A new method has been developed to identify specific molecular targets that may be used to disrupt the life cycle of the SARS-CoV-2 virus. Simulations and protein engineering efforts could help researchers to identify compounds that would interfere with the spike protein’s function, which would stop the virus from entering the cell. SARS-CoV-2’s genome is passed on to other cells by its spike protein, which transmits it by sticking to host cells. The spike protein is composed of three different kinds of components.
“Most of the current SARS-CoV-2 treatments and vaccines have focused on the ACE2 recognition step of virus invasion, but an alternative strategy is to target the structural change that allows the virus to fuse with the human host cell. But probing these intermediate, transient structures experimentally is extremely difficult, and so we used a computer simulation sufficiently simplified to investigate this large system, but that maintains sufficient physical details to capture the dynamics of the S2 subunit as it transitions between pre-fusion and post-fusion shapes,” explained study co-author José N. Onuchic, Professor of Physics at Rice University, Houston.
Glycans are sugar molecules that attach to proteins; they help to maintain stability in membrane fusion. The scientists verified stability in their simulations of glycans on the spike protein by determining the number, type, and position of glycans. Researchers simulated how glycans interact with spike proteins and found that the interaction caused spike proteins to pause before interacting with the host cell’s membrane. This gave time for fusion peptides to attach themselves to the membrane. It has been discovered that in the absence of sugars, these particles are no longer infectious. The study revealed how sugars control infectivity and provided a foundation for investigating factors that influence this pathogen’s dynamics.