Id |
Subject |
Object |
Predicate |
Lexical cue |
T59 |
0-22 |
Sentence |
denotes |
THE VIRUS (SARS-CoV-2) |
T60 |
23-164 |
Sentence |
denotes |
Coronaviruses are positive-sense RNA viruses having an extensive and promiscuous range of natural hosts and affect multiple systems (23, 24). |
T61 |
165-319 |
Sentence |
denotes |
Coronaviruses can cause clinical diseases in humans that may extend from the common cold to more severe respiratory diseases like SARS and MERS (17, 279). |
T62 |
320-586 |
Sentence |
denotes |
The recently emerging SARS-CoV-2 has wrought havoc in China and caused a pandemic situation in the worldwide population, leading to disease outbreaks that have not been controlled to date, although extensive efforts are being put in place to counter this virus (25). |
T63 |
587-917 |
Sentence |
denotes |
This virus has been proposed to be designated/named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses (ICTV), which determined the virus belongs to the Severe acute respiratory syndrome-related coronavirus category and found this virus is related to SARS-CoVs (26). |
T64 |
918-1145 |
Sentence |
denotes |
SARS-CoV-2 is a member of the order Nidovirales, family Coronaviridae, subfamily Orthocoronavirinae, which is subdivided into four genera, viz., Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus (3, 27). |
T65 |
1146-1321 |
Sentence |
denotes |
The genera Alphacoronavirus and Betacoronavirus originate from bats, while Gammacoronavirus and Deltacoronavirus have evolved from bird and swine gene pools (24, 28, 29, 275). |
T66 |
1322-1466 |
Sentence |
denotes |
Coronaviruses possess an unsegmented, single-stranded, positive-sense RNA genome of around 30 kb, enclosed by a 5′-cap and 3′-poly(A) tail (30). |
T67 |
1467-1542 |
Sentence |
denotes |
The genome of SARS-CoV-2 is 29,891 bp long, with a G+C content of 38% (31). |
T68 |
1543-1618 |
Sentence |
denotes |
These viruses are encircled with an envelope containing viral nucleocapsid. |
T69 |
1619-1751 |
Sentence |
denotes |
The nucleocapsids in CoVs are arranged in helical symmetry, which reflects an atypical attribute in positive-sense RNA viruses (30). |
T70 |
1752-1997 |
Sentence |
denotes |
The electron micrographs of SARS-CoV-2 revealed a diverging spherical outline with some degree of pleomorphism, virion diameters varying from 60 to 140 nm, and distinct spikes of 9 to 12 nm, giving the virus the appearance of a solar corona (3). |
T71 |
1998-2108 |
Sentence |
denotes |
The CoV genome is arranged linearly as 5′-leader-UTR-replicase-structural genes (S-E-M-N)-3′ UTR-poly(A) (32). |
T72 |
2109-2246 |
Sentence |
denotes |
Accessory genes, such as 3a/b, 4a/b, and the hemagglutinin-esterase gene (HE), are also seen intermingled with the structural genes (30). |
T73 |
2247-2424 |
Sentence |
denotes |
SARS-CoV-2 has also been found to be arranged similarly and encodes several accessory proteins, although it lacks the HE, which is characteristic of some betacoronaviruses (31). |
T74 |
2425-2534 |
Sentence |
denotes |
The positive-sense genome of CoVs serves as the mRNA and is translated to polyprotein 1a/1ab (pp1a/1ab) (33). |
T75 |
2535-2693 |
Sentence |
denotes |
A replication-transcription complex (RTC) is formed in double-membrane vesicles (DMVs) by nonstructural proteins (nsps), encoded by the polyprotein gene (34). |
T76 |
2694-2806 |
Sentence |
denotes |
Subsequently, the RTC synthesizes a nested set of subgenomic RNAs (sgRNAs) via discontinuous transcription (35). |
T77 |
2807-2934 |
Sentence |
denotes |
Based on molecular characterization, SARS-CoV-2 is considered a new Betacoronavirus belonging to the subgenus Sarbecovirus (3). |
T78 |
2935-3038 |
Sentence |
denotes |
A few other critical zoonotic viruses (MERS-related CoV and SARS-related CoV) belong to the same genus. |
T79 |
3039-3222 |
Sentence |
denotes |
However, SARS-CoV-2 was identified as a distinct virus based on the percent identity with other Betacoronavirus; conserved open reading frame 1a/b (ORF1a/b) is below 90% identity (3). |
T80 |
3223-3399 |
Sentence |
denotes |
An overall 80% nucleotide identity was observed between SARS-CoV-2 and the original SARS-CoV, along with 89% identity with ZC45 and ZXC21 SARS-related CoVs of bats (2, 31, 36). |
T81 |
3400-3521 |
Sentence |
denotes |
In addition, 82% identity has been observed between SARS-CoV-2 and human SARS-CoV Tor2 and human SARS-CoV BJ01 2003 (31). |
T82 |
3522-3635 |
Sentence |
denotes |
A sequence identity of only 51.8% was observed between MERS-related CoV and the recently emerged SARS-CoV-2 (37). |
T83 |
3636-3746 |
Sentence |
denotes |
Phylogenetic analysis of the structural genes also revealed that SARS-CoV-2 is closer to bat SARS-related CoV. |
T84 |
3747-3894 |
Sentence |
denotes |
Therefore, SARS-CoV-2 might have originated from bats, while other amplifier hosts might have played a role in disease transmission to humans (31). |
T85 |
3895-4007 |
Sentence |
denotes |
Of note, the other two zoonotic CoVs (MERS-related CoV and SARS-related CoV) also originated from bats (38, 39). |
T86 |
4008-4109 |
Sentence |
denotes |
Nevertheless, for SARS and MERS, civet cat and camels, respectively, act as amplifier hosts (40, 41). |
T87 |
4110-4166 |
Sentence |
denotes |
Coronavirus genomes and subgenomes encode six ORFs (31). |
T88 |
4167-4241 |
Sentence |
denotes |
The majority of the 5′ end is occupied by ORF1a/b, which produces 16 nsps. |
T89 |
4242-4364 |
Sentence |
denotes |
The two polyproteins, pp1a and pp1ab, are initially produced from ORF1a/b by a −1 frameshift between ORF1a and ORF1b (32). |
T90 |
4365-4533 |
Sentence |
denotes |
The virus-encoded proteases cleave polyproteins into individual nsps (main protease [Mpro], chymotrypsin-like protease [3CLpro], and papain-like proteases [PLPs]) (42). |
T91 |
4534-4625 |
Sentence |
denotes |
SARS-CoV-2 also encodes these nsps, and their functions have been elucidated recently (31). |
T92 |
4626-4855 |
Sentence |
denotes |
Remarkably, a difference between SARS-CoV-2 and other CoVs is the identification of a novel short putative protein within the ORF3 band, a secreted protein with an alpha helix and beta-sheet with six strands encoded by ORF8 (31). |
T93 |
4856-5014 |
Sentence |
denotes |
Coronaviruses encode four major structural proteins, namely, spike (S), membrane (M), envelope (E), and nucleocapsid (N), which are described in detail below. |
T94 |
5016-5030 |
Sentence |
denotes |
S Glycoprotein |
T95 |
5031-5117 |
Sentence |
denotes |
Coronavirus S protein is a large, multifunctional class I viral transmembrane protein. |
T96 |
5118-5284 |
Sentence |
denotes |
The size of this abundant S protein varies from 1,160 amino acids (IBV, infectious bronchitis virus, in poultry) to 1,400 amino acids (FCoV, feline coronavirus) (43). |
T97 |
5285-5380 |
Sentence |
denotes |
It lies in a trimer on the virion surface, giving the virion a corona or crown-like appearance. |
T98 |
5381-5534 |
Sentence |
denotes |
Functionally it is required for the entry of the infectious virion particles into the cell through interaction with various host cellular receptors (44). |
T99 |
5535-5637 |
Sentence |
denotes |
Furthermore, it acts as a critical factor for tissue tropism and the determination of host range (45). |
T100 |
5638-5756 |
Sentence |
denotes |
Notably, S protein is one of the vital immunodominant proteins of CoVs capable of inducing host immune responses (45). |
T101 |
5757-5873 |
Sentence |
denotes |
The ectodomains in all CoVs S proteins have similar domain organizations, divided into two subunits, S1 and S2 (43). |
T102 |
5874-5971 |
Sentence |
denotes |
The first one, S1, helps in host receptor binding, while the second one, S2, accounts for fusion. |
T103 |
5972-6092 |
Sentence |
denotes |
The former (S1) is further divided into two subdomains, namely, the N-terminal domain (NTD) and C-terminal domain (CTD). |
T104 |
6093-6208 |
Sentence |
denotes |
Both of these subdomains act as receptor-binding domains, interacting efficiently with various host receptors (45). |
T105 |
6209-6262 |
Sentence |
denotes |
The S1 CTD contains the receptor-binding motif (RBM). |
T106 |
6263-6366 |
Sentence |
denotes |
In each coronavirus spike protein, the trimeric S1 locates itself on top of the trimeric S2 stalk (45). |
T107 |
6367-6508 |
Sentence |
denotes |
Recently, structural analyses of the S proteins of COVID-19 have revealed 27 amino acid substitutions within a 1,273-amino-acid stretch (16). |
T108 |
6509-6649 |
Sentence |
denotes |
Six substitutions are located in the RBD (amino acids 357 to 528), while four substitutions are in the RBM at the CTD of the S1 domain (16). |
T109 |
6650-6797 |
Sentence |
denotes |
Of note, no amino acid change is seen in the RBM, which binds directly to the angiotensin-converting enzyme-2 (ACE2) receptor in SARS-CoV (16, 46). |
T110 |
6798-6905 |
Sentence |
denotes |
At present, the main emphasis is knowing how many differences would be required to change the host tropism. |
T111 |
6906-7036 |
Sentence |
denotes |
Sequence comparison revealed 17 nonsynonymous changes between the early sequence of SARS-CoV-2 and the later isolates of SARS-CoV. |
T112 |
7037-7229 |
Sentence |
denotes |
The changes were found scattered over the genome of the virus, with nine substitutions in ORF1ab, ORF8 (4 substitutions), the spike gene (3 substitutions), and ORF7a (single substitution) (4). |
T113 |
7230-7394 |
Sentence |
denotes |
Notably, the same nonsynonymous changes were found in a familial cluster, indicating that the viral evolution happened during person-to-person transmission (4, 47). |
T114 |
7395-7527 |
Sentence |
denotes |
Such adaptive evolution events are frequent and constitute a constantly ongoing process once the virus spreads among new hosts (47). |
T115 |
7528-7732 |
Sentence |
denotes |
Even though no functional changes occur in the virus associated with this adaptive evolution, close monitoring of the viral mutations that occur during subsequent human-to-human transmission is warranted. |
T116 |
7734-7743 |
Sentence |
denotes |
M Protein |
T117 |
7744-7876 |
Sentence |
denotes |
The M protein is the most abundant viral protein present in the virion particle, giving a definite shape to the viral envelope (48). |
T118 |
7877-7967 |
Sentence |
denotes |
It binds to the nucleocapsid and acts as a central organizer of coronavirus assembly (49). |
T119 |
7968-8105 |
Sentence |
denotes |
Coronavirus M proteins are highly diverse in amino acid contents but maintain overall structural similarity within different genera (50). |
T120 |
8106-8257 |
Sentence |
denotes |
The M protein has three transmembrane domains, flanked by a short amino terminus outside the virion and a long carboxy terminus inside the virion (50). |
T121 |
8258-8319 |
Sentence |
denotes |
Overall, the viral scaffold is maintained by M-M interaction. |
T122 |
8320-8432 |
Sentence |
denotes |
Of note, the M protein of SARS-CoV-2 does not have an amino acid substitution compared to that of SARS-CoV (16). |
T123 |
8434-8443 |
Sentence |
denotes |
E Protein |
T124 |
8444-8543 |
Sentence |
denotes |
The coronavirus E protein is the most enigmatic and smallest of the major structural proteins (51). |
T125 |
8544-8637 |
Sentence |
denotes |
It plays a multifunctional role in the pathogenesis, assembly, and release of the virus (52). |
T126 |
8638-8726 |
Sentence |
denotes |
It is a small integral membrane polypeptide that acts as a viroporin (ion channel) (53). |
T127 |
8727-8870 |
Sentence |
denotes |
The inactivation or absence of this protein is related to the altered virulence of coronaviruses due to changes in morphology and tropism (54). |
T128 |
8871-9038 |
Sentence |
denotes |
The E protein consists of three domains, namely, a short hydrophilic amino terminal, a large hydrophobic transmembrane domain, and an efficient C-terminal domain (51). |
T129 |
9039-9136 |
Sentence |
denotes |
The SARS-CoV-2 E protein reveals a similar amino acid constitution without any substitution (16). |
T130 |
9138-9147 |
Sentence |
denotes |
N Protein |
T131 |
9148-9193 |
Sentence |
denotes |
The N protein of coronavirus is multipurpose. |
T132 |
9194-9408 |
Sentence |
denotes |
Among several functions, it plays a role in complex formation with the viral genome, facilitates M protein interaction needed during virion assembly, and enhances the transcription efficiency of the virus (55, 56). |
T133 |
9409-9545 |
Sentence |
denotes |
It contains three highly conserved and distinct domains, namely, an NTD, an RNA-binding domain or a linker region (LKR), and a CTD (57). |
T134 |
9546-9693 |
Sentence |
denotes |
The NTD binds with the 3′ end of the viral genome, perhaps via electrostatic interactions, and is highly diverged both in length and sequence (58). |
T135 |
9694-9800 |
Sentence |
denotes |
The charged LKR is serine and arginine rich and is also known as the SR (serine and arginine) domain (59). |
T136 |
9801-9919 |
Sentence |
denotes |
The LKR is capable of direct interaction with in vitro RNA interaction and is responsible for cell signaling (60, 61). |
T137 |
9920-10048 |
Sentence |
denotes |
It also modulates the antiviral response of the host by working as an antagonist for interferon (IFN) and RNA interference (62). |
T138 |
10049-10306 |
Sentence |
denotes |
Compared to that of SARS-CoV, the N protein of SARS-CoV-2 possess five amino acid mutations, where two are in the intrinsically dispersed region (IDR; positions 25 and 26), one each in the NTD (position 103), LKR (position 217), and CTD (position 334) (16). |
T139 |
10308-10335 |
Sentence |
denotes |
nsps and Accessory Proteins |
T140 |
10336-10523 |
Sentence |
denotes |
Besides the important structural proteins, the SARS-CoV-2 genome contains 15 nsps, nsp1 to nsp10 and nsp12 to nsp16, and 8 accessory proteins (3a, 3b, p6, 7a, 7b, 8b, 9b, and ORF14) (16). |
T141 |
10524-10590 |
Sentence |
denotes |
All these proteins play a specific role in viral replication (27). |
T142 |
10591-10721 |
Sentence |
denotes |
Unlike the accessory proteins of SARS-CoV, SARS-CoV-2 does not contain 8a protein and has a longer 8b and shorter 3b protein (16). |
T143 |
10722-10901 |
Sentence |
denotes |
The nsp7, nsp13, envelope, matrix, and p6 and 8b accessory proteins have not been detected with any amino acid substitutions compared to the sequences of other coronaviruses (16). |
T144 |
10902-10958 |
Sentence |
denotes |
The virus structure of SARS-CoV-2 is depicted in Fig. 2. |
T145 |
10959-10993 |
Sentence |
denotes |
FIG 2 SARS-CoV-2 virus structure. |
T146 |
10995-11038 |
Sentence |
denotes |
SARS-CoV-2 Spike Glycoprotein Gene Analysis |
T147 |
11040-11077 |
Sentence |
denotes |
Sequence percent similarity analysis. |
T148 |
11078-11254 |
Sentence |
denotes |
We assessed the nucleotide percent similarity using the MegAlign software program, where the similarity between the novel SARS-CoV-2 isolates was in the range of 99.4% to 100%. |
T149 |
11255-11442 |
Sentence |
denotes |
Among the other Serbecovirus CoV sequences, the novel SARS-CoV-2 sequences revealed the highest similarity to bat-SL-CoV, with nucleotide percent identity ranges between 88.12 and 89.65%. |
T150 |
11443-11551 |
Sentence |
denotes |
Meanwhile, earlier reported SARS-CoVs showed 70.6 to 74.9% similarity to SARS-CoV-2 at the nucleotide level. |
T151 |
11552-11764 |
Sentence |
denotes |
Further, the nucleotide percent similarity was 55.4%, 45.5% to 47.9%, 46.2% to 46.6%, and 45.0% to 46.3% to the other four subgenera, namely, Hibecovirus, Nobecovirus, Merbecovirus, and Embecovirus, respectively. |
T152 |
11765-11925 |
Sentence |
denotes |
The percent similarity index of current outbreak isolates indicates a close relationship between SARS-CoV-2 isolates and bat-SL-CoV, indicating a common origin. |
T153 |
11926-12216 |
Sentence |
denotes |
However, particular pieces of evidence based on further complete genomic analysis of current isolates are necessary to draw any conclusions, although it was ascertained that the current novel SARS-CoV-2 isolates belong to the subgenus Sarbecovirus in the diverse range of betacoronaviruses. |
T154 |
12217-12367 |
Sentence |
denotes |
Their possible ancestor was hypothesized to be from bat CoV strains, wherein bats might have played a crucial role in harboring this class of viruses. |
T155 |
12369-12399 |
Sentence |
denotes |
SplitsTree phylogeny analysis. |
T156 |
12400-12561 |
Sentence |
denotes |
In the unrooted phylogenetic tree of different betacoronaviruses based on the S protein, virus sequences from different subgenera grouped into separate clusters. |
T157 |
12562-12687 |
Sentence |
denotes |
SARS-CoV-2 sequences from Wuhan and other countries exhibited a close relationship and appeared in a single cluster (Fig. 1). |
T158 |
12688-12869 |
Sentence |
denotes |
The CoVs from the subgenus Sarbecovirus appeared jointly in SplitsTree and divided into three subclusters, namely, SARS-CoV-2, bat-SARS-like-CoV (bat-SL-CoV), and SARS-CoV (Fig. 1). |
T159 |
12870-13135 |
Sentence |
denotes |
In the case of other subgenera, like Merbecovirus, all of the sequences grouped in a single cluster, whereas in Embecovirus, different species, comprised of canine respiratory CoVs, bovine CoVs, equine CoVs, and human CoV strain (OC43), grouped in a common cluster. |
T160 |
13136-13284 |
Sentence |
denotes |
Isolates in the subgenera Nobecovorus and Hibecovirus were found to be placed separately away from other reported SARS-CoVs but shared a bat origin. |