# RRM Prediction of Erythrocyte Band3 Protein as Alternative Receptor for SARS-CoV-2 Virus
## 4 Discussion  
SARS-CoV-2, as a completely new virus that has caused a worldwide pandemic, is very infectious, but 80-90% of infected individuals have only mild or no symptoms. However, a small percentage of infected individuals experience severe symptoms, mostly through infected lungs, difficulties with their breathing and, more intriguingly, seriously low levels of oxygen in their blood. Here, we focused on an anomaly of severe cases of COVID-19 infection, where the function of infected lungs is not severely damaged, but the oxygen level in the blood becomes dangerously low. We propose that this anomaly is due to the possibility that SARS-CoV-2 virus not only infects lung cells, but can also pass through the alveoli membrane to infect red blood cells and consequently cause an unexpected  
Figure 3: Phase circles at frequency of 0.3145 for S1 spike from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with phase of \(-1.7\)rad in green, for human ACE2 receptor with phase of \(+2.26\)rad in blue and for human RBC Band3 surface protein with phase of \(+1.91\)rad in red. It can be easily observed that both receptor phases are almost opposite to the S1 spike phase, supporting the RRM approach that proteins and protein receptors should have opposite phases at frequencies characterizing their recognition and interaction. Figure 2: RRM cross-spectrum for interaction between S1 spike proteins and red blood cell (RBC) Band3 surface proteins with common RRM characteristic frequency of 0.3145.  
disproportional drop in the oxygen levels in the blood. To find out if such red blood cell infection is possible, we utilized our own biophysical Resonant Recognition Model (RRM), which is able to analyze protein interactions with their targets, particularly receptors, by identifying matching periodicities (frequencies) in the distribution of free electron energies along the interacting proteins, characterizing their mutual recognition. Firstly, we analyzed the interaction between the S1 spike protein and the ACE2 receptor, as known receptors of SARS-CoV-2, and we identified the common RRM characteristic frequency of 0.3145. Secondly, we analyzed the interaction between S1 spike proteins and possible proteins on the surface of red blood cells. Strikingly, we found that the RBC Band3 surface proteins have the same RRM characteristics as ACE2 receptors when compared with S1 spike proteins from coronaviruses. In addition, it has been shown that the human RBC Band3 surface protein and the human ACE2 receptor have similar phases at this characteristic RRM frequency of 0.3145, both approximately opposite to the phase at the same RRM frequency for the S1 spike from SARS-CoV-2 (Figure 3). Thus, we propose that the RBC Band3 surface protein can also interact with the S1 spike protein from coronaviruses and therefore could be an entry point of SARS-CoV-2 into the red blood cells (erythrocytes). The hypothesis that the RBC Band3 surface protein can interact with SARS-CoV-2 could be of huge importance, as RBC Band3 protein integrity is mandatory for RBC physiology and, if disturbed, it can severely hamper RBC function, i.e., oxygen transport [23]. If the RBC oxygen transport function is disturbed by an interaction between the S1 fragment of SARS-CoV-2 and the RBC Band3 surface protein, it can cause severe hypoxia, as detected in severe cases of COVID-19. Thus, we propose that hypoxia in severe cases of COVID-19 is caused by SARS-CoV-2 interacting with the RBC Band3 surface protein and hampering RBC oxygen transport function. Our future research will be directed towards the use of the RRM protein design capability to design and test peptides that are able to interfere with and counteract interactions between the S1 fragment of SARS-CoV-2 and both ACE2 receptors and RBC Band3 surface proteins, using the identified RRM frequencies and phases. It is interesting to note that the RBC Band3 protein has been already found to be an entry point for the malarial parasite agents' merozoites from plasmodium falciparum into red blood cells [24].