PMC:7258756 / 31689-38285 JSON TXT

Annnotations TAB JSON ListView MergeView

LitCovid-PubTator

LitCovid-PD-FMA-UBERON

LitCovid-PD-UBERON

{"project":"LitCovid-PD-UBERON","denotations":[{"id":"T7","span":{"begin":781,"end":787},"obj":"Body_part"},{"id":"T8","span":{"begin":789,"end":794},"obj":"Body_part"},{"id":"T9","span":{"begin":799,"end":804},"obj":"Body_part"},{"id":"T10","span":{"begin":948,"end":954},"obj":"Body_part"},{"id":"T11","span":{"begin":1120,"end":1126},"obj":"Body_part"},{"id":"T12","span":{"begin":1174,"end":1180},"obj":"Body_part"}],"attributes":[{"id":"A7","pred":"uberon_id","subj":"T7","obj":"http://purl.obolibrary.org/obo/UBERON_0007311"},{"id":"A8","pred":"uberon_id","subj":"T8","obj":"http://purl.obolibrary.org/obo/UBERON_0001088"},{"id":"A9","pred":"uberon_id","subj":"T9","obj":"http://purl.obolibrary.org/obo/UBERON_0001988"},{"id":"A10","pred":"uberon_id","subj":"T10","obj":"http://purl.obolibrary.org/obo/UBERON_0007311"},{"id":"A11","pred":"uberon_id","subj":"T11","obj":"http://purl.obolibrary.org/obo/UBERON_0001836"},{"id":"A12","pred":"uberon_id","subj":"T12","obj":"http://purl.obolibrary.org/obo/UBERON_0001836"}],"text":"Discussion\nTill February 29, 2020, three positive cases of SARS-CoV-2 were reported from India from 881 suspected cases tested at ICMR-NIV, Pune. All the three cases had a travel history from Wuhan, China, during January 2020. Although NGS was performed on the specimens for all the three positive cases, the complete genome sequence could be retrieved only from case 1 and case 3. The three cases were recovered after hospitalization and were home quarantined as per the guidelines of the Ministry of Health and Family Welfare, Government of India14.\nThe low viral copy number of the TS specimen from case 2 could be the possible reason for lesser viral reads being retrieved during the NGS run, leading to a fragmented genome. The recent study from China on serial samples (TSs, sputum, urine and stool) from two patients followed days 3-12 and days 4-15 post onset20. N gene-specific real-time RT-PCR assay showed that the viral loads in TS and sputum samples peaked at around 5-6 days after symptom onset, ranging from around 104-107 copies per ml during this time20. In another study, the virus was detected in the saliva specimens of 11 of the 12 patients, and serial saliva testing showed declines of viral RNA levels21.\nThe two Indian SARS-CoV-2 sequences were found to be non-identical (0.04% nt divergence), and the result of phylogenetic analysis indicated that there were two different introductions into the country. A recent study using 52 published GenBank sequences showed evidence of substantial genetic heterogeneity and estimated the time to the most recent common ancestor to be December 5, 2019 (95% confidence interval: November 6 - December 13, 2019)22. Continuous monitoring and analysis of the sequences from the affected countries would be vital to understand the genetic evolution and rates of substitution of the SARS-CoV-2.\nThe comparison of the amino acid sequences of the non-structural (nsp1-nsp16) and structural polyproteins was undertaken with reference to the Wuhan-Hu1 strain for molecular characterization. Some human Betacoronaviruses, including HCoV-HKU1 (lineage A), have a polybasic cleavage site as well as predicted O-linked glycans near the S1/S2 cleavage site of the spike protein. As published recently, the polybasic cleavage site that has not been previously observed in related lineage B Betacoronaviruses and is a unique feature of SARS-CoV-2 was noted in the Indian SARS-CoV-2. The mutation Arg408Ile in the spike protein of one of the Indian sequences is noted to be in the RBD and Ala930Val, is located in the S2 domain. However, both are away from the ACE2 receptor-binding interface1923. Mutations in the spike protein sequences of SARS-CoV-2 observed currently are localized over the S1 and S2 domains and, so far have not been found in the ACE2-binding interface.\nFrom the alignment of the spike protein sequences of SARS CoV-1 and SARS-CoV-2 (Wuhan-Hu1 and India), it can be observed that the three nucleotide-deletion in the case 1 SARS-CoV-2 from India, is located close to the insert 1 region of the SARS CoV-1 (Supplementary Fig. 3 (available from http://www.ijmr.org.in/articles/2020/151/2/images/IndianJMedRes_2020_151_2_200_281471_sm11.pdf)). Notably, case 1 and case 2 were in close contact while travelling to India, but due to the absence of the complete genome of case 2, the genetic relatedness and source of infection could not be pinpointed.\nAmong the SARS-CoV structural proteins, the spike protein has been found to elicit neutralizing antibodies24. In this study, it was observed that of the five B-cell linear epitopes, which were predicted, four epitopes were present in the S1 domain and one in the S2 domain. Prediction of conformational B-cell epitopes revealed that one of these (residue positions 341-505) in the spike protein incorporates two of the predicted linear epitopes (327-342 and 404-419) having good antigenicity along with a favourable IFN-γ response that enables differentiation and proliferation of the B-cells25. Notably, an equivalent epitope (347-499) is predicted for the model generated using the SARS-CoV-1 S protein as a template. In both cases, this epitope lies within the RBD6. Although the epitope has two putative N-linked glycosylation sites within it at positions 330 and 332, the probability of these sites being actually glycosylated is very low. A major immuno-dominant epitope has been reported from SARS-CoV between residues 441 and 70026. Hence, the predicted B-cell conformational epitope identified in the present study may play an important role in initiating a B-cell response. Among the five linear epitopes predicted in this study, epitopes 327-342 and 1204-1219 are conserved between SARS-CoV-2 and SARS-CoV-1. Epitopes 243-258, 404-419 and 413-428 are found to have variations.\nThe spike protein of SARS-CoV has also been reported to be immunogenic and elicit high IFN-γ-specific T-cell response26. The prediction results in this study revealed that nine possible CTL epitopes possessing good antigenicity and inducing IFN-γ response were present in the S protein. A recent report27 also predicted T-cell epitopes in the S protein based on a similar ANN/SVM method and antigenicity score. Although the IFN-γ response was not considered by these authors, it was noted that two of the predictions were found to be common. Among the T-cell epitopes predicted in the present study, four epitopes 89-97 and 256-264 in the S1 domain and 825-833 and 1058-1066 in the S2 domain were found to have good CTL prediction scores with a broad HLA allele coverage of A and B supertypes. These HLA supertypes being predominant in the Indian population, the predicted epitopes may be considered suitable for future experiments towards vaccine design.\nTo conclude, the prompt intervention by the Government of India and the health authorities of the State of Kerala, ensured that the said cases did not become secondary foci of transmission. Further, the timely identification of SARS-CoV-2 in these suspected cases by the ICMR-NIV, Pune, has helped in the isolation of the patients, containment and enhanced surveillances for the virus and its restricted movement. The availability of the genomic sequences of the identified cases will contribute to the public repositories and help towards the development of diagnostics, vaccines and antivirals. The sequence data would also help in tracking the virus from its origin and evolution with its transmission in time.\nAvailability of data: Sequences are deposited in GISAID database, with accession numbers EPI ISL 413522 and EPI ISL 413523."}

LitCovid-PD-MONDO

LitCovid-PD-CLO

LitCovid-PD-CHEBI

LitCovid-PD-GO-BP

{"project":"LitCovid-PD-GO-BP","denotations":[{"id":"T26","span":{"begin":4223,"end":4245},"obj":"http://purl.obolibrary.org/obo/GO_0006487"},{"id":"T27","span":{"begin":4232,"end":4245},"obj":"http://purl.obolibrary.org/obo/GO_0070085"}],"text":"Discussion\nTill February 29, 2020, three positive cases of SARS-CoV-2 were reported from India from 881 suspected cases tested at ICMR-NIV, Pune. All the three cases had a travel history from Wuhan, China, during January 2020. Although NGS was performed on the specimens for all the three positive cases, the complete genome sequence could be retrieved only from case 1 and case 3. The three cases were recovered after hospitalization and were home quarantined as per the guidelines of the Ministry of Health and Family Welfare, Government of India14.\nThe low viral copy number of the TS specimen from case 2 could be the possible reason for lesser viral reads being retrieved during the NGS run, leading to a fragmented genome. The recent study from China on serial samples (TSs, sputum, urine and stool) from two patients followed days 3-12 and days 4-15 post onset20. N gene-specific real-time RT-PCR assay showed that the viral loads in TS and sputum samples peaked at around 5-6 days after symptom onset, ranging from around 104-107 copies per ml during this time20. In another study, the virus was detected in the saliva specimens of 11 of the 12 patients, and serial saliva testing showed declines of viral RNA levels21.\nThe two Indian SARS-CoV-2 sequences were found to be non-identical (0.04% nt divergence), and the result of phylogenetic analysis indicated that there were two different introductions into the country. A recent study using 52 published GenBank sequences showed evidence of substantial genetic heterogeneity and estimated the time to the most recent common ancestor to be December 5, 2019 (95% confidence interval: November 6 - December 13, 2019)22. Continuous monitoring and analysis of the sequences from the affected countries would be vital to understand the genetic evolution and rates of substitution of the SARS-CoV-2.\nThe comparison of the amino acid sequences of the non-structural (nsp1-nsp16) and structural polyproteins was undertaken with reference to the Wuhan-Hu1 strain for molecular characterization. Some human Betacoronaviruses, including HCoV-HKU1 (lineage A), have a polybasic cleavage site as well as predicted O-linked glycans near the S1/S2 cleavage site of the spike protein. As published recently, the polybasic cleavage site that has not been previously observed in related lineage B Betacoronaviruses and is a unique feature of SARS-CoV-2 was noted in the Indian SARS-CoV-2. The mutation Arg408Ile in the spike protein of one of the Indian sequences is noted to be in the RBD and Ala930Val, is located in the S2 domain. However, both are away from the ACE2 receptor-binding interface1923. Mutations in the spike protein sequences of SARS-CoV-2 observed currently are localized over the S1 and S2 domains and, so far have not been found in the ACE2-binding interface.\nFrom the alignment of the spike protein sequences of SARS CoV-1 and SARS-CoV-2 (Wuhan-Hu1 and India), it can be observed that the three nucleotide-deletion in the case 1 SARS-CoV-2 from India, is located close to the insert 1 region of the SARS CoV-1 (Supplementary Fig. 3 (available from http://www.ijmr.org.in/articles/2020/151/2/images/IndianJMedRes_2020_151_2_200_281471_sm11.pdf)). Notably, case 1 and case 2 were in close contact while travelling to India, but due to the absence of the complete genome of case 2, the genetic relatedness and source of infection could not be pinpointed.\nAmong the SARS-CoV structural proteins, the spike protein has been found to elicit neutralizing antibodies24. In this study, it was observed that of the five B-cell linear epitopes, which were predicted, four epitopes were present in the S1 domain and one in the S2 domain. Prediction of conformational B-cell epitopes revealed that one of these (residue positions 341-505) in the spike protein incorporates two of the predicted linear epitopes (327-342 and 404-419) having good antigenicity along with a favourable IFN-γ response that enables differentiation and proliferation of the B-cells25. Notably, an equivalent epitope (347-499) is predicted for the model generated using the SARS-CoV-1 S protein as a template. In both cases, this epitope lies within the RBD6. Although the epitope has two putative N-linked glycosylation sites within it at positions 330 and 332, the probability of these sites being actually glycosylated is very low. A major immuno-dominant epitope has been reported from SARS-CoV between residues 441 and 70026. Hence, the predicted B-cell conformational epitope identified in the present study may play an important role in initiating a B-cell response. Among the five linear epitopes predicted in this study, epitopes 327-342 and 1204-1219 are conserved between SARS-CoV-2 and SARS-CoV-1. Epitopes 243-258, 404-419 and 413-428 are found to have variations.\nThe spike protein of SARS-CoV has also been reported to be immunogenic and elicit high IFN-γ-specific T-cell response26. The prediction results in this study revealed that nine possible CTL epitopes possessing good antigenicity and inducing IFN-γ response were present in the S protein. A recent report27 also predicted T-cell epitopes in the S protein based on a similar ANN/SVM method and antigenicity score. Although the IFN-γ response was not considered by these authors, it was noted that two of the predictions were found to be common. Among the T-cell epitopes predicted in the present study, four epitopes 89-97 and 256-264 in the S1 domain and 825-833 and 1058-1066 in the S2 domain were found to have good CTL prediction scores with a broad HLA allele coverage of A and B supertypes. These HLA supertypes being predominant in the Indian population, the predicted epitopes may be considered suitable for future experiments towards vaccine design.\nTo conclude, the prompt intervention by the Government of India and the health authorities of the State of Kerala, ensured that the said cases did not become secondary foci of transmission. Further, the timely identification of SARS-CoV-2 in these suspected cases by the ICMR-NIV, Pune, has helped in the isolation of the patients, containment and enhanced surveillances for the virus and its restricted movement. The availability of the genomic sequences of the identified cases will contribute to the public repositories and help towards the development of diagnostics, vaccines and antivirals. The sequence data would also help in tracking the virus from its origin and evolution with its transmission in time.\nAvailability of data: Sequences are deposited in GISAID database, with accession numbers EPI ISL 413522 and EPI ISL 413523."}

LitCovid-sentences

2_test

{"project":"2_test","denotations":[{"id":"32242873-31950516-47036570","span":{"begin":1030,"end":1033},"obj":"31950516"},{"id":"32242873-31138817-47036571","span":{"begin":2638,"end":2642},"obj":"31138817"},{"id":"32242873-15210961-47036572","span":{"begin":3521,"end":3523},"obj":"15210961"},{"id":"32242873-9916700-47036573","span":{"begin":4007,"end":4009},"obj":"9916700"},{"id":"32242873-32007145-47036574","span":{"begin":4182,"end":4183},"obj":"32007145"},{"id":"32242873-26038429-47036575","span":{"begin":4449,"end":4454},"obj":"26038429"},{"id":"32242873-26038429-47036576","span":{"begin":4920,"end":4922},"obj":"26038429"},{"id":"32242873-32022276-47036577","span":{"begin":5105,"end":5107},"obj":"32022276"},{"id":"T37244","span":{"begin":1030,"end":1033},"obj":"31950516"},{"id":"T1135","span":{"begin":2638,"end":2642},"obj":"31138817"},{"id":"T80103","span":{"begin":3521,"end":3523},"obj":"15210961"},{"id":"T68904","span":{"begin":4007,"end":4009},"obj":"9916700"},{"id":"T89340","span":{"begin":4182,"end":4183},"obj":"32007145"},{"id":"T29055","span":{"begin":4449,"end":4454},"obj":"26038429"},{"id":"T63478","span":{"begin":4920,"end":4922},"obj":"26038429"},{"id":"T36379","span":{"begin":5105,"end":5107},"obj":"32022276"}],"text":"Discussion\nTill February 29, 2020, three positive cases of SARS-CoV-2 were reported from India from 881 suspected cases tested at ICMR-NIV, Pune. All the three cases had a travel history from Wuhan, China, during January 2020. Although NGS was performed on the specimens for all the three positive cases, the complete genome sequence could be retrieved only from case 1 and case 3. The three cases were recovered after hospitalization and were home quarantined as per the guidelines of the Ministry of Health and Family Welfare, Government of India14.\nThe low viral copy number of the TS specimen from case 2 could be the possible reason for lesser viral reads being retrieved during the NGS run, leading to a fragmented genome. The recent study from China on serial samples (TSs, sputum, urine and stool) from two patients followed days 3-12 and days 4-15 post onset20. N gene-specific real-time RT-PCR assay showed that the viral loads in TS and sputum samples peaked at around 5-6 days after symptom onset, ranging from around 104-107 copies per ml during this time20. In another study, the virus was detected in the saliva specimens of 11 of the 12 patients, and serial saliva testing showed declines of viral RNA levels21.\nThe two Indian SARS-CoV-2 sequences were found to be non-identical (0.04% nt divergence), and the result of phylogenetic analysis indicated that there were two different introductions into the country. A recent study using 52 published GenBank sequences showed evidence of substantial genetic heterogeneity and estimated the time to the most recent common ancestor to be December 5, 2019 (95% confidence interval: November 6 - December 13, 2019)22. Continuous monitoring and analysis of the sequences from the affected countries would be vital to understand the genetic evolution and rates of substitution of the SARS-CoV-2.\nThe comparison of the amino acid sequences of the non-structural (nsp1-nsp16) and structural polyproteins was undertaken with reference to the Wuhan-Hu1 strain for molecular characterization. Some human Betacoronaviruses, including HCoV-HKU1 (lineage A), have a polybasic cleavage site as well as predicted O-linked glycans near the S1/S2 cleavage site of the spike protein. As published recently, the polybasic cleavage site that has not been previously observed in related lineage B Betacoronaviruses and is a unique feature of SARS-CoV-2 was noted in the Indian SARS-CoV-2. The mutation Arg408Ile in the spike protein of one of the Indian sequences is noted to be in the RBD and Ala930Val, is located in the S2 domain. However, both are away from the ACE2 receptor-binding interface1923. Mutations in the spike protein sequences of SARS-CoV-2 observed currently are localized over the S1 and S2 domains and, so far have not been found in the ACE2-binding interface.\nFrom the alignment of the spike protein sequences of SARS CoV-1 and SARS-CoV-2 (Wuhan-Hu1 and India), it can be observed that the three nucleotide-deletion in the case 1 SARS-CoV-2 from India, is located close to the insert 1 region of the SARS CoV-1 (Supplementary Fig. 3 (available from http://www.ijmr.org.in/articles/2020/151/2/images/IndianJMedRes_2020_151_2_200_281471_sm11.pdf)). Notably, case 1 and case 2 were in close contact while travelling to India, but due to the absence of the complete genome of case 2, the genetic relatedness and source of infection could not be pinpointed.\nAmong the SARS-CoV structural proteins, the spike protein has been found to elicit neutralizing antibodies24. In this study, it was observed that of the five B-cell linear epitopes, which were predicted, four epitopes were present in the S1 domain and one in the S2 domain. Prediction of conformational B-cell epitopes revealed that one of these (residue positions 341-505) in the spike protein incorporates two of the predicted linear epitopes (327-342 and 404-419) having good antigenicity along with a favourable IFN-γ response that enables differentiation and proliferation of the B-cells25. Notably, an equivalent epitope (347-499) is predicted for the model generated using the SARS-CoV-1 S protein as a template. In both cases, this epitope lies within the RBD6. Although the epitope has two putative N-linked glycosylation sites within it at positions 330 and 332, the probability of these sites being actually glycosylated is very low. A major immuno-dominant epitope has been reported from SARS-CoV between residues 441 and 70026. Hence, the predicted B-cell conformational epitope identified in the present study may play an important role in initiating a B-cell response. Among the five linear epitopes predicted in this study, epitopes 327-342 and 1204-1219 are conserved between SARS-CoV-2 and SARS-CoV-1. Epitopes 243-258, 404-419 and 413-428 are found to have variations.\nThe spike protein of SARS-CoV has also been reported to be immunogenic and elicit high IFN-γ-specific T-cell response26. The prediction results in this study revealed that nine possible CTL epitopes possessing good antigenicity and inducing IFN-γ response were present in the S protein. A recent report27 also predicted T-cell epitopes in the S protein based on a similar ANN/SVM method and antigenicity score. Although the IFN-γ response was not considered by these authors, it was noted that two of the predictions were found to be common. Among the T-cell epitopes predicted in the present study, four epitopes 89-97 and 256-264 in the S1 domain and 825-833 and 1058-1066 in the S2 domain were found to have good CTL prediction scores with a broad HLA allele coverage of A and B supertypes. These HLA supertypes being predominant in the Indian population, the predicted epitopes may be considered suitable for future experiments towards vaccine design.\nTo conclude, the prompt intervention by the Government of India and the health authorities of the State of Kerala, ensured that the said cases did not become secondary foci of transmission. Further, the timely identification of SARS-CoV-2 in these suspected cases by the ICMR-NIV, Pune, has helped in the isolation of the patients, containment and enhanced surveillances for the virus and its restricted movement. The availability of the genomic sequences of the identified cases will contribute to the public repositories and help towards the development of diagnostics, vaccines and antivirals. The sequence data would also help in tracking the virus from its origin and evolution with its transmission in time.\nAvailability of data: Sequences are deposited in GISAID database, with accession numbers EPI ISL 413522 and EPI ISL 413523."}

PMC:7258756 / 31689-38285 JSONTXT

Annnotations TAB JSON ListView MergeView

PMC:7258756 / 31689-38285 JSON TXT