Back to the Basics of SARS-CoV-2 Biochemistry: Microvascular Occlusive Glycan Bindings Govern Its Morbidities and Inform Therapeutic Responses
Consistent with the biochemistry of coronaviruses as well established over decades, SARS-CoV-2 makes its initial attachment to host cells through the binding of its spike protein (SP) to sialylated glycans (containing the monosaccharide sialic acid) on the cell surface. The virus can then slide over...
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| Format: | Article |
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MDPI AG
2024
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| Online Access: | https://hdl.handle.net/1721.1/154298 |
| _version_ | 1811083542092840960 |
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| author | Scheim, David E. Parry, Peter I. Rabbolini, David J. Aldous, Colleen Yagisawa, Morimasa Clancy, Robert Borody, Thomas J. Hoy, Wendy E. |
| author_facet | Scheim, David E. Parry, Peter I. Rabbolini, David J. Aldous, Colleen Yagisawa, Morimasa Clancy, Robert Borody, Thomas J. Hoy, Wendy E. |
| author_sort | Scheim, David E. |
| collection | MIT |
| description | Consistent with the biochemistry of coronaviruses as well established over decades, SARS-CoV-2 makes its initial attachment to host cells through the binding of its spike protein (SP) to sialylated glycans (containing the monosaccharide sialic acid) on the cell surface. The virus can then slide over and enter via ACE2. SARS-CoV-2 SP attaches particularly tightly to the trillions of red blood cells (RBCs), platelets and endothelial cells in the human body, each cell very densely coated with sialic acid surface molecules but having no ACE2 or minimal ACE2. These interlaced attachments trigger the blood cell aggregation, microvascular occlusion and vascular damage that underlie the hypoxia, blood clotting and related morbidities of severe COVID-19. Notably, the two human betacoronaviruses that express a sialic acid-cleaving enzyme are benign, while the other three—SARS, SARS-CoV-2 and MERS—are virulent. RBC aggregation experimentally induced in several animal species using an injected polysaccharide caused most of the same morbidities of severe COVID-19. This glycan biochemistry is key to disentangling controversies that have arisen over the efficacy of certain generic COVID-19 treatment agents and the safety of SP-based COVID-19 vaccines. More broadly, disregard for the active physiological role of RBCs yields unreliable or erroneous reporting of pharmacokinetic parameters as routinely obtained for most drugs and other bioactive agents using detection in plasma, with whole-blood levels being up to 30-fold higher. Appreciation of the active role of RBCs can elucidate the microvascular underpinnings of other health conditions, including cardiovascular disease, and therapeutic opportunities to address them. |
| first_indexed | 2024-09-23T12:34:43Z |
| format | Article |
| id | mit-1721.1/154298 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T12:34:43Z |
| publishDate | 2024 |
| publisher | MDPI AG |
| record_format | dspace |
| spelling | mit-1721.1/1542982024-09-09T04:47:14Z Back to the Basics of SARS-CoV-2 Biochemistry: Microvascular Occlusive Glycan Bindings Govern Its Morbidities and Inform Therapeutic Responses Scheim, David E. Parry, Peter I. Rabbolini, David J. Aldous, Colleen Yagisawa, Morimasa Clancy, Robert Borody, Thomas J. Hoy, Wendy E. Consistent with the biochemistry of coronaviruses as well established over decades, SARS-CoV-2 makes its initial attachment to host cells through the binding of its spike protein (SP) to sialylated glycans (containing the monosaccharide sialic acid) on the cell surface. The virus can then slide over and enter via ACE2. SARS-CoV-2 SP attaches particularly tightly to the trillions of red blood cells (RBCs), platelets and endothelial cells in the human body, each cell very densely coated with sialic acid surface molecules but having no ACE2 or minimal ACE2. These interlaced attachments trigger the blood cell aggregation, microvascular occlusion and vascular damage that underlie the hypoxia, blood clotting and related morbidities of severe COVID-19. Notably, the two human betacoronaviruses that express a sialic acid-cleaving enzyme are benign, while the other three—SARS, SARS-CoV-2 and MERS—are virulent. RBC aggregation experimentally induced in several animal species using an injected polysaccharide caused most of the same morbidities of severe COVID-19. This glycan biochemistry is key to disentangling controversies that have arisen over the efficacy of certain generic COVID-19 treatment agents and the safety of SP-based COVID-19 vaccines. More broadly, disregard for the active physiological role of RBCs yields unreliable or erroneous reporting of pharmacokinetic parameters as routinely obtained for most drugs and other bioactive agents using detection in plasma, with whole-blood levels being up to 30-fold higher. Appreciation of the active role of RBCs can elucidate the microvascular underpinnings of other health conditions, including cardiovascular disease, and therapeutic opportunities to address them. 2024-04-26T14:30:45Z 2024-04-26T14:30:45Z 2024-04-22 2024-04-26T13:09:21Z Article http://purl.org/eprint/type/JournalArticle 1999-4915 https://hdl.handle.net/1721.1/154298 Scheim, D.E.; Parry, P.I.; Rabbolini, D.J.; Aldous, C.; Yagisawa, M.; Clancy, R.; Borody, T.J.; Hoy, W.E. Back to the Basics of SARS-CoV-2 Biochemistry: Microvascular Occlusive Glycan Bindings Govern Its Morbidities and Inform Therapeutic Responses. Viruses 2024, 16, 647. PUBLISHER_CC 10.3390/v16040647 Viruses Creative Commons Attribution https://creativecommons.org/licenses/by/4.0/ application/pdf MDPI AG Multidisciplinary Digital Publishing Institute |
| spellingShingle | Scheim, David E. Parry, Peter I. Rabbolini, David J. Aldous, Colleen Yagisawa, Morimasa Clancy, Robert Borody, Thomas J. Hoy, Wendy E. Back to the Basics of SARS-CoV-2 Biochemistry: Microvascular Occlusive Glycan Bindings Govern Its Morbidities and Inform Therapeutic Responses |
| title | Back to the Basics of SARS-CoV-2 Biochemistry: Microvascular Occlusive Glycan Bindings Govern Its Morbidities and Inform Therapeutic Responses |
| title_full | Back to the Basics of SARS-CoV-2 Biochemistry: Microvascular Occlusive Glycan Bindings Govern Its Morbidities and Inform Therapeutic Responses |
| title_fullStr | Back to the Basics of SARS-CoV-2 Biochemistry: Microvascular Occlusive Glycan Bindings Govern Its Morbidities and Inform Therapeutic Responses |
| title_full_unstemmed | Back to the Basics of SARS-CoV-2 Biochemistry: Microvascular Occlusive Glycan Bindings Govern Its Morbidities and Inform Therapeutic Responses |
| title_short | Back to the Basics of SARS-CoV-2 Biochemistry: Microvascular Occlusive Glycan Bindings Govern Its Morbidities and Inform Therapeutic Responses |
| title_sort | back to the basics of sars cov 2 biochemistry microvascular occlusive glycan bindings govern its morbidities and inform therapeutic responses |
| url | https://hdl.handle.net/1721.1/154298 |
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