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LitCovid-PD-FMA-UBERON

LitCovid-PD-UBERON

{"project":"LitCovid-PD-UBERON","denotations":[{"id":"T1","span":{"begin":1260,"end":1264},"obj":"Body_part"},{"id":"T2","span":{"begin":1299,"end":1317},"obj":"Body_part"},{"id":"T3","span":{"begin":1308,"end":1317},"obj":"Body_part"},{"id":"T4","span":{"begin":1322,"end":1331},"obj":"Body_part"},{"id":"T5","span":{"begin":1736,"end":1755},"obj":"Body_part"},{"id":"T6","span":{"begin":2406,"end":2421},"obj":"Body_part"},{"id":"T7","span":{"begin":2416,"end":2421},"obj":"Body_part"},{"id":"T8","span":{"begin":2536,"end":2556},"obj":"Body_part"},{"id":"T9","span":{"begin":2546,"end":2556},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"A2","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/UBERON_0004821"},{"id":"A3","pred":"uberon_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/UBERON_0000483"},{"id":"A4","pred":"uberon_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/UBERON_0001982"},{"id":"A5","pred":"uberon_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/UBERON_0002707"},{"id":"A6","pred":"uberon_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/UBERON_0001579"},{"id":"A7","pred":"uberon_id","subj":"T7","obj":"http://purl.obolibrary.org/obo/UBERON_0001021"},{"id":"A8","pred":"uberon_id","subj":"T8","obj":"http://purl.obolibrary.org/obo/UBERON_0001997"},{"id":"A9","pred":"uberon_id","subj":"T9","obj":"http://purl.obolibrary.org/obo/UBERON_0000483"}],"text":"Background\nThe emergence of the novel β-coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a global pandemic of coronavirus disease 2019 (COVID-19) [1]. Currently, in mid-May 2020, there are over 4,000,000 confirmed cases of COVID-19 and over 300,000 deaths due to COVID-19 worldwide, according to the COVID-19 Dashboard by the Center for Systems Science and Engineering at Johns Hopkins University (https://coronavirus.jhu.edu/map.html).\nThere is now increasing collaborative activity by governments, academic institutions, biotechnology companies, and the pharmaceutical industry to investigate the range of possible treatments for COVID-19 and vaccines to prevent infection from SARS-CoV-2 [1]. Current approaches are drawing on previous studies on severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome (MERS-CoV) [1]. For example, studies have shown that SARS-CoV and SARS-CoV-2 have structural similarities within their respective receptor-binding domains (RBDs) of the S1 spike protein subunit that mediate strong multi-point binding to the extracellular globular domain of angiotensin-converting enzyme-2 (ACE2), which may involve neurological expression [2–9]. Within the lung, widespread expression of ACE2 by alveolar epithelia and capillary cells facilitates viral infection via internalization and replication, leading to severe respiratory disease [2,3]. Recent evidence of co-morbid neurological sequelae of SARS-CoV-2 infection has been reported in the presence or absence of severe respiratory disease where patients have presented with symptoms of nausea, vomiting, anosmia, loss of taste, impaired consciousness, agitation and confusion, corticospinal tract signs, and cerebrovascular diseases, including encephalopathy [5–7].\nAs discussed below, a significant body of empirical studies has demonstrated that the destructive neurological effects of rabies virus (RABV) infections are mediated by CNS transport of the virus tightly bound to the nicotinic acetylcholine receptor (nAChR). It has also been recently hypothesized that a similar mechanism may exist to explain the multiple neurological effects of SARS-CoV-2 via binding to peripheral nAChRs followed by orthograde or retrograde transport into the CNS [10,11]. Potential portals for transport of SARS-CoV-2/nAChR complexes into the CNS include the olfactory nerve and primary olfactory neurons [9,12], and/or peripheral trigeminal sensory terminal structures located within the olfactory epithelium [13,14]. Further studies are required to fully test the hypothesis that the nAChR receptor represents an obligate biochemical chaperone or effector protein responsible for transport of infective SARS-CoV-2 particles into discrete CNS areas. As a corollary, pharmacological targeting of SARS-CoV-2/nAChR complexes may represent a novel vehicle for prevention and control of neurological comorbidities of COVID-19 infection [10]. There is the potential for new clinical trials to investigate nicotine as a means of blocking SARS-CoV-2-nAChR binding to prevent or treat COVID-19 (https://www.theguardian.com/world/2020/apr/22/french-study-suggests-smokers-at-lower-risk-of-getting-coronavirus). As such, we present a critical discussion that integrates lessons learned from prior RABV research and vaccine development into a working model of a SARS-CoV-2 vaccine that selectively targets and neutralizes CNS penetration of a tightly bound viral nAChR complex."}

LitCovid-PubTator

LitCovid-PD-MONDO

LitCovid-PD-CLO

LitCovid-PD-CHEBI

{"project":"LitCovid-PD-CHEBI","denotations":[{"id":"T5","span":{"begin":598,"end":612},"obj":"Chemical"},{"id":"T6","span":{"begin":1064,"end":1071},"obj":"Chemical"},{"id":"T7","span":{"begin":1160,"end":1171},"obj":"Chemical"},{"id":"T8","span":{"begin":2052,"end":2065},"obj":"Chemical"},{"id":"T9","span":{"begin":2696,"end":2704},"obj":"Chemical"},{"id":"T10","span":{"begin":2705,"end":2712},"obj":"Chemical"},{"id":"T11","span":{"begin":3047,"end":3055},"obj":"Chemical"}],"attributes":[{"id":"A5","pred":"chebi_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/CHEBI_52217"},{"id":"A6","pred":"chebi_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"id":"A7","pred":"chebi_id","subj":"T7","obj":"http://purl.obolibrary.org/obo/CHEBI_48433"},{"id":"A8","pred":"chebi_id","subj":"T8","obj":"http://purl.obolibrary.org/obo/CHEBI_15355"},{"id":"A9","pred":"chebi_id","subj":"T9","obj":"http://purl.obolibrary.org/obo/CHEBI_35224"},{"id":"A10","pred":"chebi_id","subj":"T10","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"id":"A11","pred":"chebi_id","subj":"T11","obj":"http://purl.obolibrary.org/obo/CHEBI_18723"}],"text":"Background\nThe emergence of the novel β-coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a global pandemic of coronavirus disease 2019 (COVID-19) [1]. Currently, in mid-May 2020, there are over 4,000,000 confirmed cases of COVID-19 and over 300,000 deaths due to COVID-19 worldwide, according to the COVID-19 Dashboard by the Center for Systems Science and Engineering at Johns Hopkins University (https://coronavirus.jhu.edu/map.html).\nThere is now increasing collaborative activity by governments, academic institutions, biotechnology companies, and the pharmaceutical industry to investigate the range of possible treatments for COVID-19 and vaccines to prevent infection from SARS-CoV-2 [1]. Current approaches are drawing on previous studies on severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome (MERS-CoV) [1]. For example, studies have shown that SARS-CoV and SARS-CoV-2 have structural similarities within their respective receptor-binding domains (RBDs) of the S1 spike protein subunit that mediate strong multi-point binding to the extracellular globular domain of angiotensin-converting enzyme-2 (ACE2), which may involve neurological expression [2–9]. Within the lung, widespread expression of ACE2 by alveolar epithelia and capillary cells facilitates viral infection via internalization and replication, leading to severe respiratory disease [2,3]. Recent evidence of co-morbid neurological sequelae of SARS-CoV-2 infection has been reported in the presence or absence of severe respiratory disease where patients have presented with symptoms of nausea, vomiting, anosmia, loss of taste, impaired consciousness, agitation and confusion, corticospinal tract signs, and cerebrovascular diseases, including encephalopathy [5–7].\nAs discussed below, a significant body of empirical studies has demonstrated that the destructive neurological effects of rabies virus (RABV) infections are mediated by CNS transport of the virus tightly bound to the nicotinic acetylcholine receptor (nAChR). It has also been recently hypothesized that a similar mechanism may exist to explain the multiple neurological effects of SARS-CoV-2 via binding to peripheral nAChRs followed by orthograde or retrograde transport into the CNS [10,11]. Potential portals for transport of SARS-CoV-2/nAChR complexes into the CNS include the olfactory nerve and primary olfactory neurons [9,12], and/or peripheral trigeminal sensory terminal structures located within the olfactory epithelium [13,14]. Further studies are required to fully test the hypothesis that the nAChR receptor represents an obligate biochemical chaperone or effector protein responsible for transport of infective SARS-CoV-2 particles into discrete CNS areas. As a corollary, pharmacological targeting of SARS-CoV-2/nAChR complexes may represent a novel vehicle for prevention and control of neurological comorbidities of COVID-19 infection [10]. There is the potential for new clinical trials to investigate nicotine as a means of blocking SARS-CoV-2-nAChR binding to prevent or treat COVID-19 (https://www.theguardian.com/world/2020/apr/22/french-study-suggests-smokers-at-lower-risk-of-getting-coronavirus). As such, we present a critical discussion that integrates lessons learned from prior RABV research and vaccine development into a working model of a SARS-CoV-2 vaccine that selectively targets and neutralizes CNS penetration of a tightly bound viral nAChR complex."}

LitCovid-PD-GO-BP

{"project":"LitCovid-PD-GO-BP","denotations":[{"id":"T6","span":{"begin":1350,"end":1365},"obj":"http://purl.obolibrary.org/obo/GO_0016032"},{"id":"T7","span":{"begin":1680,"end":1685},"obj":"http://purl.obolibrary.org/obo/GO_0050909"},{"id":"T8","span":{"begin":1998,"end":2020},"obj":"http://purl.obolibrary.org/obo/GO_0046794"},{"id":"T9","span":{"begin":1998,"end":2007},"obj":"http://purl.obolibrary.org/obo/GO_0006810"},{"id":"T10","span":{"begin":2076,"end":2081},"obj":"http://purl.obolibrary.org/obo/GO_0022848"},{"id":"T11","span":{"begin":2287,"end":2296},"obj":"http://purl.obolibrary.org/obo/GO_0006810"},{"id":"T12","span":{"begin":2341,"end":2350},"obj":"http://purl.obolibrary.org/obo/GO_0006810"},{"id":"T13","span":{"begin":2365,"end":2370},"obj":"http://purl.obolibrary.org/obo/GO_0022848"},{"id":"T14","span":{"begin":2633,"end":2638},"obj":"http://purl.obolibrary.org/obo/GO_0022848"},{"id":"T15","span":{"begin":2729,"end":2738},"obj":"http://purl.obolibrary.org/obo/GO_0006810"},{"id":"T16","span":{"begin":2854,"end":2859},"obj":"http://purl.obolibrary.org/obo/GO_0022848"},{"id":"T17","span":{"begin":3090,"end":3095},"obj":"http://purl.obolibrary.org/obo/GO_0022848"},{"id":"T18","span":{"begin":3499,"end":3504},"obj":"http://purl.obolibrary.org/obo/GO_0022848"}],"text":"Background\nThe emergence of the novel β-coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a global pandemic of coronavirus disease 2019 (COVID-19) [1]. Currently, in mid-May 2020, there are over 4,000,000 confirmed cases of COVID-19 and over 300,000 deaths due to COVID-19 worldwide, according to the COVID-19 Dashboard by the Center for Systems Science and Engineering at Johns Hopkins University (https://coronavirus.jhu.edu/map.html).\nThere is now increasing collaborative activity by governments, academic institutions, biotechnology companies, and the pharmaceutical industry to investigate the range of possible treatments for COVID-19 and vaccines to prevent infection from SARS-CoV-2 [1]. Current approaches are drawing on previous studies on severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome (MERS-CoV) [1]. For example, studies have shown that SARS-CoV and SARS-CoV-2 have structural similarities within their respective receptor-binding domains (RBDs) of the S1 spike protein subunit that mediate strong multi-point binding to the extracellular globular domain of angiotensin-converting enzyme-2 (ACE2), which may involve neurological expression [2–9]. Within the lung, widespread expression of ACE2 by alveolar epithelia and capillary cells facilitates viral infection via internalization and replication, leading to severe respiratory disease [2,3]. Recent evidence of co-morbid neurological sequelae of SARS-CoV-2 infection has been reported in the presence or absence of severe respiratory disease where patients have presented with symptoms of nausea, vomiting, anosmia, loss of taste, impaired consciousness, agitation and confusion, corticospinal tract signs, and cerebrovascular diseases, including encephalopathy [5–7].\nAs discussed below, a significant body of empirical studies has demonstrated that the destructive neurological effects of rabies virus (RABV) infections are mediated by CNS transport of the virus tightly bound to the nicotinic acetylcholine receptor (nAChR). It has also been recently hypothesized that a similar mechanism may exist to explain the multiple neurological effects of SARS-CoV-2 via binding to peripheral nAChRs followed by orthograde or retrograde transport into the CNS [10,11]. Potential portals for transport of SARS-CoV-2/nAChR complexes into the CNS include the olfactory nerve and primary olfactory neurons [9,12], and/or peripheral trigeminal sensory terminal structures located within the olfactory epithelium [13,14]. Further studies are required to fully test the hypothesis that the nAChR receptor represents an obligate biochemical chaperone or effector protein responsible for transport of infective SARS-CoV-2 particles into discrete CNS areas. As a corollary, pharmacological targeting of SARS-CoV-2/nAChR complexes may represent a novel vehicle for prevention and control of neurological comorbidities of COVID-19 infection [10]. There is the potential for new clinical trials to investigate nicotine as a means of blocking SARS-CoV-2-nAChR binding to prevent or treat COVID-19 (https://www.theguardian.com/world/2020/apr/22/french-study-suggests-smokers-at-lower-risk-of-getting-coronavirus). As such, we present a critical discussion that integrates lessons learned from prior RABV research and vaccine development into a working model of a SARS-CoV-2 vaccine that selectively targets and neutralizes CNS penetration of a tightly bound viral nAChR complex."}

LitCovid-sentences

{"project":"LitCovid-sentences","denotations":[{"id":"T10","span":{"begin":0,"end":10},"obj":"Sentence"},{"id":"T11","span":{"begin":11,"end":192},"obj":"Sentence"},{"id":"T12","span":{"begin":193,"end":478},"obj":"Sentence"},{"id":"T13","span":{"begin":479,"end":737},"obj":"Sentence"},{"id":"T14","span":{"begin":738,"end":901},"obj":"Sentence"},{"id":"T15","span":{"begin":902,"end":1248},"obj":"Sentence"},{"id":"T16","span":{"begin":1249,"end":1447},"obj":"Sentence"},{"id":"T17","span":{"begin":1448,"end":1824},"obj":"Sentence"},{"id":"T18","span":{"begin":1825,"end":2083},"obj":"Sentence"},{"id":"T19","span":{"begin":2084,"end":2318},"obj":"Sentence"},{"id":"T20","span":{"begin":2319,"end":2565},"obj":"Sentence"},{"id":"T21","span":{"begin":2566,"end":2797},"obj":"Sentence"},{"id":"T22","span":{"begin":2798,"end":2984},"obj":"Sentence"},{"id":"T23","span":{"begin":2985,"end":3248},"obj":"Sentence"},{"id":"T24","span":{"begin":3249,"end":3513},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"Background\nThe emergence of the novel β-coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a global pandemic of coronavirus disease 2019 (COVID-19) [1]. Currently, in mid-May 2020, there are over 4,000,000 confirmed cases of COVID-19 and over 300,000 deaths due to COVID-19 worldwide, according to the COVID-19 Dashboard by the Center for Systems Science and Engineering at Johns Hopkins University (https://coronavirus.jhu.edu/map.html).\nThere is now increasing collaborative activity by governments, academic institutions, biotechnology companies, and the pharmaceutical industry to investigate the range of possible treatments for COVID-19 and vaccines to prevent infection from SARS-CoV-2 [1]. Current approaches are drawing on previous studies on severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome (MERS-CoV) [1]. For example, studies have shown that SARS-CoV and SARS-CoV-2 have structural similarities within their respective receptor-binding domains (RBDs) of the S1 spike protein subunit that mediate strong multi-point binding to the extracellular globular domain of angiotensin-converting enzyme-2 (ACE2), which may involve neurological expression [2–9]. Within the lung, widespread expression of ACE2 by alveolar epithelia and capillary cells facilitates viral infection via internalization and replication, leading to severe respiratory disease [2,3]. Recent evidence of co-morbid neurological sequelae of SARS-CoV-2 infection has been reported in the presence or absence of severe respiratory disease where patients have presented with symptoms of nausea, vomiting, anosmia, loss of taste, impaired consciousness, agitation and confusion, corticospinal tract signs, and cerebrovascular diseases, including encephalopathy [5–7].\nAs discussed below, a significant body of empirical studies has demonstrated that the destructive neurological effects of rabies virus (RABV) infections are mediated by CNS transport of the virus tightly bound to the nicotinic acetylcholine receptor (nAChR). It has also been recently hypothesized that a similar mechanism may exist to explain the multiple neurological effects of SARS-CoV-2 via binding to peripheral nAChRs followed by orthograde or retrograde transport into the CNS [10,11]. Potential portals for transport of SARS-CoV-2/nAChR complexes into the CNS include the olfactory nerve and primary olfactory neurons [9,12], and/or peripheral trigeminal sensory terminal structures located within the olfactory epithelium [13,14]. Further studies are required to fully test the hypothesis that the nAChR receptor represents an obligate biochemical chaperone or effector protein responsible for transport of infective SARS-CoV-2 particles into discrete CNS areas. As a corollary, pharmacological targeting of SARS-CoV-2/nAChR complexes may represent a novel vehicle for prevention and control of neurological comorbidities of COVID-19 infection [10]. There is the potential for new clinical trials to investigate nicotine as a means of blocking SARS-CoV-2-nAChR binding to prevent or treat COVID-19 (https://www.theguardian.com/world/2020/apr/22/french-study-suggests-smokers-at-lower-risk-of-getting-coronavirus). As such, we present a critical discussion that integrates lessons learned from prior RABV research and vaccine development into a working model of a SARS-CoV-2 vaccine that selectively targets and neutralizes CNS penetration of a tightly bound viral nAChR complex."}

LitCovid-PD-HP

{"project":"LitCovid-PD-HP","denotations":[{"id":"T3","span":{"begin":1645,"end":1661},"obj":"Phenotype"},{"id":"T4","span":{"begin":1663,"end":1670},"obj":"Phenotype"},{"id":"T5","span":{"begin":1672,"end":1685},"obj":"Phenotype"},{"id":"T6","span":{"begin":1711,"end":1720},"obj":"Phenotype"},{"id":"T7","span":{"begin":1803,"end":1817},"obj":"Phenotype"}],"attributes":[{"id":"A3","pred":"hp_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/HP_0002017"},{"id":"A4","pred":"hp_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/HP_0000458"},{"id":"A5","pred":"hp_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/HP_0000223"},{"id":"A6","pred":"hp_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/HP_0000713"},{"id":"A7","pred":"hp_id","subj":"T7","obj":"http://purl.obolibrary.org/obo/HP_0001298"}],"text":"Background\nThe emergence of the novel β-coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a global pandemic of coronavirus disease 2019 (COVID-19) [1]. Currently, in mid-May 2020, there are over 4,000,000 confirmed cases of COVID-19 and over 300,000 deaths due to COVID-19 worldwide, according to the COVID-19 Dashboard by the Center for Systems Science and Engineering at Johns Hopkins University (https://coronavirus.jhu.edu/map.html).\nThere is now increasing collaborative activity by governments, academic institutions, biotechnology companies, and the pharmaceutical industry to investigate the range of possible treatments for COVID-19 and vaccines to prevent infection from SARS-CoV-2 [1]. Current approaches are drawing on previous studies on severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome (MERS-CoV) [1]. For example, studies have shown that SARS-CoV and SARS-CoV-2 have structural similarities within their respective receptor-binding domains (RBDs) of the S1 spike protein subunit that mediate strong multi-point binding to the extracellular globular domain of angiotensin-converting enzyme-2 (ACE2), which may involve neurological expression [2–9]. Within the lung, widespread expression of ACE2 by alveolar epithelia and capillary cells facilitates viral infection via internalization and replication, leading to severe respiratory disease [2,3]. Recent evidence of co-morbid neurological sequelae of SARS-CoV-2 infection has been reported in the presence or absence of severe respiratory disease where patients have presented with symptoms of nausea, vomiting, anosmia, loss of taste, impaired consciousness, agitation and confusion, corticospinal tract signs, and cerebrovascular diseases, including encephalopathy [5–7].\nAs discussed below, a significant body of empirical studies has demonstrated that the destructive neurological effects of rabies virus (RABV) infections are mediated by CNS transport of the virus tightly bound to the nicotinic acetylcholine receptor (nAChR). It has also been recently hypothesized that a similar mechanism may exist to explain the multiple neurological effects of SARS-CoV-2 via binding to peripheral nAChRs followed by orthograde or retrograde transport into the CNS [10,11]. Potential portals for transport of SARS-CoV-2/nAChR complexes into the CNS include the olfactory nerve and primary olfactory neurons [9,12], and/or peripheral trigeminal sensory terminal structures located within the olfactory epithelium [13,14]. Further studies are required to fully test the hypothesis that the nAChR receptor represents an obligate biochemical chaperone or effector protein responsible for transport of infective SARS-CoV-2 particles into discrete CNS areas. As a corollary, pharmacological targeting of SARS-CoV-2/nAChR complexes may represent a novel vehicle for prevention and control of neurological comorbidities of COVID-19 infection [10]. There is the potential for new clinical trials to investigate nicotine as a means of blocking SARS-CoV-2-nAChR binding to prevent or treat COVID-19 (https://www.theguardian.com/world/2020/apr/22/french-study-suggests-smokers-at-lower-risk-of-getting-coronavirus). As such, we present a critical discussion that integrates lessons learned from prior RABV research and vaccine development into a working model of a SARS-CoV-2 vaccine that selectively targets and neutralizes CNS penetration of a tightly bound viral nAChR complex."}

2_test

{"project":"2_test","denotations":[{"id":"32463026-32105090-69142622","span":{"begin":189,"end":190},"obj":"32105090"},{"id":"32463026-32105090-69142623","span":{"begin":734,"end":735},"obj":"32105090"},{"id":"32463026-32105090-69142624","span":{"begin":898,"end":899},"obj":"32105090"},{"id":"32463026-32155444-69142625","span":{"begin":1243,"end":1244},"obj":"32155444"},{"id":"32463026-32125455-69142625","span":{"begin":1243,"end":1244},"obj":"32125455"},{"id":"32463026-32007145-69142625","span":{"begin":1243,"end":1244},"obj":"32007145"},{"id":"32463026-32283006-69142625","span":{"begin":1243,"end":1244},"obj":"32283006"},{"id":"32463026-32155444-69142626","span":{"begin":1442,"end":1443},"obj":"32155444"},{"id":"32463026-32125455-69142627","span":{"begin":1444,"end":1445},"obj":"32125455"},{"id":"32463026-32283006-69142628","span":{"begin":2453,"end":2454},"obj":"32283006"},{"id":"32463026-15210938-69142629","span":{"begin":2455,"end":2457},"obj":"15210938"},{"id":"32463026-10667995-69142630","span":{"begin":2558,"end":2560},"obj":"10667995"},{"id":"32463026-9853116-69142631","span":{"begin":2561,"end":2563},"obj":"9853116"}],"text":"Background\nThe emergence of the novel β-coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a global pandemic of coronavirus disease 2019 (COVID-19) [1]. Currently, in mid-May 2020, there are over 4,000,000 confirmed cases of COVID-19 and over 300,000 deaths due to COVID-19 worldwide, according to the COVID-19 Dashboard by the Center for Systems Science and Engineering at Johns Hopkins University (https://coronavirus.jhu.edu/map.html).\nThere is now increasing collaborative activity by governments, academic institutions, biotechnology companies, and the pharmaceutical industry to investigate the range of possible treatments for COVID-19 and vaccines to prevent infection from SARS-CoV-2 [1]. Current approaches are drawing on previous studies on severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome (MERS-CoV) [1]. For example, studies have shown that SARS-CoV and SARS-CoV-2 have structural similarities within their respective receptor-binding domains (RBDs) of the S1 spike protein subunit that mediate strong multi-point binding to the extracellular globular domain of angiotensin-converting enzyme-2 (ACE2), which may involve neurological expression [2–9]. Within the lung, widespread expression of ACE2 by alveolar epithelia and capillary cells facilitates viral infection via internalization and replication, leading to severe respiratory disease [2,3]. Recent evidence of co-morbid neurological sequelae of SARS-CoV-2 infection has been reported in the presence or absence of severe respiratory disease where patients have presented with symptoms of nausea, vomiting, anosmia, loss of taste, impaired consciousness, agitation and confusion, corticospinal tract signs, and cerebrovascular diseases, including encephalopathy [5–7].\nAs discussed below, a significant body of empirical studies has demonstrated that the destructive neurological effects of rabies virus (RABV) infections are mediated by CNS transport of the virus tightly bound to the nicotinic acetylcholine receptor (nAChR). It has also been recently hypothesized that a similar mechanism may exist to explain the multiple neurological effects of SARS-CoV-2 via binding to peripheral nAChRs followed by orthograde or retrograde transport into the CNS [10,11]. Potential portals for transport of SARS-CoV-2/nAChR complexes into the CNS include the olfactory nerve and primary olfactory neurons [9,12], and/or peripheral trigeminal sensory terminal structures located within the olfactory epithelium [13,14]. Further studies are required to fully test the hypothesis that the nAChR receptor represents an obligate biochemical chaperone or effector protein responsible for transport of infective SARS-CoV-2 particles into discrete CNS areas. As a corollary, pharmacological targeting of SARS-CoV-2/nAChR complexes may represent a novel vehicle for prevention and control of neurological comorbidities of COVID-19 infection [10]. There is the potential for new clinical trials to investigate nicotine as a means of blocking SARS-CoV-2-nAChR binding to prevent or treat COVID-19 (https://www.theguardian.com/world/2020/apr/22/french-study-suggests-smokers-at-lower-risk-of-getting-coronavirus). As such, we present a critical discussion that integrates lessons learned from prior RABV research and vaccine development into a working model of a SARS-CoV-2 vaccine that selectively targets and neutralizes CNS penetration of a tightly bound viral nAChR complex."}

PMC:7278327 / 1562-5075 JSONTXT

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PMC:7278327 / 1562-5075 JSON TXT