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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

The Scan

International Team Proposes Checklist for Returning Genomic Research Results

Researchers in the European Journal of Human Genetics present a checklist to guide the return of genomic research results to study participants.

Study Presents New Insights Into How Cancer Cells Overcome Telomere Shortening

Researchers report in Nucleic Acids Research that ATRX-deficient cancer cells have increased activity of the alternative lengthening of telomeres pathway.

Researchers Link Telomere Length With Alzheimer's Disease

Within UK Biobank participants, longer leukocyte telomere length is associated with a reduced risk of dementia, according to a new study in PLOS One.

Nucleotide Base Detected on Near-Earth Asteroid

Among other intriguing compounds, researchers find the nucleotide uracil, a component of RNA sequences, in samples collected from the near-Earth asteroid Ryugu, as they report in Nature Communications.