PMC:7219429 / 10058-13415 JSON TXT

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LitCovid-PD-FMA-UBERON

LitCovid-PD-UBERON

{"project":"LitCovid-PD-UBERON","denotations":[{"id":"T3","span":{"begin":1227,"end":1231},"obj":"Body_part"},{"id":"T4","span":{"begin":2109,"end":2112},"obj":"Body_part"},{"id":"T5","span":{"begin":2745,"end":2748},"obj":"Body_part"},{"id":"T6","span":{"begin":3254,"end":3270},"obj":"Body_part"}],"attributes":[{"id":"A3","pred":"uberon_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/UBERON_0000025"},{"id":"A4","pred":"uberon_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/UBERON_2001840"},{"id":"A5","pred":"uberon_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/UBERON_2001840"},{"id":"A6","pred":"uberon_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/UBERON_4200047"}],"text":"3.1 Molecular mimicry between ATM and ganglioside GM1\nThe chemical structure of ATM is shown in Fig. 1 a. The molecule contains two sugar-like pyranyl rings, one with a nitrogen-containing group (N-pyr), the other with an acetyl group (Ac-pyr). The remaining part of the molecule is cyclic, so that its overall conformational flexibility, although significant, is restricted to a limited spatial volume of 2082 Å3 (Fig. 1b). Interestingly, this volume is almost the same as that of the saccharide part of ganglioside GM1 (2293 Å3, Fig. 1b), a lipid raft ganglioside that plays a critical role in the binding and endocytosis of respiratory viruses [26], including pathogenic human coronaviruses [27]. Beyond their similar spatial volume, the saccharide part of GM1 and ATM also share some analogous chemical features, including sugar rings and a solvent-accessible surface dotted with several CH and OH groups (Fig. 1b). This molecular similarity is further illustrated in Figure S1 where ATM is superimposed on the saccharide part of GM1.\nFig. 1 Structures of azithromycin (ATM) and SARS-CoV-2 spike protein trimer. (a) ATM, with both sugar-like pyranyl groups N-pyr and Ac-pyr indicated. The molecules are shown in chemical, tube and sphere rendering (carbon in green, nitrogen in blue, oxygen in red, hydrogen in white). (b) Molecular structure similarity between ATM and the saccharide part of ganglioside GM1. Both structures can adopt a globular shape the surface of which is covered with a patchwork of OH (arrows 1 and 2) and CH groups (arrow 3). The volume occupied by ATM and the saccharide part of GM1 can be estimated to be 2082 and 2293 Å3, respectively. (c) front and above views of the trimeric spike, each spike protein subunit with a distinct surface colour (cyan for chain A, yellow for chain B, purple for chain C). Atoms belonging to the ganglioside-binding domain of each subunit are visible underneath the slightly transparent surface. The ganglioside-binding domains, the NTD and the RBD are indicated.\nGiven that the SARS-CoV-2 spike protein displays a ganglioside-binding site at the tip of its NTD [10], the possibility that ATM, as a “ganglioside mimic”, could also bind to this site was considered. The structural features of the SARS-CoV-2 spike in the prefusion conformation [20] are shown in Fig. 1c. It consists of three interdigitated spike proteins that provide the virus its typical corona-like shape in electron microscopy images. In each subunit, the most distant part from the viral envelope is divided into two separate domains, the NTD and the RBD. The NTD has a flat surface available for ganglioside binding [10], and this process is independent from the ACE-2 receptor recognition, which occurs at the tip of the RBD [11,20]. When seen from above, the viral spike has a typical triangle shape, with a ganglioside-binding domain at each apex. Thus, the spike central area is devoted to ACE-2 binding, leaving three peripheric flat surface areas available for ganglioside attachment. Such dual ganglioside/receptor binding is commonly used by pathogenic viruses such as HIV-1 [28], [29], [30] and bacterial neurotoxins [16]. By combining the high affinity for a single protein receptor with multiple low affinity attachment sites, these pathogens have selected a very efficient pathway to gain entry into host cells."}

LitCovid-PD-MONDO

{"project":"LitCovid-PD-MONDO","denotations":[{"id":"T37","span":{"begin":1084,"end":1092},"obj":"Disease"},{"id":"T38","span":{"begin":1995,"end":1998},"obj":"Disease"},{"id":"T40","span":{"begin":2041,"end":2049},"obj":"Disease"},{"id":"T41","span":{"begin":2120,"end":2123},"obj":"Disease"},{"id":"T43","span":{"begin":2258,"end":2266},"obj":"Disease"},{"id":"T44","span":{"begin":2572,"end":2575},"obj":"Disease"},{"id":"T46","span":{"begin":2593,"end":2596},"obj":"Disease"}],"attributes":[{"id":"A37","pred":"mondo_id","subj":"T37","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A38","pred":"mondo_id","subj":"T38","obj":"http://purl.obolibrary.org/obo/MONDO_0008449"},{"id":"A39","pred":"mondo_id","subj":"T38","obj":"http://purl.obolibrary.org/obo/MONDO_0018075"},{"id":"A40","pred":"mondo_id","subj":"T40","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A41","pred":"mondo_id","subj":"T41","obj":"http://purl.obolibrary.org/obo/MONDO_0008449"},{"id":"A42","pred":"mondo_id","subj":"T41","obj":"http://purl.obolibrary.org/obo/MONDO_0018075"},{"id":"A43","pred":"mondo_id","subj":"T43","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A44","pred":"mondo_id","subj":"T44","obj":"http://purl.obolibrary.org/obo/MONDO_0008449"},{"id":"A45","pred":"mondo_id","subj":"T44","obj":"http://purl.obolibrary.org/obo/MONDO_0018075"},{"id":"A46","pred":"mondo_id","subj":"T46","obj":"http://purl.obolibrary.org/obo/MONDO_0008449"},{"id":"A47","pred":"mondo_id","subj":"T46","obj":"http://purl.obolibrary.org/obo/MONDO_0018075"}],"text":"3.1 Molecular mimicry between ATM and ganglioside GM1\nThe chemical structure of ATM is shown in Fig. 1 a. The molecule contains two sugar-like pyranyl rings, one with a nitrogen-containing group (N-pyr), the other with an acetyl group (Ac-pyr). The remaining part of the molecule is cyclic, so that its overall conformational flexibility, although significant, is restricted to a limited spatial volume of 2082 Å3 (Fig. 1b). Interestingly, this volume is almost the same as that of the saccharide part of ganglioside GM1 (2293 Å3, Fig. 1b), a lipid raft ganglioside that plays a critical role in the binding and endocytosis of respiratory viruses [26], including pathogenic human coronaviruses [27]. Beyond their similar spatial volume, the saccharide part of GM1 and ATM also share some analogous chemical features, including sugar rings and a solvent-accessible surface dotted with several CH and OH groups (Fig. 1b). This molecular similarity is further illustrated in Figure S1 where ATM is superimposed on the saccharide part of GM1.\nFig. 1 Structures of azithromycin (ATM) and SARS-CoV-2 spike protein trimer. (a) ATM, with both sugar-like pyranyl groups N-pyr and Ac-pyr indicated. The molecules are shown in chemical, tube and sphere rendering (carbon in green, nitrogen in blue, oxygen in red, hydrogen in white). (b) Molecular structure similarity between ATM and the saccharide part of ganglioside GM1. Both structures can adopt a globular shape the surface of which is covered with a patchwork of OH (arrows 1 and 2) and CH groups (arrow 3). The volume occupied by ATM and the saccharide part of GM1 can be estimated to be 2082 and 2293 Å3, respectively. (c) front and above views of the trimeric spike, each spike protein subunit with a distinct surface colour (cyan for chain A, yellow for chain B, purple for chain C). Atoms belonging to the ganglioside-binding domain of each subunit are visible underneath the slightly transparent surface. The ganglioside-binding domains, the NTD and the RBD are indicated.\nGiven that the SARS-CoV-2 spike protein displays a ganglioside-binding site at the tip of its NTD [10], the possibility that ATM, as a “ganglioside mimic”, could also bind to this site was considered. The structural features of the SARS-CoV-2 spike in the prefusion conformation [20] are shown in Fig. 1c. It consists of three interdigitated spike proteins that provide the virus its typical corona-like shape in electron microscopy images. In each subunit, the most distant part from the viral envelope is divided into two separate domains, the NTD and the RBD. The NTD has a flat surface available for ganglioside binding [10], and this process is independent from the ACE-2 receptor recognition, which occurs at the tip of the RBD [11,20]. When seen from above, the viral spike has a typical triangle shape, with a ganglioside-binding domain at each apex. Thus, the spike central area is devoted to ACE-2 binding, leaving three peripheric flat surface areas available for ganglioside attachment. Such dual ganglioside/receptor binding is commonly used by pathogenic viruses such as HIV-1 [28], [29], [30] and bacterial neurotoxins [16]. By combining the high affinity for a single protein receptor with multiple low affinity attachment sites, these pathogens have selected a very efficient pathway to gain entry into host cells."}

LitCovid-PD-CLO

LitCovid-PD-CHEBI

LitCovid-PD-GO-BP

{"project":"LitCovid-PD-GO-BP","denotations":[{"id":"T3","span":{"begin":613,"end":624},"obj":"http://purl.obolibrary.org/obo/GO_0006897"},{"id":"T4","span":{"begin":3335,"end":3350},"obj":"http://purl.obolibrary.org/obo/GO_0044409"}],"text":"3.1 Molecular mimicry between ATM and ganglioside GM1\nThe chemical structure of ATM is shown in Fig. 1 a. The molecule contains two sugar-like pyranyl rings, one with a nitrogen-containing group (N-pyr), the other with an acetyl group (Ac-pyr). The remaining part of the molecule is cyclic, so that its overall conformational flexibility, although significant, is restricted to a limited spatial volume of 2082 Å3 (Fig. 1b). Interestingly, this volume is almost the same as that of the saccharide part of ganglioside GM1 (2293 Å3, Fig. 1b), a lipid raft ganglioside that plays a critical role in the binding and endocytosis of respiratory viruses [26], including pathogenic human coronaviruses [27]. Beyond their similar spatial volume, the saccharide part of GM1 and ATM also share some analogous chemical features, including sugar rings and a solvent-accessible surface dotted with several CH and OH groups (Fig. 1b). This molecular similarity is further illustrated in Figure S1 where ATM is superimposed on the saccharide part of GM1.\nFig. 1 Structures of azithromycin (ATM) and SARS-CoV-2 spike protein trimer. (a) ATM, with both sugar-like pyranyl groups N-pyr and Ac-pyr indicated. The molecules are shown in chemical, tube and sphere rendering (carbon in green, nitrogen in blue, oxygen in red, hydrogen in white). (b) Molecular structure similarity between ATM and the saccharide part of ganglioside GM1. Both structures can adopt a globular shape the surface of which is covered with a patchwork of OH (arrows 1 and 2) and CH groups (arrow 3). The volume occupied by ATM and the saccharide part of GM1 can be estimated to be 2082 and 2293 Å3, respectively. (c) front and above views of the trimeric spike, each spike protein subunit with a distinct surface colour (cyan for chain A, yellow for chain B, purple for chain C). Atoms belonging to the ganglioside-binding domain of each subunit are visible underneath the slightly transparent surface. The ganglioside-binding domains, the NTD and the RBD are indicated.\nGiven that the SARS-CoV-2 spike protein displays a ganglioside-binding site at the tip of its NTD [10], the possibility that ATM, as a “ganglioside mimic”, could also bind to this site was considered. The structural features of the SARS-CoV-2 spike in the prefusion conformation [20] are shown in Fig. 1c. It consists of three interdigitated spike proteins that provide the virus its typical corona-like shape in electron microscopy images. In each subunit, the most distant part from the viral envelope is divided into two separate domains, the NTD and the RBD. The NTD has a flat surface available for ganglioside binding [10], and this process is independent from the ACE-2 receptor recognition, which occurs at the tip of the RBD [11,20]. When seen from above, the viral spike has a typical triangle shape, with a ganglioside-binding domain at each apex. Thus, the spike central area is devoted to ACE-2 binding, leaving three peripheric flat surface areas available for ganglioside attachment. Such dual ganglioside/receptor binding is commonly used by pathogenic viruses such as HIV-1 [28], [29], [30] and bacterial neurotoxins [16]. By combining the high affinity for a single protein receptor with multiple low affinity attachment sites, these pathogens have selected a very efficient pathway to gain entry into host cells."}

LitCovid-PD-GlycoEpitope

{"project":"LitCovid-PD-GlycoEpitope","denotations":[{"id":"T10","span":{"begin":51,"end":54},"obj":"GlycoEpitope"},{"id":"T11","span":{"begin":518,"end":521},"obj":"GlycoEpitope"},{"id":"T12","span":{"begin":761,"end":764},"obj":"GlycoEpitope"},{"id":"T13","span":{"begin":1035,"end":1038},"obj":"GlycoEpitope"},{"id":"T14","span":{"begin":1410,"end":1413},"obj":"GlycoEpitope"},{"id":"T15","span":{"begin":1609,"end":1612},"obj":"GlycoEpitope"}],"attributes":[{"id":"A10","pred":"glyco_epitope_db_id","subj":"T10","obj":"http://www.glycoepitope.jp/epitopes/EP0050"},{"id":"A11","pred":"glyco_epitope_db_id","subj":"T11","obj":"http://www.glycoepitope.jp/epitopes/EP0050"},{"id":"A12","pred":"glyco_epitope_db_id","subj":"T12","obj":"http://www.glycoepitope.jp/epitopes/EP0050"},{"id":"A13","pred":"glyco_epitope_db_id","subj":"T13","obj":"http://www.glycoepitope.jp/epitopes/EP0050"},{"id":"A14","pred":"glyco_epitope_db_id","subj":"T14","obj":"http://www.glycoepitope.jp/epitopes/EP0050"},{"id":"A15","pred":"glyco_epitope_db_id","subj":"T15","obj":"http://www.glycoepitope.jp/epitopes/EP0050"}],"text":"3.1 Molecular mimicry between ATM and ganglioside GM1\nThe chemical structure of ATM is shown in Fig. 1 a. The molecule contains two sugar-like pyranyl rings, one with a nitrogen-containing group (N-pyr), the other with an acetyl group (Ac-pyr). The remaining part of the molecule is cyclic, so that its overall conformational flexibility, although significant, is restricted to a limited spatial volume of 2082 Å3 (Fig. 1b). Interestingly, this volume is almost the same as that of the saccharide part of ganglioside GM1 (2293 Å3, Fig. 1b), a lipid raft ganglioside that plays a critical role in the binding and endocytosis of respiratory viruses [26], including pathogenic human coronaviruses [27]. Beyond their similar spatial volume, the saccharide part of GM1 and ATM also share some analogous chemical features, including sugar rings and a solvent-accessible surface dotted with several CH and OH groups (Fig. 1b). This molecular similarity is further illustrated in Figure S1 where ATM is superimposed on the saccharide part of GM1.\nFig. 1 Structures of azithromycin (ATM) and SARS-CoV-2 spike protein trimer. (a) ATM, with both sugar-like pyranyl groups N-pyr and Ac-pyr indicated. The molecules are shown in chemical, tube and sphere rendering (carbon in green, nitrogen in blue, oxygen in red, hydrogen in white). (b) Molecular structure similarity between ATM and the saccharide part of ganglioside GM1. Both structures can adopt a globular shape the surface of which is covered with a patchwork of OH (arrows 1 and 2) and CH groups (arrow 3). The volume occupied by ATM and the saccharide part of GM1 can be estimated to be 2082 and 2293 Å3, respectively. (c) front and above views of the trimeric spike, each spike protein subunit with a distinct surface colour (cyan for chain A, yellow for chain B, purple for chain C). Atoms belonging to the ganglioside-binding domain of each subunit are visible underneath the slightly transparent surface. The ganglioside-binding domains, the NTD and the RBD are indicated.\nGiven that the SARS-CoV-2 spike protein displays a ganglioside-binding site at the tip of its NTD [10], the possibility that ATM, as a “ganglioside mimic”, could also bind to this site was considered. The structural features of the SARS-CoV-2 spike in the prefusion conformation [20] are shown in Fig. 1c. It consists of three interdigitated spike proteins that provide the virus its typical corona-like shape in electron microscopy images. In each subunit, the most distant part from the viral envelope is divided into two separate domains, the NTD and the RBD. The NTD has a flat surface available for ganglioside binding [10], and this process is independent from the ACE-2 receptor recognition, which occurs at the tip of the RBD [11,20]. When seen from above, the viral spike has a typical triangle shape, with a ganglioside-binding domain at each apex. Thus, the spike central area is devoted to ACE-2 binding, leaving three peripheric flat surface areas available for ganglioside attachment. Such dual ganglioside/receptor binding is commonly used by pathogenic viruses such as HIV-1 [28], [29], [30] and bacterial neurotoxins [16]. By combining the high affinity for a single protein receptor with multiple low affinity attachment sites, these pathogens have selected a very efficient pathway to gain entry into host cells."}

LitCovid-sentences

{"project":"LitCovid-sentences","denotations":[{"id":"T75","span":{"begin":0,"end":54},"obj":"Sentence"},{"id":"T76","span":{"begin":55,"end":106},"obj":"Sentence"},{"id":"T77","span":{"begin":107,"end":245},"obj":"Sentence"},{"id":"T78","span":{"begin":246,"end":425},"obj":"Sentence"},{"id":"T79","span":{"begin":426,"end":700},"obj":"Sentence"},{"id":"T80","span":{"begin":701,"end":920},"obj":"Sentence"},{"id":"T81","span":{"begin":921,"end":1039},"obj":"Sentence"},{"id":"T82","span":{"begin":1040,"end":1189},"obj":"Sentence"},{"id":"T83","span":{"begin":1190,"end":1414},"obj":"Sentence"},{"id":"T84","span":{"begin":1415,"end":1554},"obj":"Sentence"},{"id":"T85","span":{"begin":1555,"end":1834},"obj":"Sentence"},{"id":"T86","span":{"begin":1835,"end":1957},"obj":"Sentence"},{"id":"T87","span":{"begin":1958,"end":2025},"obj":"Sentence"},{"id":"T88","span":{"begin":2026,"end":2226},"obj":"Sentence"},{"id":"T89","span":{"begin":2227,"end":2331},"obj":"Sentence"},{"id":"T90","span":{"begin":2332,"end":2466},"obj":"Sentence"},{"id":"T91","span":{"begin":2467,"end":2588},"obj":"Sentence"},{"id":"T92","span":{"begin":2589,"end":2768},"obj":"Sentence"},{"id":"T93","span":{"begin":2769,"end":2884},"obj":"Sentence"},{"id":"T94","span":{"begin":2885,"end":3024},"obj":"Sentence"},{"id":"T95","span":{"begin":3025,"end":3165},"obj":"Sentence"},{"id":"T96","span":{"begin":3166,"end":3357},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"3.1 Molecular mimicry between ATM and ganglioside GM1\nThe chemical structure of ATM is shown in Fig. 1 a. The molecule contains two sugar-like pyranyl rings, one with a nitrogen-containing group (N-pyr), the other with an acetyl group (Ac-pyr). The remaining part of the molecule is cyclic, so that its overall conformational flexibility, although significant, is restricted to a limited spatial volume of 2082 Å3 (Fig. 1b). Interestingly, this volume is almost the same as that of the saccharide part of ganglioside GM1 (2293 Å3, Fig. 1b), a lipid raft ganglioside that plays a critical role in the binding and endocytosis of respiratory viruses [26], including pathogenic human coronaviruses [27]. Beyond their similar spatial volume, the saccharide part of GM1 and ATM also share some analogous chemical features, including sugar rings and a solvent-accessible surface dotted with several CH and OH groups (Fig. 1b). This molecular similarity is further illustrated in Figure S1 where ATM is superimposed on the saccharide part of GM1.\nFig. 1 Structures of azithromycin (ATM) and SARS-CoV-2 spike protein trimer. (a) ATM, with both sugar-like pyranyl groups N-pyr and Ac-pyr indicated. The molecules are shown in chemical, tube and sphere rendering (carbon in green, nitrogen in blue, oxygen in red, hydrogen in white). (b) Molecular structure similarity between ATM and the saccharide part of ganglioside GM1. Both structures can adopt a globular shape the surface of which is covered with a patchwork of OH (arrows 1 and 2) and CH groups (arrow 3). The volume occupied by ATM and the saccharide part of GM1 can be estimated to be 2082 and 2293 Å3, respectively. (c) front and above views of the trimeric spike, each spike protein subunit with a distinct surface colour (cyan for chain A, yellow for chain B, purple for chain C). Atoms belonging to the ganglioside-binding domain of each subunit are visible underneath the slightly transparent surface. The ganglioside-binding domains, the NTD and the RBD are indicated.\nGiven that the SARS-CoV-2 spike protein displays a ganglioside-binding site at the tip of its NTD [10], the possibility that ATM, as a “ganglioside mimic”, could also bind to this site was considered. The structural features of the SARS-CoV-2 spike in the prefusion conformation [20] are shown in Fig. 1c. It consists of three interdigitated spike proteins that provide the virus its typical corona-like shape in electron microscopy images. In each subunit, the most distant part from the viral envelope is divided into two separate domains, the NTD and the RBD. The NTD has a flat surface available for ganglioside binding [10], and this process is independent from the ACE-2 receptor recognition, which occurs at the tip of the RBD [11,20]. When seen from above, the viral spike has a typical triangle shape, with a ganglioside-binding domain at each apex. Thus, the spike central area is devoted to ACE-2 binding, leaving three peripheric flat surface areas available for ganglioside attachment. Such dual ganglioside/receptor binding is commonly used by pathogenic viruses such as HIV-1 [28], [29], [30] and bacterial neurotoxins [16]. By combining the high affinity for a single protein receptor with multiple low affinity attachment sites, these pathogens have selected a very efficient pathway to gain entry into host cells."}

LitCovid-PubTator

2_test

{"project":"2_test","denotations":[{"id":"32405156-18279660-48151022","span":{"begin":696,"end":698},"obj":"18279660"},{"id":"32405156-32075877-48151023","span":{"begin":2306,"end":2308},"obj":"32075877"},{"id":"32405156-32132184-48151024","span":{"begin":2761,"end":2763},"obj":"32132184"},{"id":"32405156-32075877-48151025","span":{"begin":2764,"end":2766},"obj":"32075877"},{"id":"32405156-31431523-48151026","span":{"begin":3161,"end":3163},"obj":"31431523"},{"id":"T61528","span":{"begin":696,"end":698},"obj":"18279660"},{"id":"T54896","span":{"begin":2306,"end":2308},"obj":"32075877"},{"id":"T86066","span":{"begin":2761,"end":2763},"obj":"32132184"},{"id":"T70176","span":{"begin":2764,"end":2766},"obj":"32075877"},{"id":"T42537","span":{"begin":3161,"end":3163},"obj":"31431523"}],"text":"3.1 Molecular mimicry between ATM and ganglioside GM1\nThe chemical structure of ATM is shown in Fig. 1 a. The molecule contains two sugar-like pyranyl rings, one with a nitrogen-containing group (N-pyr), the other with an acetyl group (Ac-pyr). The remaining part of the molecule is cyclic, so that its overall conformational flexibility, although significant, is restricted to a limited spatial volume of 2082 Å3 (Fig. 1b). Interestingly, this volume is almost the same as that of the saccharide part of ganglioside GM1 (2293 Å3, Fig. 1b), a lipid raft ganglioside that plays a critical role in the binding and endocytosis of respiratory viruses [26], including pathogenic human coronaviruses [27]. Beyond their similar spatial volume, the saccharide part of GM1 and ATM also share some analogous chemical features, including sugar rings and a solvent-accessible surface dotted with several CH and OH groups (Fig. 1b). This molecular similarity is further illustrated in Figure S1 where ATM is superimposed on the saccharide part of GM1.\nFig. 1 Structures of azithromycin (ATM) and SARS-CoV-2 spike protein trimer. (a) ATM, with both sugar-like pyranyl groups N-pyr and Ac-pyr indicated. The molecules are shown in chemical, tube and sphere rendering (carbon in green, nitrogen in blue, oxygen in red, hydrogen in white). (b) Molecular structure similarity between ATM and the saccharide part of ganglioside GM1. Both structures can adopt a globular shape the surface of which is covered with a patchwork of OH (arrows 1 and 2) and CH groups (arrow 3). The volume occupied by ATM and the saccharide part of GM1 can be estimated to be 2082 and 2293 Å3, respectively. (c) front and above views of the trimeric spike, each spike protein subunit with a distinct surface colour (cyan for chain A, yellow for chain B, purple for chain C). Atoms belonging to the ganglioside-binding domain of each subunit are visible underneath the slightly transparent surface. The ganglioside-binding domains, the NTD and the RBD are indicated.\nGiven that the SARS-CoV-2 spike protein displays a ganglioside-binding site at the tip of its NTD [10], the possibility that ATM, as a “ganglioside mimic”, could also bind to this site was considered. The structural features of the SARS-CoV-2 spike in the prefusion conformation [20] are shown in Fig. 1c. It consists of three interdigitated spike proteins that provide the virus its typical corona-like shape in electron microscopy images. In each subunit, the most distant part from the viral envelope is divided into two separate domains, the NTD and the RBD. The NTD has a flat surface available for ganglioside binding [10], and this process is independent from the ACE-2 receptor recognition, which occurs at the tip of the RBD [11,20]. When seen from above, the viral spike has a typical triangle shape, with a ganglioside-binding domain at each apex. Thus, the spike central area is devoted to ACE-2 binding, leaving three peripheric flat surface areas available for ganglioside attachment. Such dual ganglioside/receptor binding is commonly used by pathogenic viruses such as HIV-1 [28], [29], [30] and bacterial neurotoxins [16]. By combining the high affinity for a single protein receptor with multiple low affinity attachment sites, these pathogens have selected a very efficient pathway to gain entry into host cells."}

PMC:7219429 / 10058-13415 JSONTXT

Annnotations TAB JSON ListView MergeView

PMC:7219429 / 10058-13415 JSON TXT