By Mariia Ovodiuk
A novel study by Chinese investigators suggests that SARS-CoV-2 may have the ability to dissociate iron from the porphyrin and bond with porphyrin itself. The alterations in the hemoglobin function, investigators claim, can be the cause of the additional lung damage and respiratory distress.
Image/NIAID-RML
Moreover, the ubiquitous nature of the porphyrin in the host organism and its ability to penetrate cell membranes is considered as a factor which explains the high rates of COVID-19 transmission.
The study design included computational modeling (homology modeling, molecular and protein docking). Investigators evaluated the bonding energy between the porphyrin and different viral proteins. Then, the ability of the virus to disrupt the iron-porphyrine bond was estimated by comparison of the concerved domains of both heme oxidase (the host enzyme which oxidizes heme and dissociates iron ion) and viral proteins. It was found that orflab, ORF10 and ORF3a proteins can dissociate iron from the 1-beta chain of hemoglobin and ORF8 and surface glycoprotein could bind to porphyrin.
The study also evaluated potential chloroquine mechanisms of action, i.e. chloroquine bonds with different viral proteins. The target was to find the bonding energy of viral protein and chloroquine which will be higher than that with po
rphyrin. The results showed that the binding energy of orflab protein and the chloroquine was 8-fold of the binding energy between the orflab an the porphyrin.
Other results were much less satisfactory, so the chloroquine efficacy may be limited in vivo.
The possible effect of the novel antiviral drug Favipiravir was estimated. It has been shown that the bonding energy between Favipiravir and envelope protein, ORF7a and orflab is much higher than that with porphyrin. However, investigators note, the binding energy of orflab and Favipiravir is lower than with chloroquine, which suggests that Favipiravir may be less effective in reducing respiratory distress.
Despite the results obtained, investigators insist that data of the study has its limitations due to computational modeling study design and should be confirmed by other laboratories.
Mariia Ovodiuk is an infectious disease specialist from Kyiv, Ukraine, and a member of the European AIDS Clinical Society. Her scientific interests include: infectious diseases pathophysiology, epigenetics and molecular epidemiology.
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Coronavirus is as man made evil unleashed on the human race to eliminate and control the world population.
If that was true, they would have made it (a) deadlier and (b) lethal to all age ranges. Your idea holds little merit.
It’s not legos; what is created is not always what is desired, but highly disruptive. This virus is too precise, too suitable for human interaction. Your rebuttal holds little merit.
Bravo, now what?
You should ask for the manager.
This paper is based purely on theoretical data modeling that is notoriously inaccurate. The authors fail to provide corroborating experimental data. They fail to propose a mechanism or pathway by which the viral proteins are exposed to the erythrocyte intracellular environment.
The paper also states that in vitro interaction between the S protein and ACE2 is “weak in vitro”. And from that point they hand wave a vague model of “ancient infection mechanisms”.
A. In vitro interaction assays do not correlate with in vivo affinities. I could be considered an expert on this particular point because this was a huge part of my research – in vitro protein interaction assays.
So it’s entirely possible that in vivo affinity is strong enough to align with observations that ACE2 is the entry receptor.
B. It’s equally possible that there is a 1. Coreceptor we have yet to identify, 2. isoform variant, or 3. A post-translational modification such as phosphorylation or glycosylation.
Until there is evidence of erythrocyte infection or some downstream impact on their lifespan, the ideas related to hemoglobin are not reasonable.
So what do you think covid would do to someone that has porphyria and has a large excess of porhyrins in their organs?