Beyond the Spike Protein

SARS-CoV-2, the virus that causes COVID-19, breaks into human cells using a protein called “spike.” Research from the UCSF Quantitative Biosciences Institute (QBI) shows that mutations beyond the spike protein, in other viral proteins, may also help more-infectious variants evade the immune system and spread rapidly.

“The mutations in spike allow the virus to get into cells more effectively. But what about after the virus gets into cells? There may be other mutations that allow it to replicate more,” said Nevan Krogan, PhD, co-senior author on the paper and director of QBI and its Coronavirus Research Group (QCRG).

QBI is an organized research unit in the UCSF School of Pharmacy.

The findings, published on December 23 in Nature, open the door to the development of new COVID-19 therapies, with immediate implications for several variants of SARS-CoV-2, including Alpha, Delta, and Omicron. The work is the result of an international collaboration led by scientists at QBI and University College of London.

“Studying the variants of concern gives us ideas about how SARS-CoV-2 evolves,” said UCSF postdoctoral scholar Mehdi Bouhaddou, PhD, co-first author on the paper. “Now we have a sense of the proteins that are mutating most frequently, and the biological consequences of those mutations. I think this helps us prepare for what might come next.”

Written by Levi Gadye for the UCSF School of Pharmacy