Investigating the Structure and Function of SARS-CoV-2 Spike Protein by Molecular Docking

It has been more than two years since the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China. The SARS-CoV-2 has created an unprecedented pandemic (COVID-19) in the modern era and challenged all the scientific, economic, and social structures of the world. Extensive worldwide research has been conducted to study the structure and function of the SARS-CoV-2 spike protein since the beginning of the pandemic. The role and importance of spike protein in the introduction of SARS-CoV-2 into human cells has been proven. Among the important and effective factors in controlling the Covid-19 pandemic is understanding the structural changes of spike protein in different variants of the virus and the effectiveness of drugs and vaccines against new SARS-CoV-2 variants. Due to the great importance of spike protein SARS-CoV-2, it was tried to study its structure and interaction with cellular receptors using bioinformatics tools in this study. Furthermore, the effects of different SARS-CoV-2 variants on existing drugs and vaccines were reviewed.

The bioinformatics methods and molecular docking was used to study the binding function of spike protein to its various cellular receptors in the human body. HDOCK web server was used to perform the molecular docking process and in the next step, the PDBsum web server was used for post-docking checks and to ensure the accuracy of the obtained data. PyMOL software was also used to study and visualize replacement and deletion mutations in the spike protein.

Extensive mutations in the spike protein in the omicron variant indicate a redesign in the spike protein. These massive mutations cause extensive changes in the structure and function of the spike protein. The data obtained from molecular docking and comparing the energy level (docking score) of spike protein binding of different variants of the virus with different cellular receptors indicate a high tendency of the spike protein to bind, with lower energy levels and more stable, to KREMEN1 receptor than the main ACE2 receptor.  The level of spike protein binding energy levels of different virus variants was almost similar to other receptors (except the KREMEN1 receptor) or slightly different from the spike protein binding energy levels with the main ACE2 receptor.

There is not much difference in the tendency of spike protein binding of emerging and important variants of the virus (main, alpha, delta, and omicron) to ACE2 receptor, but the tendency to bind to KREMEN1 receptor is increasing and has reached its peak in the delta variant. The energy level of the spike protein binding to the KREMEN1 receptor is significantly negative compared to other receptors, indicating greater binding and stability. Also, considering the level of energy received from the HDOCK web server, it can be concluded that although the ACE2 receptor is the main receptor for the spike protein, other receptors can still bind to the spike protein with good stability. Based on the available information, so far there have been no reports of docking between spike protein and other non-main spike protein receptors (AXL, ASGR1, KREMEN1). Therefore, more comprehensive research is needed to confirm or refute these findings.