Health
New insights into coronavirus spike proteins may stimulate vaccine development
Many studies looking for solutions to the COVID-19 pandemic have focused on spike proteins. Spike proteins play an important role in the ability of viruses to bind and infect healthy cells. Instead, a team led by scientists at the University of California, San Diego (UCSD) focused on glycans that link sugar chain molecules that protect spike proteins.
In a new study published in the journal ACS Central ScienceThe team revealed the important role of N-glycans at two sites of SARS-CoV-2 (the coronavirus behind COVID-19) in target cell recognition and promotion of infection. They suggest that the findings offer a new strategy for vaccine development.
The sugar chains that surround viral proteins are known to be important for the prosperity of the virus. For example, a thick glycan shield around HIV-1 has been shown to allow the virus to evade the immune system. However, unlike HIV-1, which contains viral proteins covered with a non-immunogenic glycan shield, SARS-CoV-2 appears to have spike proteins covered with different glycan patterns. The UCSD-led team believed that certain glycans could be the key to infection and could be vaccine targets.
Researchers have constructed a full-length model of the SARS-CoV-2 spike protein with a sugar coating. Computer simulation presented detailed snapshots of all atoms of the spiked glycoprotein.
The SARS-CoV-2 spike protein enters the host cell by immobilizing its receptor binding domain (RBD) on the ACE2 protein on the cell surface. In this study, UCSD researchers found that N-type glycans linked to spike proteins at sites N165 and N234 help stabilize the shape of RBD against subsequent infections. The team reported that introducing mutations into N165 and N234 to remove these glycans significantly reduced binding to ACE2.
Relation: Beyond the COVID-19 spike protein, look to the next wave of vaccines
In addition, UCSD researchers have shown that the stems of spike proteins that secure the spherical head containing RBD to the surface of the virus are densely covered with glycans. This makes it difficult to target large molecules such as antibodies. By comparison, the head appears unshielded, indicating that it could be an easier target, the team suggested.
While most COVID-19 vaccine development has focused on inducing neutralizing antibodies that target spike proteins, there is growing interest in finding solutions elsewhere to kill the virus. Inducing an immune response in T cells is one such idea. For example, a team led by TScan Therapeutics studied memory CD8 + T cells in patients who recovered from COVID-19 and found that most of the T cell-targeted sites were outside the spike protein.
The researchers said the UCSD-led team hopes to uncover the important roles of N165 and N234 in SARS-CoV-2 infection, opening up new opportunities in vaccine development.
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