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.
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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