavir were able to inhibit viral replication to a similar degree.
T205 23202-23359 Sentence denotes Interestingly, their effect was more noticeable than serine protease inhibitors, e.g., nafamostat and camostat in cells that Vero cells that express TMPRSS2.
T206 23360-23514 Sentence denotes It indicates the tendency of the SARS-CoV2 to enter the cell through the cathepsin/endosomal pathway rather than through the TMPRSS2/cell surface pathway.
T207 23515-23719 Sentence denotes The study [31] included 46 patients with severe COVID-19, of these 26 patients received methylprednisolone (1–2 mg/kg/d for 5–7 days), and 20 patients received standard therapy without methylprednisolone.
T208 23720-23866 Sentence denotes The first group achieved faster improvement in clinical symptoms (fever and peripheral oxygen saturation) and lung lesions detected by CT imaging.
T209 23867-23949 Sentence denotes However, two deaths occurred in the first group and one death in the second group.
T210 23950-24134 Sentence denotes Moreover, the two groups did not differ in laboratory parameters, including WBC, lymphocyte count, monocyte count, and cytokines (IL-2, IL-4, IL-6, and IL-10) six days after treatment.
T211 24135-24248 Sentence denotes There is a report of the patient with COVID-19 treated with methylprednisolone since day 8 of the disease course.
T212 24249-24339 Sentence denotes However, his situation worsened and developed respiratory failure and died on day 14 [32].
T213 24341-24379 Sentence denotes 8 Eggs for increasing ACE2 and copper
T214 24380-24549 Sentence denotes Egg ovotransferrin contains an angiotensin-converting enzyme (ACE) inhibitory peptide, known as IRW, that has shown to decrease blood pressure in hypertensive rats [33].
T215 24550-24732 Sentence denotes Through the up-regulation of ACE2, E-cadherin, ABCB-1, and IRF-8, IRW can decrease RAS activity, hyperplasia, and vascular inflammation and aid differential regulation of leukocytes.
T216 24733-24902 Sentence denotes On the other hand, by the down-regulation of pro-inflammatory molecules, e.g., ICAM-1 and VCAM-1, IRW can reduce the recruitment of leukocytes and vascular inflammation.
T217 24903-24966 Sentence denotes Copper might help the immune system to combat viral infections.
T218 24967-25039 Sentence denotes A High-content of copper exists in eggs and eggshells of domestic birds.
T219 25040-25178 Sentence denotes In particular, the eggshell of pigeon (4 ± 0.29 μg/g) and the egg of quail (4.67 ± 1.08 μg/g) contains high concentrations of copper [34].
T220 25180-25193 Sentence denotes 9 Conclusion
T221 25194-25287 Sentence denotes The novel coronavirus, SARS-CoV2, can cause a potentially fatal disease, COVID-19, in humans.
T222 25288-25468 Sentence denotes The infection of human cells by SARS-CoV2 includes two sequential steps: attachment of the virus to the surface receptor of target cells and the fusion of viral and host membranes.
T223 25469-25647 Sentence denotes The former requires at least a receptor-binding domain on the SARS-CoV2 Spike protein that can interact with a cell surface receptor, for example, ACE2, expressed on human cells.
T224 25648-25849 Sentence denotes The latter requires at least the host protease(s) to mediate proteolytic cleavage of the SARS-CoV2 Spike protein into S1 and S2 subunits and consequently promote the fusion of viral and host membranes.
T225 25850-26096 Sentence denotes Also, SARS-CoV2 possesses a polybasic cleavage site that can explain the high pathogenicity of SARS-CoV2, N-glycans and O-glycans that make the dense decoration of SARS-CoV2 S protein, and cyclic regions that can interact with cell-surface GRP78.
T226 26097-26279 Sentence denotes Essential elements that process SARS-CoV2 cell entry and specific characteristics that allow SARS-CoV2 to escape the immune system have the potential as targets for COVID-19 therapy.
T227 26280-26476 Sentence denotes Lack of specific treatments for COVID-19 and the very time-consuming process of vaccine development lead us to trust traditional notions of immunization using passive transfer of humoral immunity.
T228 26477-26548 Sentence denotes Passive immunization can be done using plasma therapy and IVIG therapy.
T229 26549-26698 Sentence denotes Plasma from patients recovered from COVID-19 that contains antibodies against SARS-CoV2 has shown promising results in patients with severe COVID-19.
T230 26699-26806 Sentence denotes Also, SARS-CoV and SARS-CoV2 are ideally similar in the structure and the cell entry receptor and protease.
T231 26807-26956 Sentence denotes Studies show that serum from convalescent SARS patients and serum from rabbits immunized with SARS are both able to neutralize SARS-CoV2 efficiently.
T232 26957-27061 Sentence denotes However, serum from bats immunized with SARS-lice coronavirus SL-CoV Rp3 could not exert such an effect.
T233 27062-27191 Sentence denotes It is due to a noticeable degree of difference in the S1 domain in the S1 domain between the bat SL-CoV Rp3 strain and SARS-CoV2.
T234 27192-27305 Sentence denotes A short-term moderate dose of IVIG combined with moderate-dose of corticosteroids might improve patient outcomes.
T235 27306-27537 Sentence denotes Studies show that the viral RNA of SARS-CoV2 reaches its peak during the first week and then gradually decreases and that IgG and IgM begin to rise from the 10th day so that most patients have anti-viral antibodies by the 14th day.
T236 27538-27669 Sentence denotes Passive immunization protects against disease, and so it should be administered as early as possible when the patient is diagnosed.
T237 27670-27730 Sentence denotes Evidence links COVID-19 to variable degrees of inflammation.
T238 27731-27787 Sentence denotes Corticosteroids offer a potent anti-inflammatory option.
T239 27788-27900 Sentence denotes However, they do not dictate precise actions and might cause suppression of anti-viral immune responses as well.
T240 27901-27986 Sentence denotes Studies show that the use of corticosteroids might accelerate recovery from COVID-19.
T241 27987-28106 Sentence denotes There are no controlled clinical trials that show whether the use of corticosteroids can reduce COVID-19-related death.
T242 28107-28286 Sentence denotes Moreover, the pro-inflammatory cytokine IL6 is the best-documented cytokine in COVID-19 correlated with severity, criticality, viral load, and prognosis of patients with COVID-19.
T243 28287-28398 Sentence denotes Tocilizumab, a monoclonal antibody against IL6, could confer clinical benefit in patients with high IL6 levels.