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Researchers from the Indian Institute of Science Education and Research (IISER) Bhopal have demonstrated that proteins from the Covid-19 virus other than the well-known ‘spike protein’ can play a critical role in the infectivity of the virus.
The study was led by Dr. Ajit Chande, Assistant Professor, Department of Biological Sciences, IISER Bhopal. The results of this work have recently been published in the peer-reviewed journal Frontiers in Cellular and Infection Microbiology.
The SARS-CoV-2 virus has an RNA genome, surrounded by a sphere-shaped structure. This structure comprises various types of proteins, with one of them being the ‘spike protein’ that gives the virus its characteristic spiked look or ‘crown’. Since the virus is highly infectious, most studies do not use the live virus, but use a similar protein capsule made up of spike that has been filled with another viral core, in a process called ‘pseudotyping.’
Elaborating on his research, Dr. Ajit Chande said, “Current methods of retrovirus pseudotyping are focused on the spike protein of the virus. Our study picks off from this point.”
While only the spike protein is commonly used for pseudotyping when one wants to study viral entry process or the neutralizing antibody responses, the IISER Bhopal team was curious to see if including the other SARS CoV-2 proteins would influence pseudotyped virion infectivity. This was motivated by the fact that in a real-world scenario, the spike protein does not operate in isolation, but in conjunction with other viral proteins that are engaged in various auxiliary roles during the course of infection.
The team combined a type of virus vector called the lentivirus with a Covid-19 spike protein to produce ‘spike lentiviruses.’ Twenty-four different SARS CoV-2 viral proteins were included in the pseudovirus ensemble, along with a fluorescent reporter to detect the infected cells.
“We believe that the N-protein promotes the incorporation of the spike protein into viral particles, thereby increasing the chances for each viral particle to bind to the target cell. Our discovery opens up an exciting host of questions for related research in this area,” added Dr. Chande.
This important research shows that it is not enough to study the spike protein alone for developing therapeutic drugs, neutralizing antibodies, and entry inhibitors, since the actual infectivity levels may vary significantly based on the presence of core proteins like the N protein.