Landmark New Publication: the Forgotten Biochemistry 101 of COVID-19
Legacy coronavirus biochemistry was overlooked that governs spike protein toxicity, key morbidities, risk factors and therapeutic responses
SALT LAKE CITY, April 22, 2024 /PRNewswire/ -- TrialSite News features a paper published today in Viruses (Basel), authored byan international team of researchers, including two fellows of their nations' academies of sciences (Colleen Aldous, senior author Wendy Hoy) and others who participated in Nobel prize-honored research (Thomas Borody, Morimasa Yagisawa). The publication reveals how coronavirus biochemistry well-established over past decades governs the morbidities of COVID-19, risk factors and therapeutic approaches.
The glycan monomer sialic acid, ubiquitous on eukaryotic cell surfaces, serves as the initial attachment point to host cells for the COVID19 virusSARSCoV2as well as for other coronaviruses. The virus can then slide over to ACE2 for cell entry. SARSCoV2 spike protein attaches particularly tightly to the dense sialic acid coatings on the trillions of red blood cells (RBCs), platelets and endothelial cells in the human adult. These interlaced attachments trigger the RBC aggregation, microvascular occlusion and vascular damage underlying the oxygen deficits, blood clotting and related morbidities of severe COVID19.
In the genetics-centric research environment of recent decades, however, most COVID19 research ignored this older, well-established biochemistry, focusing instead on SARSCoV2 replication and its replication receptor, ACE2. Yet the typical human cell is coated with at most a few hundred ACE2 molecules vs. millions of virally-binding sialic acid molecules. This misdirected focus led to oversights of significant consequence, as detailed in the Viruses paper.
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.
Substantiation of the importance of thisglycan biochemistry for COVID19:
- RBC aggregation as experimentally induced in several animal species using an injected polysaccharide caused most of the same morbidities of severe COVID?19.
- Three major risk factors for COVID19 mortalityolder age, diabetes and obesityare each associated with significantly increasedRBC aggregation and microvascular occlusion.
- Three generic drugs that gleaned most interest as COVID19 therapeutics each reduce blood cell aggregationonedisaggregated virally induced RBC clumps in vitro within 30 minutes.
- For mammalian species, clinical susceptibility to COVID19 correlates toRBC aggregability (p=0.03).
- The two humanbetacoronaviruses that express a sialic acid-cleaving enzyme, hemagglutinin esterase, are benign, while the other threeSARS, SARSCoV2, and MERSare virulent.
As detailed in the newly published paper, thisglycan biochemistry is also key to disentangling controversies that have arisen over the efficacy of certain generic COVID19 treatment agents, one of which competitively binds to several sites on SARSCoV2 spike protein, and the safety of spike protein-based COVID19 vaccines.
The paper further considers how an appreciation of the related active physiological role of RBCs, the most abundant cells in the human body, can elucidate the microvascular underpinnings of other health conditions, including cardiovascular disease, and therapeutic opportunities to address them.
Contact: David Scheim, corresponding author dscheim@alum.mit.edu
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SOURCE TrialSite News

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