PMC:7321036 / 51269-53075 JSONTXT

{"project":"LitCovid-PMC-OGER-BB","denotations":[{"id":"T171","span":{"begin":1030,"end":1051},"obj":"SP_7"},{"id":"T172","span":{"begin":1746,"end":1779},"obj":"GO:0065007"}],"text":"The most strongly regulated kinases fall into a set of signaling pathways that include p38/MAPK signaling, AKT and ERK signaling, Rho GTPase and CK2 cytoskeleton signaling, and cell cycle regulation. The downregulation of ROCK and PAK kinase activity and upregulation of CK2 cytoskeleton-related targets suggest virus-induced changes in cytoskeleton organization. Imaging of infected cells revealed formation of actin-rich filopodia containing viral proteins. Higher-resolution electron microscopy data confirm the presence of assembled viral particles in these structures. Many viruses, including vaccinia, Ebola, and Marburg, hijack the host cell cytoskeleton to promote egress and rapid cell-to-cell spread across epithelial monolayers. Vaccinia promotes Arp2/3-dependent actin assembly, producing a filopodial protrusion with a virus at the tip (Leite and Way 2015). In contrast, Marburg virus hijacks the unconventional motor protein Myosin X, which promotes filopodium formation and trafficks the virus along the filopodium shaft. The SARS-CoV-2 protein clusters peppered throughout the length of filopodial protrusions more closely resemble Marburg than vaccinia, but additional work is required to understand whether SARS-CoV-2 makes use of either Myosin X motor activity or actin filament assembly to move along filopodia. CK2 is known to phosphorylate myosin proteins at endocytic sites to drive actin polymerization (Fernández-Golbano et al., 2014). Furthermore, CK2 has been found to regulate actin tail formation during vaccinia virus infection, enabling efficient cell-to-cell spread of the virus (Alvarez and Agaisse 2012; Smith and Law 2004). Here the CK2 inhibitor silmitasertib displayed robust antiviral activity, suggesting a role of this kinase in regulating the SARS-CoV-2 life cycle."}

{"project":"LitCovid-PD-FMA-UBERON","denotations":[{"id":"T398","span":{"begin":149,"end":161},"obj":"Body_part"},{"id":"T399","span":{"begin":177,"end":181},"obj":"Body_part"},{"id":"T400","span":{"begin":275,"end":287},"obj":"Body_part"},{"id":"T401","span":{"begin":337,"end":349},"obj":"Body_part"},{"id":"T402","span":{"begin":384,"end":389},"obj":"Body_part"},{"id":"T403","span":{"begin":412,"end":417},"obj":"Body_part"},{"id":"T404","span":{"begin":450,"end":458},"obj":"Body_part"},{"id":"T405","span":{"begin":644,"end":648},"obj":"Body_part"},{"id":"T406","span":{"begin":649,"end":661},"obj":"Body_part"},{"id":"T407","span":{"begin":690,"end":694},"obj":"Body_part"},{"id":"T408","span":{"begin":698,"end":702},"obj":"Body_part"},{"id":"T409","span":{"begin":775,"end":780},"obj":"Body_part"},{"id":"T410","span":{"begin":925,"end":938},"obj":"Body_part"},{"id":"T411","span":{"begin":939,"end":945},"obj":"Body_part"},{"id":"T412","span":{"begin":1052,"end":1059},"obj":"Body_part"},{"id":"T413","span":{"begin":1256,"end":1262},"obj":"Body_part"},{"id":"T414","span":{"begin":1283,"end":1297},"obj":"Body_part"},{"id":"T415","span":{"begin":1362,"end":1368},"obj":"Body_part"},{"id":"T416","span":{"begin":1369,"end":1377},"obj":"Body_part"},{"id":"T417","span":{"begin":1406,"end":1411},"obj":"Body_part"},{"id":"T418","span":{"begin":1505,"end":1510},"obj":"Body_part"},{"id":"T419","span":{"begin":1578,"end":1582},"obj":"Body_part"},{"id":"T420","span":{"begin":1586,"end":1590},"obj":"Body_part"}],"attributes":[{"id":"A398","pred":"fma_id","subj":"T398","obj":"http://purl.org/sig/ont/fma/fma63834"},{"id":"A399","pred":"fma_id","subj":"T399","obj":"http://purl.org/sig/ont/fma/fma68646"},{"id":"A400","pred":"fma_id","subj":"T400","obj":"http://purl.org/sig/ont/fma/fma63834"},{"id":"A401","pred":"fma_id","subj":"T401","obj":"http://purl.org/sig/ont/fma/fma63834"},{"id":"A402","pred":"fma_id","subj":"T402","obj":"http://purl.org/sig/ont/fma/fma68646"},{"id":"A403","pred":"fma_id","subj":"T403","obj":"http://purl.org/sig/ont/fma/fma67843"},{"id":"A404","pred":"fma_id","subj":"T404","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A405","pred":"fma_id","subj":"T405","obj":"http://purl.org/sig/ont/fma/fma68646"},{"id":"A406","pred":"fma_id","subj":"T406","obj":"http://purl.org/sig/ont/fma/fma63834"},{"id":"A407","pred":"fma_id","subj":"T407","obj":"http://purl.org/sig/ont/fma/fma68646"},{"id":"A408","pred":"fma_id","subj":"T408","obj":"http://purl.org/sig/ont/fma/fma68646"},{"id":"A409","pred":"fma_id","subj":"T409","obj":"http://purl.org/sig/ont/fma/fma67843"},{"id":"A410","pred":"fma_id","subj":"T410","obj":"http://purl.org/sig/ont/fma/fma62290"},{"id":"A411","pred":"fma_id","subj":"T411","obj":"http://purl.org/sig/ont/fma/fma67840"},{"id":"A412","pred":"fma_id","subj":"T412","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A413","pred":"fma_id","subj":"T413","obj":"http://purl.org/sig/ont/fma/fma67840"},{"id":"A414","pred":"fma_id","subj":"T414","obj":"http://purl.org/sig/ont/fma/fma63850"},{"id":"A415","pred":"fma_id","subj":"T415","obj":"http://purl.org/sig/ont/fma/fma67840"},{"id":"A416","pred":"fma_id","subj":"T416","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A417","pred":"fma_id","subj":"T417","obj":"http://purl.org/sig/ont/fma/fma67843"},{"id":"A418","pred":"fma_id","subj":"T418","obj":"http://purl.org/sig/ont/fma/fma67843"},{"id":"A419","pred":"fma_id","subj":"T419","obj":"http://purl.org/sig/ont/fma/fma68646"},{"id":"A420","pred":"fma_id","subj":"T420","obj":"http://purl.org/sig/ont/fma/fma68646"}],"text":"The most strongly regulated kinases fall into a set of signaling pathways that include p38/MAPK signaling, AKT and ERK signaling, Rho GTPase and CK2 cytoskeleton signaling, and cell cycle regulation. The downregulation of ROCK and PAK kinase activity and upregulation of CK2 cytoskeleton-related targets suggest virus-induced changes in cytoskeleton organization. Imaging of infected cells revealed formation of actin-rich filopodia containing viral proteins. Higher-resolution electron microscopy data confirm the presence of assembled viral particles in these structures. Many viruses, including vaccinia, Ebola, and Marburg, hijack the host cell cytoskeleton to promote egress and rapid cell-to-cell spread across epithelial monolayers. Vaccinia promotes Arp2/3-dependent actin assembly, producing a filopodial protrusion with a virus at the tip (Leite and Way 2015). In contrast, Marburg virus hijacks the unconventional motor protein Myosin X, which promotes filopodium formation and trafficks the virus along the filopodium shaft. The SARS-CoV-2 protein clusters peppered throughout the length of filopodial protrusions more closely resemble Marburg than vaccinia, but additional work is required to understand whether SARS-CoV-2 makes use of either Myosin X motor activity or actin filament assembly to move along filopodia. CK2 is known to phosphorylate myosin proteins at endocytic sites to drive actin polymerization (Fernández-Golbano et al., 2014). Furthermore, CK2 has been found to regulate actin tail formation during vaccinia virus infection, enabling efficient cell-to-cell spread of the virus (Alvarez and Agaisse 2012; Smith and Law 2004). Here the CK2 inhibitor silmitasertib displayed robust antiviral activity, suggesting a role of this kinase in regulating the SARS-CoV-2 life cycle."}

{"project":"LitCovid-PD-UBERON","denotations":[{"id":"T17","span":{"begin":845,"end":848},"obj":"Body_part"},{"id":"T18","span":{"begin":1511,"end":1515},"obj":"Body_part"}],"attributes":[{"id":"A17","pred":"uberon_id","subj":"T17","obj":"http://purl.obolibrary.org/obo/UBERON_2001840"},{"id":"A18","pred":"uberon_id","subj":"T18","obj":"http://purl.obolibrary.org/obo/UBERON_0002415"}],"text":"The most strongly regulated kinases fall into a set of signaling pathways that include p38/MAPK signaling, AKT and ERK signaling, Rho GTPase and CK2 cytoskeleton signaling, and cell cycle regulation. The downregulation of ROCK and PAK kinase activity and upregulation of CK2 cytoskeleton-related targets suggest virus-induced changes in cytoskeleton organization. Imaging of infected cells revealed formation of actin-rich filopodia containing viral proteins. Higher-resolution electron microscopy data confirm the presence of assembled viral particles in these structures. Many viruses, including vaccinia, Ebola, and Marburg, hijack the host cell cytoskeleton to promote egress and rapid cell-to-cell spread across epithelial monolayers. Vaccinia promotes Arp2/3-dependent actin assembly, producing a filopodial protrusion with a virus at the tip (Leite and Way 2015). In contrast, Marburg virus hijacks the unconventional motor protein Myosin X, which promotes filopodium formation and trafficks the virus along the filopodium shaft. The SARS-CoV-2 protein clusters peppered throughout the length of filopodial protrusions more closely resemble Marburg than vaccinia, but additional work is required to understand whether SARS-CoV-2 makes use of either Myosin X motor activity or actin filament assembly to move along filopodia. CK2 is known to phosphorylate myosin proteins at endocytic sites to drive actin polymerization (Fernández-Golbano et al., 2014). Furthermore, CK2 has been found to regulate actin tail formation during vaccinia virus infection, enabling efficient cell-to-cell spread of the virus (Alvarez and Agaisse 2012; Smith and Law 2004). Here the CK2 inhibitor silmitasertib displayed robust antiviral activity, suggesting a role of this kinase in regulating the SARS-CoV-2 life cycle."}

{"project":"LitCovid-PD-MONDO","denotations":[{"id":"T258","span":{"begin":598,"end":606},"obj":"Disease"},{"id":"T259","span":{"begin":608,"end":613},"obj":"Disease"},{"id":"T260","span":{"begin":740,"end":748},"obj":"Disease"},{"id":"T261","span":{"begin":1041,"end":1049},"obj":"Disease"},{"id":"T262","span":{"begin":1161,"end":1169},"obj":"Disease"},{"id":"T263","span":{"begin":1225,"end":1233},"obj":"Disease"},{"id":"T264","span":{"begin":1533,"end":1541},"obj":"Disease"},{"id":"T265","span":{"begin":1542,"end":1557},"obj":"Disease"},{"id":"T266","span":{"begin":1548,"end":1557},"obj":"Disease"},{"id":"T267","span":{"begin":1784,"end":1792},"obj":"Disease"}],"attributes":[{"id":"A258","pred":"mondo_id","subj":"T258","obj":"http://purl.obolibrary.org/obo/MONDO_0002595"},{"id":"A259","pred":"mondo_id","subj":"T259","obj":"http://purl.obolibrary.org/obo/MONDO_0005737"},{"id":"A260","pred":"mondo_id","subj":"T260","obj":"http://purl.obolibrary.org/obo/MONDO_0002595"},{"id":"A261","pred":"mondo_id","subj":"T261","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A262","pred":"mondo_id","subj":"T262","obj":"http://purl.obolibrary.org/obo/MONDO_0002595"},{"id":"A263","pred":"mondo_id","subj":"T263","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A264","pred":"mondo_id","subj":"T264","obj":"http://purl.obolibrary.org/obo/MONDO_0002595"},{"id":"A265","pred":"mondo_id","subj":"T265","obj":"http://purl.obolibrary.org/obo/MONDO_0005108"},{"id":"A266","pred":"mondo_id","subj":"T266","obj":"http://purl.obolibrary.org/obo/MONDO_0005550"},{"id":"A267","pred":"mondo_id","subj":"T267","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"}],"text":"The most strongly regulated kinases fall into a set of signaling pathways that include p38/MAPK signaling, AKT and ERK signaling, Rho GTPase and CK2 cytoskeleton signaling, and cell cycle regulation. The downregulation of ROCK and PAK kinase activity and upregulation of CK2 cytoskeleton-related targets suggest virus-induced changes in cytoskeleton organization. Imaging of infected cells revealed formation of actin-rich filopodia containing viral proteins. Higher-resolution electron microscopy data confirm the presence of assembled viral particles in these structures. Many viruses, including vaccinia, Ebola, and Marburg, hijack the host cell cytoskeleton to promote egress and rapid cell-to-cell spread across epithelial monolayers. Vaccinia promotes Arp2/3-dependent actin assembly, producing a filopodial protrusion with a virus at the tip (Leite and Way 2015). In contrast, Marburg virus hijacks the unconventional motor protein Myosin X, which promotes filopodium formation and trafficks the virus along the filopodium shaft. The SARS-CoV-2 protein clusters peppered throughout the length of filopodial protrusions more closely resemble Marburg than vaccinia, but additional work is required to understand whether SARS-CoV-2 makes use of either Myosin X motor activity or actin filament assembly to move along filopodia. CK2 is known to phosphorylate myosin proteins at endocytic sites to drive actin polymerization (Fernández-Golbano et al., 2014). Furthermore, CK2 has been found to regulate actin tail formation during vaccinia virus infection, enabling efficient cell-to-cell spread of the virus (Alvarez and Agaisse 2012; Smith and Law 2004). Here the CK2 inhibitor silmitasertib displayed robust antiviral activity, suggesting a role of this kinase in regulating the SARS-CoV-2 life cycle."}

{"project":"LitCovid-PD-CLO","denotations":[{"id":"T680","span":{"begin":46,"end":47},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T681","span":{"begin":55,"end":64},"obj":"http://purl.obolibrary.org/obo/SO_0000418"},{"id":"T682","span":{"begin":96,"end":105},"obj":"http://purl.obolibrary.org/obo/SO_0000418"},{"id":"T683","span":{"begin":119,"end":128},"obj":"http://purl.obolibrary.org/obo/SO_0000418"},{"id":"T684","span":{"begin":130,"end":133},"obj":"http://purl.obolibrary.org/obo/CLO_0051142"},{"id":"T685","span":{"begin":162,"end":171},"obj":"http://purl.obolibrary.org/obo/SO_0000418"},{"id":"T686","span":{"begin":177,"end":181},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T687","span":{"begin":242,"end":250},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T688","span":{"begin":312,"end":317},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_10239"},{"id":"T689","span":{"begin":350,"end":362},"obj":"http://purl.obolibrary.org/obo/OBI_0000245"},{"id":"T690","span":{"begin":384,"end":389},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T691","span":{"begin":579,"end":586},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_10239"},{"id":"T692","span":{"begin":644,"end":648},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T693","span":{"begin":690,"end":694},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T694","span":{"begin":698,"end":702},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T695","span":{"begin":717,"end":727},"obj":"http://purl.obolibrary.org/obo/CL_0000066"},{"id":"T696","span":{"begin":801,"end":802},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T697","span":{"begin":830,"end":831},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T698","span":{"begin":832,"end":837},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_10239"},{"id":"T699","span":{"begin":892,"end":897},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_10239"},{"id":"T700","span":{"begin":1003,"end":1008},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_10239"},{"id":"T701","span":{"begin":1271,"end":1279},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T702","span":{"begin":1478,"end":1481},"obj":"http://purl.obolibrary.org/obo/CLO_0051582"},{"id":"T703","span":{"begin":1511,"end":1515},"obj":"http://purl.obolibrary.org/obo/UBERON_0002415"},{"id":"T704","span":{"begin":1542,"end":1547},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_10239"},{"id":"T705","span":{"begin":1578,"end":1582},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T706","span":{"begin":1586,"end":1590},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T707","span":{"begin":1605,"end":1610},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_10239"},{"id":"T708","span":{"begin":1723,"end":1731},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T709","span":{"begin":1744,"end":1745},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"}],"text":"The most strongly regulated kinases fall into a set of signaling pathways that include p38/MAPK signaling, AKT and ERK signaling, Rho GTPase and CK2 cytoskeleton signaling, and cell cycle regulation. The downregulation of ROCK and PAK kinase activity and upregulation of CK2 cytoskeleton-related targets suggest virus-induced changes in cytoskeleton organization. Imaging of infected cells revealed formation of actin-rich filopodia containing viral proteins. Higher-resolution electron microscopy data confirm the presence of assembled viral particles in these structures. Many viruses, including vaccinia, Ebola, and Marburg, hijack the host cell cytoskeleton to promote egress and rapid cell-to-cell spread across epithelial monolayers. Vaccinia promotes Arp2/3-dependent actin assembly, producing a filopodial protrusion with a virus at the tip (Leite and Way 2015). In contrast, Marburg virus hijacks the unconventional motor protein Myosin X, which promotes filopodium formation and trafficks the virus along the filopodium shaft. The SARS-CoV-2 protein clusters peppered throughout the length of filopodial protrusions more closely resemble Marburg than vaccinia, but additional work is required to understand whether SARS-CoV-2 makes use of either Myosin X motor activity or actin filament assembly to move along filopodia. CK2 is known to phosphorylate myosin proteins at endocytic sites to drive actin polymerization (Fernández-Golbano et al., 2014). Furthermore, CK2 has been found to regulate actin tail formation during vaccinia virus infection, enabling efficient cell-to-cell spread of the virus (Alvarez and Agaisse 2012; Smith and Law 2004). Here the CK2 inhibitor silmitasertib displayed robust antiviral activity, suggesting a role of this kinase in regulating the SARS-CoV-2 life cycle."}

{"project":"LitCovid-PD-CHEBI","denotations":[{"id":"T7390","span":{"begin":450,"end":458},"obj":"Chemical"},{"id":"T1761","span":{"begin":478,"end":486},"obj":"Chemical"},{"id":"T23812","span":{"begin":931,"end":938},"obj":"Chemical"},{"id":"T60269","span":{"begin":1052,"end":1059},"obj":"Chemical"},{"id":"T80207","span":{"begin":1369,"end":1377},"obj":"Chemical"},{"id":"T5589","span":{"begin":1672,"end":1681},"obj":"Chemical"},{"id":"T63232","span":{"begin":1713,"end":1722},"obj":"Chemical"}],"attributes":[{"id":"A19761","pred":"chebi_id","subj":"T7390","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"id":"A28047","pred":"chebi_id","subj":"T1761","obj":"http://purl.obolibrary.org/obo/CHEBI_10545"},{"id":"A42027","pred":"chebi_id","subj":"T23812","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"id":"A4776","pred":"chebi_id","subj":"T60269","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"id":"A23440","pred":"chebi_id","subj":"T80207","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"id":"A44751","pred":"chebi_id","subj":"T5589","obj":"http://purl.obolibrary.org/obo/CHEBI_35222"},{"id":"A19372","pred":"chebi_id","subj":"T63232","obj":"http://purl.obolibrary.org/obo/CHEBI_22587"}],"text":"The most strongly regulated kinases fall into a set of signaling pathways that include p38/MAPK signaling, AKT and ERK signaling, Rho GTPase and CK2 cytoskeleton signaling, and cell cycle regulation. The downregulation of ROCK and PAK kinase activity and upregulation of CK2 cytoskeleton-related targets suggest virus-induced changes in cytoskeleton organization. Imaging of infected cells revealed formation of actin-rich filopodia containing viral proteins. Higher-resolution electron microscopy data confirm the presence of assembled viral particles in these structures. Many viruses, including vaccinia, Ebola, and Marburg, hijack the host cell cytoskeleton to promote egress and rapid cell-to-cell spread across epithelial monolayers. Vaccinia promotes Arp2/3-dependent actin assembly, producing a filopodial protrusion with a virus at the tip (Leite and Way 2015). In contrast, Marburg virus hijacks the unconventional motor protein Myosin X, which promotes filopodium formation and trafficks the virus along the filopodium shaft. The SARS-CoV-2 protein clusters peppered throughout the length of filopodial protrusions more closely resemble Marburg than vaccinia, but additional work is required to understand whether SARS-CoV-2 makes use of either Myosin X motor activity or actin filament assembly to move along filopodia. CK2 is known to phosphorylate myosin proteins at endocytic sites to drive actin polymerization (Fernández-Golbano et al., 2014). Furthermore, CK2 has been found to regulate actin tail formation during vaccinia virus infection, enabling efficient cell-to-cell spread of the virus (Alvarez and Agaisse 2012; Smith and Law 2004). Here the CK2 inhibitor silmitasertib displayed robust antiviral activity, suggesting a role of this kinase in regulating the SARS-CoV-2 life cycle."}

{"project":"LitCovid-PD-GO-BP","denotations":[{"id":"T363","span":{"begin":55,"end":73},"obj":"http://purl.obolibrary.org/obo/GO_0007165"},{"id":"T364","span":{"begin":55,"end":64},"obj":"http://purl.obolibrary.org/obo/GO_0023052"},{"id":"T365","span":{"begin":87,"end":105},"obj":"http://purl.obolibrary.org/obo/GO_0051403"},{"id":"T366","span":{"begin":91,"end":105},"obj":"http://purl.obolibrary.org/obo/GO_0000165"},{"id":"T367","span":{"begin":91,"end":95},"obj":"http://purl.obolibrary.org/obo/GO_0004707"},{"id":"T368","span":{"begin":96,"end":105},"obj":"http://purl.obolibrary.org/obo/GO_0023052"},{"id":"T369","span":{"begin":119,"end":128},"obj":"http://purl.obolibrary.org/obo/GO_0023052"},{"id":"T370","span":{"begin":162,"end":171},"obj":"http://purl.obolibrary.org/obo/GO_0023052"},{"id":"T371","span":{"begin":177,"end":198},"obj":"http://purl.obolibrary.org/obo/GO_0051726"},{"id":"T372","span":{"begin":177,"end":187},"obj":"http://purl.obolibrary.org/obo/GO_0007049"},{"id":"T373","span":{"begin":188,"end":198},"obj":"http://purl.obolibrary.org/obo/GO_0065007"},{"id":"T374","span":{"begin":235,"end":250},"obj":"http://purl.obolibrary.org/obo/GO_0016301"},{"id":"T375","span":{"begin":337,"end":362},"obj":"http://purl.obolibrary.org/obo/GO_0007010"},{"id":"T376","span":{"begin":399,"end":408},"obj":"http://purl.obolibrary.org/obo/GO_0009058"},{"id":"T377","span":{"begin":964,"end":984},"obj":"http://purl.obolibrary.org/obo/GO_0046847"},{"id":"T378","span":{"begin":975,"end":984},"obj":"http://purl.obolibrary.org/obo/GO_0009058"},{"id":"T379","span":{"begin":1348,"end":1361},"obj":"http://purl.obolibrary.org/obo/GO_0016310"},{"id":"T380","span":{"begin":1406,"end":1426},"obj":"http://purl.obolibrary.org/obo/GO_0030041"},{"id":"T381","span":{"begin":1516,"end":1525},"obj":"http://purl.obolibrary.org/obo/GO_0009058"}],"text":"The most strongly regulated kinases fall into a set of signaling pathways that include p38/MAPK signaling, AKT and ERK signaling, Rho GTPase and CK2 cytoskeleton signaling, and cell cycle regulation. The downregulation of ROCK and PAK kinase activity and upregulation of CK2 cytoskeleton-related targets suggest virus-induced changes in cytoskeleton organization. Imaging of infected cells revealed formation of actin-rich filopodia containing viral proteins. Higher-resolution electron microscopy data confirm the presence of assembled viral particles in these structures. Many viruses, including vaccinia, Ebola, and Marburg, hijack the host cell cytoskeleton to promote egress and rapid cell-to-cell spread across epithelial monolayers. Vaccinia promotes Arp2/3-dependent actin assembly, producing a filopodial protrusion with a virus at the tip (Leite and Way 2015). In contrast, Marburg virus hijacks the unconventional motor protein Myosin X, which promotes filopodium formation and trafficks the virus along the filopodium shaft. The SARS-CoV-2 protein clusters peppered throughout the length of filopodial protrusions more closely resemble Marburg than vaccinia, but additional work is required to understand whether SARS-CoV-2 makes use of either Myosin X motor activity or actin filament assembly to move along filopodia. CK2 is known to phosphorylate myosin proteins at endocytic sites to drive actin polymerization (Fernández-Golbano et al., 2014). Furthermore, CK2 has been found to regulate actin tail formation during vaccinia virus infection, enabling efficient cell-to-cell spread of the virus (Alvarez and Agaisse 2012; Smith and Law 2004). Here the CK2 inhibitor silmitasertib displayed robust antiviral activity, suggesting a role of this kinase in regulating the SARS-CoV-2 life cycle."}

{"project":"LitCovid-PubTator","denotations":[{"id":"1145","span":{"begin":87,"end":90},"obj":"Gene"},{"id":"1146","span":{"begin":107,"end":110},"obj":"Gene"},{"id":"1147","span":{"begin":115,"end":118},"obj":"Gene"},{"id":"1148","span":{"begin":758,"end":764},"obj":"Gene"},{"id":"1149","span":{"begin":939,"end":947},"obj":"Gene"},{"id":"1150","span":{"begin":1256,"end":1264},"obj":"Gene"},{"id":"1151","span":{"begin":608,"end":613},"obj":"Species"},{"id":"1152","span":{"begin":1041,"end":1051},"obj":"Species"},{"id":"1153","span":{"begin":1225,"end":1235},"obj":"Species"},{"id":"1154","span":{"begin":1784,"end":1794},"obj":"Species"},{"id":"1155","span":{"begin":598,"end":606},"obj":"Species"},{"id":"1156","span":{"begin":740,"end":748},"obj":"Species"},{"id":"1157","span":{"begin":1161,"end":1169},"obj":"Species"},{"id":"1158","span":{"begin":1362,"end":1368},"obj":"Gene"},{"id":"1159","span":{"begin":1682,"end":1695},"obj":"Chemical"},{"id":"1160","span":{"begin":375,"end":383},"obj":"Disease"},{"id":"1161","span":{"begin":1533,"end":1557},"obj":"Disease"}],"attributes":[{"id":"A1145","pred":"tao:has_database_id","subj":"1145","obj":"Gene:5594"},{"id":"A1146","pred":"tao:has_database_id","subj":"1146","obj":"Gene:207"},{"id":"A1147","pred":"tao:has_database_id","subj":"1147","obj":"Gene:5594"},{"id":"A1148","pred":"tao:has_database_id","subj":"1148","obj":"Gene:10097"},{"id":"A1149","pred":"tao:has_database_id","subj":"1149","obj":"Gene:4651"},{"id":"A1150","pred":"tao:has_database_id","subj":"1150","obj":"Gene:4651"},{"id":"A1151","pred":"tao:has_database_id","subj":"1151","obj":"Tax:1570291"},{"id":"A1152","pred":"tao:has_database_id","subj":"1152","obj":"Tax:2697049"},{"id":"A1153","pred":"tao:has_database_id","subj":"1153","obj":"Tax:2697049"},{"id":"A1154","pred":"tao:has_database_id","subj":"1154","obj":"Tax:2697049"},{"id":"A1155","pred":"tao:has_database_id","subj":"1155","obj":"Tax:10245"},{"id":"A1156","pred":"tao:has_database_id","subj":"1156","obj":"Tax:10245"},{"id":"A1157","pred":"tao:has_database_id","subj":"1157","obj":"Tax:10245"},{"id":"A1158","pred":"tao:has_database_id","subj":"1158","obj":"Gene:79784"},{"id":"A1160","pred":"tao:has_database_id","subj":"1160","obj":"MESH:D007239"},{"id":"A1161","pred":"tao:has_database_id","subj":"1161","obj":"MESH:D014615"}],"namespaces":[{"prefix":"Tax","uri":"https://www.ncbi.nlm.nih.gov/taxonomy/"},{"prefix":"MESH","uri":"https://id.nlm.nih.gov/mesh/"},{"prefix":"Gene","uri":"https://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"CVCL","uri":"https://web.expasy.org/cellosaurus/CVCL_"}],"text":"The most strongly regulated kinases fall into a set of signaling pathways that include p38/MAPK signaling, AKT and ERK signaling, Rho GTPase and CK2 cytoskeleton signaling, and cell cycle regulation. The downregulation of ROCK and PAK kinase activity and upregulation of CK2 cytoskeleton-related targets suggest virus-induced changes in cytoskeleton organization. Imaging of infected cells revealed formation of actin-rich filopodia containing viral proteins. Higher-resolution electron microscopy data confirm the presence of assembled viral particles in these structures. Many viruses, including vaccinia, Ebola, and Marburg, hijack the host cell cytoskeleton to promote egress and rapid cell-to-cell spread across epithelial monolayers. Vaccinia promotes Arp2/3-dependent actin assembly, producing a filopodial protrusion with a virus at the tip (Leite and Way 2015). In contrast, Marburg virus hijacks the unconventional motor protein Myosin X, which promotes filopodium formation and trafficks the virus along the filopodium shaft. The SARS-CoV-2 protein clusters peppered throughout the length of filopodial protrusions more closely resemble Marburg than vaccinia, but additional work is required to understand whether SARS-CoV-2 makes use of either Myosin X motor activity or actin filament assembly to move along filopodia. CK2 is known to phosphorylate myosin proteins at endocytic sites to drive actin polymerization (Fernández-Golbano et al., 2014). Furthermore, CK2 has been found to regulate actin tail formation during vaccinia virus infection, enabling efficient cell-to-cell spread of the virus (Alvarez and Agaisse 2012; Smith and Law 2004). Here the CK2 inhibitor silmitasertib displayed robust antiviral activity, suggesting a role of this kinase in regulating the SARS-CoV-2 life cycle."}

{"project":"LitCovid-sentences","denotations":[{"id":"T338","span":{"begin":0,"end":199},"obj":"Sentence"},{"id":"T339","span":{"begin":200,"end":363},"obj":"Sentence"},{"id":"T340","span":{"begin":364,"end":459},"obj":"Sentence"},{"id":"T341","span":{"begin":460,"end":573},"obj":"Sentence"},{"id":"T342","span":{"begin":574,"end":739},"obj":"Sentence"},{"id":"T343","span":{"begin":740,"end":870},"obj":"Sentence"},{"id":"T344","span":{"begin":871,"end":1036},"obj":"Sentence"},{"id":"T345","span":{"begin":1037,"end":1331},"obj":"Sentence"},{"id":"T346","span":{"begin":1332,"end":1460},"obj":"Sentence"},{"id":"T347","span":{"begin":1461,"end":1658},"obj":"Sentence"},{"id":"T348","span":{"begin":1659,"end":1806},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"The most strongly regulated kinases fall into a set of signaling pathways that include p38/MAPK signaling, AKT and ERK signaling, Rho GTPase and CK2 cytoskeleton signaling, and cell cycle regulation. The downregulation of ROCK and PAK kinase activity and upregulation of CK2 cytoskeleton-related targets suggest virus-induced changes in cytoskeleton organization. Imaging of infected cells revealed formation of actin-rich filopodia containing viral proteins. Higher-resolution electron microscopy data confirm the presence of assembled viral particles in these structures. Many viruses, including vaccinia, Ebola, and Marburg, hijack the host cell cytoskeleton to promote egress and rapid cell-to-cell spread across epithelial monolayers. Vaccinia promotes Arp2/3-dependent actin assembly, producing a filopodial protrusion with a virus at the tip (Leite and Way 2015). In contrast, Marburg virus hijacks the unconventional motor protein Myosin X, which promotes filopodium formation and trafficks the virus along the filopodium shaft. The SARS-CoV-2 protein clusters peppered throughout the length of filopodial protrusions more closely resemble Marburg than vaccinia, but additional work is required to understand whether SARS-CoV-2 makes use of either Myosin X motor activity or actin filament assembly to move along filopodia. CK2 is known to phosphorylate myosin proteins at endocytic sites to drive actin polymerization (Fernández-Golbano et al., 2014). Furthermore, CK2 has been found to regulate actin tail formation during vaccinia virus infection, enabling efficient cell-to-cell spread of the virus (Alvarez and Agaisse 2012; Smith and Law 2004). Here the CK2 inhibitor silmitasertib displayed robust antiviral activity, suggesting a role of this kinase in regulating the SARS-CoV-2 life cycle."}

{"project":"2_test","denotations":[{"id":"32645325-25681743-20773080","span":{"begin":864,"end":868},"obj":"25681743"},{"id":"32645325-25268174-20773081","span":{"begin":1454,"end":1458},"obj":"25268174"},{"id":"32645325-22209233-20773082","span":{"begin":1632,"end":1636},"obj":"22209233"},{"id":"32645325-15567497-20773083","span":{"begin":1652,"end":1656},"obj":"15567497"}],"text":"The most strongly regulated kinases fall into a set of signaling pathways that include p38/MAPK signaling, AKT and ERK signaling, Rho GTPase and CK2 cytoskeleton signaling, and cell cycle regulation. The downregulation of ROCK and PAK kinase activity and upregulation of CK2 cytoskeleton-related targets suggest virus-induced changes in cytoskeleton organization. Imaging of infected cells revealed formation of actin-rich filopodia containing viral proteins. Higher-resolution electron microscopy data confirm the presence of assembled viral particles in these structures. Many viruses, including vaccinia, Ebola, and Marburg, hijack the host cell cytoskeleton to promote egress and rapid cell-to-cell spread across epithelial monolayers. Vaccinia promotes Arp2/3-dependent actin assembly, producing a filopodial protrusion with a virus at the tip (Leite and Way 2015). In contrast, Marburg virus hijacks the unconventional motor protein Myosin X, which promotes filopodium formation and trafficks the virus along the filopodium shaft. The SARS-CoV-2 protein clusters peppered throughout the length of filopodial protrusions more closely resemble Marburg than vaccinia, but additional work is required to understand whether SARS-CoV-2 makes use of either Myosin X motor activity or actin filament assembly to move along filopodia. CK2 is known to phosphorylate myosin proteins at endocytic sites to drive actin polymerization (Fernández-Golbano et al., 2014). Furthermore, CK2 has been found to regulate actin tail formation during vaccinia virus infection, enabling efficient cell-to-cell spread of the virus (Alvarez and Agaisse 2012; Smith and Law 2004). Here the CK2 inhibitor silmitasertib displayed robust antiviral activity, suggesting a role of this kinase in regulating the SARS-CoV-2 life cycle."}