![]() ![]() The open position is required for ACE2 binding. The S1 subunit RBD can be in a closed or an opened conformation. S1 is responsible for binding to the ACE2 receptor and S2 is responsible for host membrane fusion ( 4, 9– 12). The S protein is a trimeric class I fusion protein ( Figure 1) with two functional subunits: S1 and S2. The SARS-CoV and SARS-CoV-2 S proteins are highly similar and their structure together with their glycosylation sites have been partly established ( 4– 8). ACE2 as the main functional receptor was already identified for the SARS-CoV in 2003 when it was also established that the binding site (Receptor Binding Domain, RBD) was localized between amino acid residues 303 and 537 of the virus S protein ( 3, 4). This process induces a conformational change of these viral ligands resulting in fusion with the host cell membrane delivering the virus genome to the cytoplasm ( 2). The majority of enveloped viruses bind to host cell surface receptors via their surface glycoproteins. The main site of the viral entry of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is through lung epithelial cells involving interactions between the Angiotensin Converting Enzyme 2 (ACE2) and the Spike glycoprotein (S protein) ( 1). Interestingly, however, the results suggest that the most tightly-bound SP-A binding site is localized to the S2 chain, in the fusion region of the SARS-CoV-2 S protein, that is responsible for cell entry Based on these findings we speculate that SP-A may not directly compete with ACE2 for the binding site on the S protein, but interferes with viral entry to the cell by hindering necessary conformational changes or the fusion process. Our data indicate that SP-A could ligate the S protein with a similar affinity to the ACE2-Spike binding. The relative binding affinity of potential interactions between the pruned protein chain residues of SP-A and SARS-CoV-2 S proteins was assessed by the ZDOCK program. ![]() QAOA-MaxCut was compared with GROMACS with T-REMD using AMBER, OPLS, and CHARMM force fields to determine the differences in preparing a protein structure docking, as well as with Goemans-Williamson, the best classical algorithm for MaxCut. We confirmed that the remaining residues contained all the potential binding sites in the molecules by the Universal Protein Resource (UniProt) database. In this, the angles between every neighboring three atoms were Fourier-transformed into microwave frequencies and sent to a quantum chip that identified the chemically irrelevant atoms to eliminate based on their chemical topology. This graph pruning technique determines the best binding sites between amino acid chains by utilizing the Quantum Approximate Optimization Algorithm (QAOA)-based MaxCut (QAOA-MaxCut) program on a Near Intermediate Scale Quantum (NISQ) device. To study this hypothesis, we used a hybrid quantum and classical in silico modeling technique that utilized protein graph pruning. We hypothesized that SP-A binds to the SARS-CoV-2 S protein and this binding interferes with ACE2 ligation. SARS-CoV-2 enters airway epithelial cells by ligating the Angiotensin Converting Enzyme 2 (ACE2) receptor on the cell surface using its Spike glycoprotein (S protein). It binds to the cell membrane of immune cells and opsonizes infectious agents such as bacteria, fungi, and viruses through glycoprotein binding. The pulmonary surfactant protein A (SP-A) is a constitutively expressed immune-protective collagenous lectin (collectin) in the lung.
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