SARS-CoV-2 directly affects heme synthesis ??

Well — these GEITP pages would like to “move on” from the mechanisms of SARS-CoV-2 infection — but the intriguing hypotheses continue to appear in our current literature. THIS article [attached; from Sichuan and Yibin Universities], pushed on me last evening by a fellow GEITP-er, is at least worth examining more closely. ☹

SARS-CoV-2 is a positive-strand single-stranded RNA [(+)-ssRNA] virus that exhibits high homology to bat coronavirus and is the cause of our current COVID-19 pandemic. Authors [see attached article] used “conserved domain analysis, homology modeling, and molecular docking” (structural chemistry analysis) to “compare biological roles of certain proteins of the novel virus.” Their results showed the open-reading frame-8 (ORF8) protein, and surface glycoprotein, “could both bind to porphyrin.” Concomitantly, the orf1ab, ORF10, and ORF3a proteins “could coordinate an attack on the heme of the 1-beta chain of hemoglobin — to dissociate iron, which is needed to form the porphyrin.”

“This attack would then cause increasingly less less functional hemoglobin [required to carry oxygen (O2) to the body and carbon dioxide (CO2) back through the venous system to the lungs for exhalation).” Clinically, lung epithelial cells do display severe inflammatory changes — which present like high-altitude pulmonary edema (HAPE), i.e. oxygen deprivation. Authors state that “dissociation of iron from hemoglobin would also interfere with other pathways in which heme is needed for various functions of other molecules in the body.”

According to this analysis, authors suggest that chloroquine “could prevent the orf1ab, ORF3a, and ORF10 proteins from attacking the heme” — which might reflect the clinical response to the drug of effectively relieving symptoms of dyspnea (respiratory distress). Authors also suggest that favipiravir “could inhibit the envelope protein and ORF7a protein from binding to porphyrin.” Authors do warn that their “paper is only for academic discussion,” and proof of their hypotheses “would require confirmation by further studies.” In the humble opinion of these GEITP pages (having had first-hand experience during a MS degree in biophysics in which many artifacts in vitro were never relevant to clinical medicine) — this (structural biology in silico) paper represents a lot of hand-waving and smoke-and-mirrors and has little to do with reality. ☹


ChemRxiv. Preprint.


Thank you, Andy, for your input from a heme biosynthesis expert. 😊
As far as elevated hemoglobin levels in these ARDS patients, Alvaro, the first thing — that comes to mind as a clinician — is dehydration (loss of fluids from the intravascular space, which leads to increased concentration of red cells and other components), which of course is seen with fever, and occurs more commonly among young children and geriatric patients with underlying medical conditions. ☹


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