PubMed:38755139 JSONTXT

{"project":"mondo_disease","denotations":[{"id":"T1","span":{"begin":61,"end":71},"obj":"Disease"},{"id":"T2","span":{"begin":206,"end":216},"obj":"Disease"},{"id":"T3","span":{"begin":245,"end":260},"obj":"Disease"},{"id":"T4","span":{"begin":472,"end":482},"obj":"Disease"},{"id":"T5","span":{"begin":615,"end":630},"obj":"Disease"},{"id":"T6","span":{"begin":817,"end":827},"obj":"Disease"},{"id":"T7","span":{"begin":1337,"end":1347},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MONDO_0005108"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/MONDO_0005108"},{"id":"A6","pred":"mondo_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A7","pred":"mondo_id","subj":"T7","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"}],"text":"Sequential glycosylations at the multibasic cleavage site of SARS-CoV-2 spike protein regulate viral activity.\nThe multibasic furin cleavage site at the S1/S2 boundary of the spike protein is a hallmark of SARS-CoV-2 and plays a crucial role in viral infection. However, the mechanism underlying furin activation and its regulation remain poorly understood. Here, we show that GalNAc-T3 and T7 jointly initiate clustered O-glycosylations in the furin cleavage site of the SARS-CoV-2 spike protein, which inhibit furin processing, suppress the incorporation of the spike protein into virus-like-particles and affect viral infection. Mechanistic analysis reveals that the assembly of the spike protein into virus-like particles relies on interactions between the furin-cleaved spike protein and the membrane protein of SARS-CoV-2, suggesting a possible mechanism for furin activation. Interestingly, mutations in the spike protein of the alpha and delta variants of the virus confer resistance against glycosylation by GalNAc-T3 and T7. In the omicron variant, additional mutations reverse this resistance, making the spike protein susceptible to glycosylation in vitro and sensitive to GalNAc-T3 and T7 expression in human lung cells. Our findings highlight the role of glycosylation as a defense mechanism employed by host cells against SARS-CoV-2 and shed light on the evolutionary interplay between the host and the virus."}

{"project":"GlyCosmos15-Glycan","denotations":[{"id":"T1","span":{"begin":377,"end":383},"obj":"Glycan"},{"id":"T2","span":{"begin":1017,"end":1023},"obj":"Glycan"},{"id":"T3","span":{"begin":1185,"end":1191},"obj":"Glycan"}],"attributes":[{"id":"A1","pred":"glycosmos_id","subj":"T1","obj":"https://glycosmos.org/glycans/show/G39738WL"},{"id":"A4","pred":"image","subj":"T1","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G39738WL"},{"id":"A2","pred":"glycosmos_id","subj":"T2","obj":"https://glycosmos.org/glycans/show/G39738WL"},{"id":"A5","pred":"image","subj":"T2","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G39738WL"},{"id":"A3","pred":"glycosmos_id","subj":"T3","obj":"https://glycosmos.org/glycans/show/G39738WL"},{"id":"A6","pred":"image","subj":"T3","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G39738WL"}],"text":"Sequential glycosylations at the multibasic cleavage site of SARS-CoV-2 spike protein regulate viral activity.\nThe multibasic furin cleavage site at the S1/S2 boundary of the spike protein is a hallmark of SARS-CoV-2 and plays a crucial role in viral infection. However, the mechanism underlying furin activation and its regulation remain poorly understood. Here, we show that GalNAc-T3 and T7 jointly initiate clustered O-glycosylations in the furin cleavage site of the SARS-CoV-2 spike protein, which inhibit furin processing, suppress the incorporation of the spike protein into virus-like-particles and affect viral infection. Mechanistic analysis reveals that the assembly of the spike protein into virus-like particles relies on interactions between the furin-cleaved spike protein and the membrane protein of SARS-CoV-2, suggesting a possible mechanism for furin activation. Interestingly, mutations in the spike protein of the alpha and delta variants of the virus confer resistance against glycosylation by GalNAc-T3 and T7. In the omicron variant, additional mutations reverse this resistance, making the spike protein susceptible to glycosylation in vitro and sensitive to GalNAc-T3 and T7 expression in human lung cells. Our findings highlight the role of glycosylation as a defense mechanism employed by host cells against SARS-CoV-2 and shed light on the evolutionary interplay between the host and the virus."}

{"project":"Glycan-GlyCosmos","denotations":[{"id":"T1","span":{"begin":377,"end":383},"obj":"Glycan"},{"id":"T2","span":{"begin":1017,"end":1023},"obj":"Glycan"},{"id":"T3","span":{"begin":1185,"end":1191},"obj":"Glycan"}],"attributes":[{"id":"A1","pred":"glycosmos_id","subj":"T1","obj":"https://glycosmos.org/glycans/show/G39738WL"},{"id":"A4","pred":"image","subj":"T1","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G39738WL"},{"id":"A2","pred":"glycosmos_id","subj":"T2","obj":"https://glycosmos.org/glycans/show/G39738WL"},{"id":"A5","pred":"image","subj":"T2","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G39738WL"},{"id":"A3","pred":"glycosmos_id","subj":"T3","obj":"https://glycosmos.org/glycans/show/G39738WL"},{"id":"A6","pred":"image","subj":"T3","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G39738WL"}],"text":"Sequential glycosylations at the multibasic cleavage site of SARS-CoV-2 spike protein regulate viral activity.\nThe multibasic furin cleavage site at the S1/S2 boundary of the spike protein is a hallmark of SARS-CoV-2 and plays a crucial role in viral infection. However, the mechanism underlying furin activation and its regulation remain poorly understood. Here, we show that GalNAc-T3 and T7 jointly initiate clustered O-glycosylations in the furin cleavage site of the SARS-CoV-2 spike protein, which inhibit furin processing, suppress the incorporation of the spike protein into virus-like-particles and affect viral infection. Mechanistic analysis reveals that the assembly of the spike protein into virus-like particles relies on interactions between the furin-cleaved spike protein and the membrane protein of SARS-CoV-2, suggesting a possible mechanism for furin activation. Interestingly, mutations in the spike protein of the alpha and delta variants of the virus confer resistance against glycosylation by GalNAc-T3 and T7. In the omicron variant, additional mutations reverse this resistance, making the spike protein susceptible to glycosylation in vitro and sensitive to GalNAc-T3 and T7 expression in human lung cells. Our findings highlight the role of glycosylation as a defense mechanism employed by host cells against SARS-CoV-2 and shed light on the evolutionary interplay between the host and the virus."}

{"project":"GlyCosmos15-CL","denotations":[{"id":"T1","span":{"begin":946,"end":951},"obj":"Cell"}],"attributes":[{"id":"A1","pred":"cl_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL:0004124"}],"text":"Sequential glycosylations at the multibasic cleavage site of SARS-CoV-2 spike protein regulate viral activity.\nThe multibasic furin cleavage site at the S1/S2 boundary of the spike protein is a hallmark of SARS-CoV-2 and plays a crucial role in viral infection. However, the mechanism underlying furin activation and its regulation remain poorly understood. Here, we show that GalNAc-T3 and T7 jointly initiate clustered O-glycosylations in the furin cleavage site of the SARS-CoV-2 spike protein, which inhibit furin processing, suppress the incorporation of the spike protein into virus-like-particles and affect viral infection. Mechanistic analysis reveals that the assembly of the spike protein into virus-like particles relies on interactions between the furin-cleaved spike protein and the membrane protein of SARS-CoV-2, suggesting a possible mechanism for furin activation. Interestingly, mutations in the spike protein of the alpha and delta variants of the virus confer resistance against glycosylation by GalNAc-T3 and T7. In the omicron variant, additional mutations reverse this resistance, making the spike protein susceptible to glycosylation in vitro and sensitive to GalNAc-T3 and T7 expression in human lung cells. Our findings highlight the role of glycosylation as a defense mechanism employed by host cells against SARS-CoV-2 and shed light on the evolutionary interplay between the host and the virus."}

{"project":"GlyCosmos15-UBERON","denotations":[{"id":"T1","span":{"begin":797,"end":805},"obj":"Body_part"},{"id":"T2","span":{"begin":1222,"end":1226},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/UBERON_0000094"},{"id":"A2","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/UBERON_0002048"}],"text":"Sequential glycosylations at the multibasic cleavage site of SARS-CoV-2 spike protein regulate viral activity.\nThe multibasic furin cleavage site at the S1/S2 boundary of the spike protein is a hallmark of SARS-CoV-2 and plays a crucial role in viral infection. However, the mechanism underlying furin activation and its regulation remain poorly understood. Here, we show that GalNAc-T3 and T7 jointly initiate clustered O-glycosylations in the furin cleavage site of the SARS-CoV-2 spike protein, which inhibit furin processing, suppress the incorporation of the spike protein into virus-like-particles and affect viral infection. Mechanistic analysis reveals that the assembly of the spike protein into virus-like particles relies on interactions between the furin-cleaved spike protein and the membrane protein of SARS-CoV-2, suggesting a possible mechanism for furin activation. Interestingly, mutations in the spike protein of the alpha and delta variants of the virus confer resistance against glycosylation by GalNAc-T3 and T7. In the omicron variant, additional mutations reverse this resistance, making the spike protein susceptible to glycosylation in vitro and sensitive to GalNAc-T3 and T7 expression in human lung cells. Our findings highlight the role of glycosylation as a defense mechanism employed by host cells against SARS-CoV-2 and shed light on the evolutionary interplay between the host and the virus."}

{"project":"GlyCosmos15-MONDO","denotations":[{"id":"T1","span":{"begin":61,"end":71},"obj":"Disease"},{"id":"T2","span":{"begin":206,"end":216},"obj":"Disease"},{"id":"T3","span":{"begin":245,"end":260},"obj":"Disease"},{"id":"T4","span":{"begin":472,"end":482},"obj":"Disease"},{"id":"T5","span":{"begin":615,"end":630},"obj":"Disease"},{"id":"T6","span":{"begin":817,"end":827},"obj":"Disease"},{"id":"T7","span":{"begin":1337,"end":1347},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"MONDO:0100096"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"MONDO:0100096"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"MONDO:0005108"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"MONDO:0100096"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"MONDO:0005108"},{"id":"A6","pred":"mondo_id","subj":"T6","obj":"MONDO:0100096"},{"id":"A7","pred":"mondo_id","subj":"T7","obj":"MONDO:0100096"}],"namespaces":[{"prefix":"MONDO","uri":"http://purl.obolibrary.org/obo/MONDO_"}],"text":"Sequential glycosylations at the multibasic cleavage site of SARS-CoV-2 spike protein regulate viral activity.\nThe multibasic furin cleavage site at the S1/S2 boundary of the spike protein is a hallmark of SARS-CoV-2 and plays a crucial role in viral infection. However, the mechanism underlying furin activation and its regulation remain poorly understood. Here, we show that GalNAc-T3 and T7 jointly initiate clustered O-glycosylations in the furin cleavage site of the SARS-CoV-2 spike protein, which inhibit furin processing, suppress the incorporation of the spike protein into virus-like-particles and affect viral infection. Mechanistic analysis reveals that the assembly of the spike protein into virus-like particles relies on interactions between the furin-cleaved spike protein and the membrane protein of SARS-CoV-2, suggesting a possible mechanism for furin activation. Interestingly, mutations in the spike protein of the alpha and delta variants of the virus confer resistance against glycosylation by GalNAc-T3 and T7. In the omicron variant, additional mutations reverse this resistance, making the spike protein susceptible to glycosylation in vitro and sensitive to GalNAc-T3 and T7 expression in human lung cells. Our findings highlight the role of glycosylation as a defense mechanism employed by host cells against SARS-CoV-2 and shed light on the evolutionary interplay between the host and the virus."}

{"project":"GlyCosmos15-Taxon","denotations":[{"id":"T1","span":{"begin":61,"end":69},"obj":"Organism"},{"id":"T2","span":{"begin":206,"end":214},"obj":"Organism"},{"id":"T3","span":{"begin":472,"end":480},"obj":"Organism"},{"id":"T4","span":{"begin":817,"end":825},"obj":"Organism"},{"id":"T5","span":{"begin":1042,"end":1049},"obj":"Organism"},{"id":"T6","span":{"begin":1216,"end":1221},"obj":"Organism"},{"id":"T7","span":{"begin":1337,"end":1345},"obj":"Organism"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"694009"},{"id":"A2","pred":"db_id","subj":"T2","obj":"694009"},{"id":"A3","pred":"db_id","subj":"T3","obj":"694009"},{"id":"A4","pred":"db_id","subj":"T4","obj":"694009"},{"id":"A5","pred":"db_id","subj":"T5","obj":"2613138"},{"id":"A6","pred":"db_id","subj":"T6","obj":"9606"},{"id":"A7","pred":"db_id","subj":"T7","obj":"694009"}],"text":"Sequential glycosylations at the multibasic cleavage site of SARS-CoV-2 spike protein regulate viral activity.\nThe multibasic furin cleavage site at the S1/S2 boundary of the spike protein is a hallmark of SARS-CoV-2 and plays a crucial role in viral infection. However, the mechanism underlying furin activation and its regulation remain poorly understood. Here, we show that GalNAc-T3 and T7 jointly initiate clustered O-glycosylations in the furin cleavage site of the SARS-CoV-2 spike protein, which inhibit furin processing, suppress the incorporation of the spike protein into virus-like-particles and affect viral infection. Mechanistic analysis reveals that the assembly of the spike protein into virus-like particles relies on interactions between the furin-cleaved spike protein and the membrane protein of SARS-CoV-2, suggesting a possible mechanism for furin activation. Interestingly, mutations in the spike protein of the alpha and delta variants of the virus confer resistance against glycosylation by GalNAc-T3 and T7. In the omicron variant, additional mutations reverse this resistance, making the spike protein susceptible to glycosylation in vitro and sensitive to GalNAc-T3 and T7 expression in human lung cells. Our findings highlight the role of glycosylation as a defense mechanism employed by host cells against SARS-CoV-2 and shed light on the evolutionary interplay between the host and the virus."}

{"project":"GlyCosmos15-Sentences","blocks":[{"id":"T1","span":{"begin":0,"end":110},"obj":"Sentence"},{"id":"T2","span":{"begin":111,"end":261},"obj":"Sentence"},{"id":"T3","span":{"begin":262,"end":357},"obj":"Sentence"},{"id":"T4","span":{"begin":358,"end":631},"obj":"Sentence"},{"id":"T5","span":{"begin":632,"end":882},"obj":"Sentence"},{"id":"T6","span":{"begin":883,"end":1034},"obj":"Sentence"},{"id":"T7","span":{"begin":1035,"end":1233},"obj":"Sentence"},{"id":"T8","span":{"begin":1234,"end":1424},"obj":"Sentence"}],"text":"Sequential glycosylations at the multibasic cleavage site of SARS-CoV-2 spike protein regulate viral activity.\nThe multibasic furin cleavage site at the S1/S2 boundary of the spike protein is a hallmark of SARS-CoV-2 and plays a crucial role in viral infection. However, the mechanism underlying furin activation and its regulation remain poorly understood. Here, we show that GalNAc-T3 and T7 jointly initiate clustered O-glycosylations in the furin cleavage site of the SARS-CoV-2 spike protein, which inhibit furin processing, suppress the incorporation of the spike protein into virus-like-particles and affect viral infection. Mechanistic analysis reveals that the assembly of the spike protein into virus-like particles relies on interactions between the furin-cleaved spike protein and the membrane protein of SARS-CoV-2, suggesting a possible mechanism for furin activation. Interestingly, mutations in the spike protein of the alpha and delta variants of the virus confer resistance against glycosylation by GalNAc-T3 and T7. In the omicron variant, additional mutations reverse this resistance, making the spike protein susceptible to glycosylation in vitro and sensitive to GalNAc-T3 and T7 expression in human lung cells. Our findings highlight the role of glycosylation as a defense mechanism employed by host cells against SARS-CoV-2 and shed light on the evolutionary interplay between the host and the virus."}

{"project":"GlyCosmos15-FMA","denotations":[{"id":"T1","span":{"begin":1222,"end":1226},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"FMA:7195"}],"namespaces":[{"prefix":"FMA","uri":"http://purl.org/sig/ont/fma/fma"}],"text":"Sequential glycosylations at the multibasic cleavage site of SARS-CoV-2 spike protein regulate viral activity.\nThe multibasic furin cleavage site at the S1/S2 boundary of the spike protein is a hallmark of SARS-CoV-2 and plays a crucial role in viral infection. However, the mechanism underlying furin activation and its regulation remain poorly understood. Here, we show that GalNAc-T3 and T7 jointly initiate clustered O-glycosylations in the furin cleavage site of the SARS-CoV-2 spike protein, which inhibit furin processing, suppress the incorporation of the spike protein into virus-like-particles and affect viral infection. Mechanistic analysis reveals that the assembly of the spike protein into virus-like particles relies on interactions between the furin-cleaved spike protein and the membrane protein of SARS-CoV-2, suggesting a possible mechanism for furin activation. Interestingly, mutations in the spike protein of the alpha and delta variants of the virus confer resistance against glycosylation by GalNAc-T3 and T7. In the omicron variant, additional mutations reverse this resistance, making the spike protein susceptible to glycosylation in vitro and sensitive to GalNAc-T3 and T7 expression in human lung cells. Our findings highlight the role of glycosylation as a defense mechanism employed by host cells against SARS-CoV-2 and shed light on the evolutionary interplay between the host and the virus."}

{"project":"GlyCosmos15-MAT","denotations":[{"id":"T1","span":{"begin":1222,"end":1226},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"mat_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MAT_0000135"}],"text":"Sequential glycosylations at the multibasic cleavage site of SARS-CoV-2 spike protein regulate viral activity.\nThe multibasic furin cleavage site at the S1/S2 boundary of the spike protein is a hallmark of SARS-CoV-2 and plays a crucial role in viral infection. However, the mechanism underlying furin activation and its regulation remain poorly understood. Here, we show that GalNAc-T3 and T7 jointly initiate clustered O-glycosylations in the furin cleavage site of the SARS-CoV-2 spike protein, which inhibit furin processing, suppress the incorporation of the spike protein into virus-like-particles and affect viral infection. Mechanistic analysis reveals that the assembly of the spike protein into virus-like particles relies on interactions between the furin-cleaved spike protein and the membrane protein of SARS-CoV-2, suggesting a possible mechanism for furin activation. Interestingly, mutations in the spike protein of the alpha and delta variants of the virus confer resistance against glycosylation by GalNAc-T3 and T7. In the omicron variant, additional mutations reverse this resistance, making the spike protein susceptible to glycosylation in vitro and sensitive to GalNAc-T3 and T7 expression in human lung cells. Our findings highlight the role of glycosylation as a defense mechanism employed by host cells against SARS-CoV-2 and shed light on the evolutionary interplay between the host and the virus."}

{"project":"NCBITAXON","denotations":[{"id":"T1","span":{"begin":61,"end":69},"obj":"OrganismTaxon"},{"id":"T2","span":{"begin":206,"end":214},"obj":"OrganismTaxon"},{"id":"T3","span":{"begin":472,"end":480},"obj":"OrganismTaxon"},{"id":"T4","span":{"begin":817,"end":825},"obj":"OrganismTaxon"},{"id":"T5","span":{"begin":1042,"end":1049},"obj":"OrganismTaxon"},{"id":"T6","span":{"begin":1216,"end":1221},"obj":"OrganismTaxon"},{"id":"T7","span":{"begin":1337,"end":1345},"obj":"OrganismTaxon"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"694009"},{"id":"A2","pred":"db_id","subj":"T2","obj":"694009"},{"id":"A3","pred":"db_id","subj":"T3","obj":"694009"},{"id":"A4","pred":"db_id","subj":"T4","obj":"694009"},{"id":"A5","pred":"db_id","subj":"T5","obj":"2613138"},{"id":"A6","pred":"db_id","subj":"T6","obj":"9606"},{"id":"A7","pred":"db_id","subj":"T7","obj":"694009"}],"text":"Sequential glycosylations at the multibasic cleavage site of SARS-CoV-2 spike protein regulate viral activity.\nThe multibasic furin cleavage site at the S1/S2 boundary of the spike protein is a hallmark of SARS-CoV-2 and plays a crucial role in viral infection. However, the mechanism underlying furin activation and its regulation remain poorly understood. Here, we show that GalNAc-T3 and T7 jointly initiate clustered O-glycosylations in the furin cleavage site of the SARS-CoV-2 spike protein, which inhibit furin processing, suppress the incorporation of the spike protein into virus-like-particles and affect viral infection. Mechanistic analysis reveals that the assembly of the spike protein into virus-like particles relies on interactions between the furin-cleaved spike protein and the membrane protein of SARS-CoV-2, suggesting a possible mechanism for furin activation. Interestingly, mutations in the spike protein of the alpha and delta variants of the virus confer resistance against glycosylation by GalNAc-T3 and T7. In the omicron variant, additional mutations reverse this resistance, making the spike protein susceptible to glycosylation in vitro and sensitive to GalNAc-T3 and T7 expression in human lung cells. Our findings highlight the role of glycosylation as a defense mechanism employed by host cells against SARS-CoV-2 and shed light on the evolutionary interplay between the host and the virus."}

{"project":"Anatomy-UBERON","denotations":[{"id":"T1","span":{"begin":797,"end":805},"obj":"Body_part"},{"id":"T4","span":{"begin":1222,"end":1226},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/GO_0016020"},{"id":"A2","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/UBERON_0000094"},{"id":"A3","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/UBERON_0000158"},{"id":"A4","pred":"uberon_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/UBERON_0002048"}],"text":"Sequential glycosylations at the multibasic cleavage site of SARS-CoV-2 spike protein regulate viral activity.\nThe multibasic furin cleavage site at the S1/S2 boundary of the spike protein is a hallmark of SARS-CoV-2 and plays a crucial role in viral infection. However, the mechanism underlying furin activation and its regulation remain poorly understood. Here, we show that GalNAc-T3 and T7 jointly initiate clustered O-glycosylations in the furin cleavage site of the SARS-CoV-2 spike protein, which inhibit furin processing, suppress the incorporation of the spike protein into virus-like-particles and affect viral infection. Mechanistic analysis reveals that the assembly of the spike protein into virus-like particles relies on interactions between the furin-cleaved spike protein and the membrane protein of SARS-CoV-2, suggesting a possible mechanism for furin activation. Interestingly, mutations in the spike protein of the alpha and delta variants of the virus confer resistance against glycosylation by GalNAc-T3 and T7. In the omicron variant, additional mutations reverse this resistance, making the spike protein susceptible to glycosylation in vitro and sensitive to GalNAc-T3 and T7 expression in human lung cells. Our findings highlight the role of glycosylation as a defense mechanism employed by host cells against SARS-CoV-2 and shed light on the evolutionary interplay between the host and the virus."}

{"project":"Anatomy-MAT","denotations":[{"id":"T1","span":{"begin":1222,"end":1226},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"mat_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MAT_0000135"}],"text":"Sequential glycosylations at the multibasic cleavage site of SARS-CoV-2 spike protein regulate viral activity.\nThe multibasic furin cleavage site at the S1/S2 boundary of the spike protein is a hallmark of SARS-CoV-2 and plays a crucial role in viral infection. However, the mechanism underlying furin activation and its regulation remain poorly understood. Here, we show that GalNAc-T3 and T7 jointly initiate clustered O-glycosylations in the furin cleavage site of the SARS-CoV-2 spike protein, which inhibit furin processing, suppress the incorporation of the spike protein into virus-like-particles and affect viral infection. Mechanistic analysis reveals that the assembly of the spike protein into virus-like particles relies on interactions between the furin-cleaved spike protein and the membrane protein of SARS-CoV-2, suggesting a possible mechanism for furin activation. Interestingly, mutations in the spike protein of the alpha and delta variants of the virus confer resistance against glycosylation by GalNAc-T3 and T7. In the omicron variant, additional mutations reverse this resistance, making the spike protein susceptible to glycosylation in vitro and sensitive to GalNAc-T3 and T7 expression in human lung cells. Our findings highlight the role of glycosylation as a defense mechanism employed by host cells against SARS-CoV-2 and shed light on the evolutionary interplay between the host and the virus."}

{"project":"CL-cell","denotations":[{"id":"T1","span":{"begin":946,"end":951},"obj":"Cell"}],"attributes":[{"id":"A1","pred":"cl_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL:0004124"}],"text":"Sequential glycosylations at the multibasic cleavage site of SARS-CoV-2 spike protein regulate viral activity.\nThe multibasic furin cleavage site at the S1/S2 boundary of the spike protein is a hallmark of SARS-CoV-2 and plays a crucial role in viral infection. However, the mechanism underlying furin activation and its regulation remain poorly understood. Here, we show that GalNAc-T3 and T7 jointly initiate clustered O-glycosylations in the furin cleavage site of the SARS-CoV-2 spike protein, which inhibit furin processing, suppress the incorporation of the spike protein into virus-like-particles and affect viral infection. Mechanistic analysis reveals that the assembly of the spike protein into virus-like particles relies on interactions between the furin-cleaved spike protein and the membrane protein of SARS-CoV-2, suggesting a possible mechanism for furin activation. Interestingly, mutations in the spike protein of the alpha and delta variants of the virus confer resistance against glycosylation by GalNAc-T3 and T7. In the omicron variant, additional mutations reverse this resistance, making the spike protein susceptible to glycosylation in vitro and sensitive to GalNAc-T3 and T7 expression in human lung cells. Our findings highlight the role of glycosylation as a defense mechanism employed by host cells against SARS-CoV-2 and shed light on the evolutionary interplay between the host and the virus."}