­Production of a stabilized ectodomain trimer of SARS-CoV-2 spike protein

Background

The COVID-19 pandemic highlighted the exceptional ability of certain viruses to genetically mutate, altering themselves in order evade the immune response of their host. In RNA-viruses such as SARS-CoV-19, a single strand of RNA is responsible for reprogramming host cells to produce the major proteins that constitute the viral particle. Among these viral proteins, the trimeric spike protein (S) is the protein that initiates the attachment of the virus to the host cells by binding to the Angiotensin-converting enzyme 2 (ACE2) receptor.

The host’s immune system neutralizes the viral infection through recognizing virus-specific proteins and producing antibodies against these proteins. In the case of SARS-CoV-19, the S protein is recognized by the immune system and is also the protein used to identify the viral strain for the development of vaccines against the virus. However, due to the high mutability of the viral S protein in SARS-CoV-19, vaccines have proven to be only moderately efficacious.

Technology Overview

Boston Children’s Hospital researchers studied the S protein to advance knowledge of the SARS-CoV-2 entry process and characterized S proteins from Delta, Kappa, and Gamma variants to determine their structures and provide insights into the mechanisms of the heightened transmissibility and enhanced immune evasion of SARS-CoV-2 strains. These discoveries can lead to deeper understanding of the virus’s pathogenicity and have the potential to help pinpoint the most effective approaches for diagnosing, treating, and protecting patients against the virus.

Applications

1. The ability to develop very accurate diagnostic testing for Coronavirus inactions, through increased sensitivity and specificity of the test.
2. Manufacturing more effective vaccines that efficiently target the specific S protein antigen of the delta coronavirus strain.
3. Development of antibody therapies for already infected individuals. These antibodies can provide therapeutic neutralizing treatment to prevent possible further complications, especially in individuals with reduced immunity or other health-debilitating conditions.
4. Insight into the possible incoming novel mutations of the coronavirus that might lead to further infections that won’t be recognized by immunized and previously infected individuals.

Advantages

1. Unlike previous approaches, this approach provided highly specific findings of the viral changes that can provide much-needed specificity for diagnosing, treating, and vaccinating the general population.
2. Tracking the changes in the development of different viral strains give novel insight into the evolution of this virus, providing a future-proof approach to prepare for highly possible future endemics of coronavirus.
3. The potential for further expanding the results to understand the hotspots and mechanisms of viruses in general, and coronavirus specifically, in evading the immune response in humans.