As the COVID-19 pandemic continues, people around the world are waiting for effective treatments and vaccines. To develop them, scientists will need to understand fundamental aspects of the biology of SARS-CoV-2, the virus that causes COVID-19. Peter McPherson’s lab at The Neuro is using its expertise in cell biology to investigate one important part of the story – how the virus enters human cells.
All viruses work by infecting host cells with their genetic material. In the case of SARS-CoV-2, it uses ribonucleic acid (RNA), which once introduced into the cell, hijacks the cell machinery, forcing the cell to make new copies of the virus.
The way SARS-CoV-2 implants its RNA into cells remains unclear, but there are two main theories. The first is that the lipid membrane of the virus fuses with the plasma membrane on the surface of the cell, allowing transfer of its RNA into the cell. The second is that the entire virus particle enters the cell as a whole before transferring its RNA, a process called endocytosis.
McPherson and three of his research colleagues are testing the second theory, and their experience working on the cell biology of neurological disease gives them a head start. They have studied endocytosis in numerous disorders, including Parkinson’s disease (PD). In PD patients, a misfolded version of the protein alpha-synuclein enters neurons much like a virus. Once inside the cell, the alpha-synuclein particles accumulate to form toxic clumps that cause damage. Understanding how misfolded alpha-synuclein enters neurons is key to stopping spread of the disease.
When the pandemic began, McPherson started to build and accumulate the reagents – or ingredients –needed to study COVID-19 and began researching the virus.
“Endocytosis is something I’ve been researching since I was a postdoctoral fellow,” he says. “It doesn’t matter if it’s a virus or otherwise. The mechanism is the same. The underlying biological process is very similar to other endocytic mechanisms we have studied for the past 25 years.”
If they find SARS-CoV-2 uses endocytosis to enter cells, they will test six Federal Drug Administration-approved drugs to see if they block endocytosis. Each of the six drugs have already been shown to influence endocytic mechanisms.
“We all need to contribute to this fight as we are best equipped,” said McPherson. “Like everyone, I was sequestered at home thinking perhaps I should volunteer in some way when I thought, ‘why not do what I do best.’ If we can show SARS-CoV-2 uses an endocytic mechanism it can open up new paths to drug screening. We all must do our part.”