Targeting cell’s “trash compactor” could lead to new antiviral strategy to fight COVID-19

Illustration shows coronavirus exit pathway through the lysosome.
Credit: NIH Medical Arts

Researchers at the National Institutes of Health have discovered a biological pathway that the novel coronavirus appears to use to hijack and exit cells as it spreads through the body. A better understanding of this important pathway may provide vital insight in stopping the transmission of the virus—SARS-CoV-2—which causes COVID-19 disease.

In cell studies, the researchers showed for the first time that the coronavirus can exit infected cells through the lysosome, an organelle known as the cells “trash compactor.” Normally the lysosome destroys viruses and other pathogens before they leave the cells. However, the researchers found that the coronavirus deactivates the lysosome’s disease-fighting machinery, allowing it to freely spread throughout the body.

“These coronaviruses are very sneaky,” said study co-author Nihal Altan-Bonnet, Ph.D., chief of the Laboratory of Host-Pathogen Dynamics at the NIH’s National Heart, Lung, and Blood Institute. “They’re using these lysosomes to get out, but they’re also disrupting the lysosome so it can’t do its job or function.”

Targeting this lysosomal pathway could lead to the development of new, more effective antiviral therapies to fight COVID-19. The authors have already identified one experimental enzyme inhibitor that potently blocks coronaviruses from getting out of the cell. The findings, funded by NHLBI and also supported by other NIH grants, appear in the journal Cell