Transition Structures Between Unbound and Bound SARS-CoV-2 Spike Protein to Human ACE2: Potential Targets for Drug Design

The recent outbreak of COVID-19 caused by SARS-CoV-2 led to a race in finding a cure. Different drug targets were recognized, but in most cases the main target has been identified in the virus spike protein because it is crucial for the virus to gain entry into human cells. The virus spike protein undergoes large dynamic changes in order to bind to the entry point in human cells, which is a surface protein known as Angiotensin-Converting Enzyme 2 (ACE2). The spike – ACE2 interaction represents the major target for vaccines and antiviral drugs. Incidentally, all intermediate structures in the folding pathways could become potential drug targets. This study reports the simulation of the transition pathway of the spike protein and includes its animation that can help also non-experts to visually understand how the infection starts. The simulation of the spike protein's transition pathway has been done by using the NMSim software, which makes use of a three-step protocol including Coarse Grain, Normal Mode Analysis, and Elastic Network Model methods, providing realistic intermediates at a reasonable simulation time.