SARS-CoV-2 may spur growth of molecular “railways” out of infected cells, School scientists show

UCSF scientists and international collaborators have uncovered new details about how SARS-CoV-2, the virus that causes COVID-19, takes control of human cells to replicate and spread, findings that point to new potential therapies.

The work was carried out by a collaboration based at the UCSF Quantitative Biosciences Institute (QBI). The QBI Coronavirus Research Group (QCRG) was founded in March under the leadership of QBI Director Nevan Krogan, PhD, who recruited dozens of faculty members at UCSF and abroad to identify existing drugs that might be effective in fighting COVID-19.

QBI is an organized research unit in the School of Pharmacy. Krogan is a faculty member in the School of Medicine and a senior investigator at the Gladstone Institutes.

The research, which was published on June 23 in Cell, showed that SARS-CoV-2 hijacks a large family of human enzymes, known as kinases, to orchestrate the virus’s own replication and spread. The team also showed that the virus uses these human kinases to spur the growth of tentacle-like structures, known as filopodia, which sprout from infected cells.

Collaborators at Rocky Mountain Laboratories, operated by the National Institute of Allergy and Infectious Diseases, used electron microscopy to capture the first-ever images of viral particles “budding” from filopodia, suggesting that these cellular protrusions may be used as “railways” for transporting SARS-CoV-2 out of infected cells.

Drugs that block kinase activity or the growth of filopodia were then shown to suppress viral growth in the laboratory, raising the possibility that a combination of these drugs might be effective in treating COVID-19 in patients.

More

• COVID-19 Relies on Cell’s ‘Master Regulators’ for Survival (UCSF News)
• The Global Phosphorylation Landscape of SARS-CoV-2 Infection (Cell)