Hutch Team Develops Platform for Assessing Impact of SARS-CoV-2 Spike Mutations

A platform that measures how mutations across the SARS-CoV-2 spike protein affect the viral infectiousness is reported in Cell this week. In addition to providing insights into SARS-CoV-2, the system can be extended to other viruses, according to the Fred Hutchinson Cancer Center-led team that developed it. The SARS-CoV-2 spike protein, which enables viral entry into host cells, is a key target of neutralizing antibodies against the virus. However, it has undergone rapid evolution, eroding the potency of serum neutralization and enabling escape from most monoclonal antibodies. The Fred Hutch-led team developed a deep mutational scanning platform based on non-replicative pseudotyped lentiviruses to directly quantify how large numbers of spike mutations affect antibody neutralization and pseudovirus infection. They demonstrate how the platform works by producing libraries of the Omicron BA.1 and Delta spikes, which they used to map escape mutations from neutralizing antibodies targeting the receptor-binding domain, N-terminal domain, and S2 subunit of the spike protein. The researchers note that the system is applicable to any virus with an entry protein amenable to lentiviral pseudotyping including other coronaviruses, influenza viruses, filoviruses, arenaviruses, and henipaviruses. "Deep mutational scanning of the entry proteins of all these viruses could provide valuable information for antigenic surveillance and vaccine design since these proteins are the dominant target of neutralizing antibodies," they write