# RRM Prediction of Erythrocyte Band3 Protein as Alternative Receptor for SARS-CoV-2 Virus
## 3 Results  
Our focus here is to find out how SARS-CoV-2 infects different cell types. The main entry point into cells for some coronaviruses, including HCoV-NL63, SARS-CoV (the virus that causes SARS) [19] and SARS-CoV-2 (the virus that causes COVID-19) [20] is angiotensin-converting enzyme 2 (ACE2), which is attached to the outer surface of the cell membranes of cells in the lungs, arteries, heart, kidney and intestines. More specifically, the binding of the spike S1 protein of SARS-CoV and SARS-CoV-2 to the enzymatic domain of ACE2 on the surface of cells results in endocytosis and the translocation of both the virus and the enzyme into endosomes located within cells [21]. We have utilized the RRM model to analyze the interaction between spike S1 protein and the ACE2 receptor to find the RRM frequency characterizing this interaction. To achieve this, we have compared, using the RRM cross-spectra function, ACE2 receptors and S1 spike proteins from coronaviruses that are interacting with the ACE2 receptor, as listed in the Section 2.2. The prominent common characteristic frequency appears to be at an RRM frequency of 0.3145, as presented in Figure 1.  
According to RRM principles, this frequency is characterizing the interaction between S1 spikes and ACE2 receptors. To confirm that the S1 spike from SARS-CoV-2 can interact with the human ACE2 receptor, we calculated phases for those two proteins at an RRM characteristic frequency of 0.3145 to find out if they are opposite, as required by RRM for successful interaction. The phase for S1 spike was found to be at -1.74 rad, while the phase for human ACE2 receptor was found to be at +2.26 rad, indicating that their phase difference is 2.28 rad, which is empirically shown to be opposite enough to enable successful interaction [3; 4; 5; 6]. To explain why severe cases of SARS-CoV-2 virus infection are causing extremely and dangerously low levels of oxygen in the blood in the absence of a lung infection, and where the patient's ability to breathe is not proportionally affected, we propose that there may be another target receptor for SARS-CoV-2. Thus, we propose that SARS-CoV-2 can not only infect cells through the ACE2 receptor, but also through some other pathway. As oxygen is captured and transported by the red blood cells, it is logical to investigate the possibility that red blood cells are also infected by SARS-CoV-2, causing the capture of oxygen to be disturbed and explaining the disproportionally low level of oxygen in the blood (hypoxia) in severely ill patients. Red blood cells do not have ACE2 receptors on their surface and thus we propose that there might be another pathway on the surface of red blood cells that can interact with S1 spike proteins. One such possible pathway is through the interaction with the red blood cell (RBC) Band3 surface protein, which is a ubiquitous membrane transport protein found in the plasma membrane. It is the major integral transmembrane protein of the erythrocyte plasma membrane, comprising 25% of the total membrane proteins. Interestingly, it has been hypothesized that the main route of RBC invasion by merozoites from malaria parasites occurs through the RBC Band3-dependent pathway [10,22]. When we compared coronavirus S1 spike proteins to RBC Band3 surface proteins, using the RRM cross-spectra function, strikingly, we found the prominent common RRM characteristic frequency of 0.3145 was exactly the same as the frequency for the interaction between S1 spikes and ACE2 receptors, as presented in Figure 2.  
This indicates not only the possibility that S1 spikes interact with RBC Band3 proteins, but also that this interaction uses the same mechanism as the interaction between S1 spikes and ACE2 receptors. If the interaction between S1 spikes and RBC Band3 surface proteins is possible, then it means that red blood cells can be infected by SARS-CoV-2 and thus the capture of oxygen could be affected, causing severely low levels of oxygen in the blood (hypoxia).