COVID-19:Attacks the 1-Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism

13 July 2020, Version 9
This content is a preprint and has not undergone peer review at the time of posting.


The novel coronavirus pneumonia (COVID-19) is an infectious acute respiratory caused by the novel coronavirus. The virus is the positive-strand RNA one with high homology to bat coronavirus. The pathogenic mechanism of the new coronavirus is still unclear, which is a significant obstacle to the development of drugs and patients' rescue. In this study, conserved domain analysis, homology modeling, and molecular docking were made to compare the biological roles of specific proteins belonging to the novel coronavirus. The conserved domain analysis showed envelope protein (E), nucleocapsid phosphoprotein (N) and ORF3a had heme linked sites, which Arg134 of ORF3a, Cys44 of E, Ile304 of N were the heme-iron linked site, respectively. ORF3a also possessed the conserved domains of human cytochrome C reductases and bacterial EFeB protein. These three domains were highly overlapping so that ORF3a could dissociate the iron of heme to form porphyrin. Heme linked sites of E protein may be relevant to the high infectivity, and the role of heme linked sites of N protein may be related to the virus replication. The docking results showed that orf1ab, ORF10, and ORF3a proteins coordinated to attack the 1-beta chain of hemoglobin, and some structural and non-structural viral proteins could bind porphyrin. Deoxyhemoglobin was more vulnerable to virus attacks than oxidized hemoglobin. But ORF3a was specific and would not attack blue blood protein, normal cytochrome C, and peroxidase. As for the attack, it would cause increasingly less hemoglobin that could carry oxygen and carbon dioxide, thus producing symptoms of respiratory distress and coagulation reaction, damaging many organs and tissues. The mechanism also interfered with the normal heme anabolic pathway of the human body, expecting to cause human diseases. Based on the small molecule drug library, drugbank, we searched for drugs bound to viral proteins by molecular docking. The results showed that some anticancer drugs could attach to the heme-iron linked site of ORF3a and N. Remdesivir was relatively more obvious than Hydroxychloroquine and Chloroquine in terms of the binding capacity of ORF3a, but the combined role of three drugs to ORF3a was lower. Unfortunately, no drug could bind to the heme-iron linked site of E. Besides, these higher binding energies may prevent all screened drugs from binding firmly to viral proteins. Since there were no clinical data, so inhibitory effects on ORF3a and N were still unclear. This theory is only for academic discussion and needed to be verified by other experiments. Please consult a qualified doctor for treatment details. Due to the toxicity and side effects of drugs, do not use medicines yourself. We expect these discoveries to bring more ideas to people to relieve patients' symptoms and save more lives.


novel coronavirus
fluorescence resonance energy transfer
Respiratory distress
Ground-glass-Like Lung
E2 glycoprotein
Ancient virus
Cytokine Storm
ORF 3a protein


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