UC Berkeley scientists find a COVID virus protein that sets off sneezing, coughing and pain by switching on nerves directly, in mice
Drugs already made to block the protein might one day ease coughs and help slow spread, the lead scientist says. None has been tested for that.
A protein made by the virus that causes COVID-19 can switch on the nerves behind sneezing, coughing and aches all by itself, without waiting for the body’s immune system to react, UC Berkeley researchers report in a mouse study in the Nov. 13 issue of the journal Neuron, according to a Berkeley news release. Scientists had thought those symptoms came mainly from chemicals released by infected cells and immune cells.
What it could mean
The protein, called PLpro (short for papain-like protease, an enzyme that snips other proteins apart), is a known drug target. Several drugs that block it were developed during the pandemic, though none has been approved for COVID, the release says. Lab leader Diana Bautista said such drugs “could also help treat symptoms like coughing, which could limit viral spread.”
Paxlovid, the COVID pill many people have taken, blocks a different viral enzyme called Mpro. The team found Mpro also sets off sensory nerves, but in a different way.
The researchers say direct nerve activation may help explain lingering long COVID symptoms such as headache, persistent cough, sore throat and chest pain. That idea has not been tested in people.
How they found it
- The team purified PLpro and showed it alone switched on nerve cells in a dish. A version with its cutting ability disabled did nothing.
- A dab of 2 microliters, a tiny droplet, on a mouse’s nose set off up to 30 sneezes a minute; water alone caused about one.
- PLpro works through TRPA1, a sensor on pain-sensing nerves that also makes wasabi and garlic sting. Bautista’s lab discovered that wasabi link in earlier work.
- PLpro from the viruses behind SARS and MERS, two earlier coronavirus outbreaks, also triggered the nerves.
Some reviewers doubted that mice sneeze at all. So Bautista bought a $75,000 plethysmograph, a machine that measures breathing, to record the lung spasms of a sneeze, and her team dyed the liquid blue to measure how much mucus each sneeze sprayed.
Berkeley doctoral student Sonali Mali led the study. Bautista is a professor of molecular and cell biology and a Howard Hughes Medical Institute investigator. An early version was posted online in January 2024 before peer review; the Neuron paper is the reviewed version. The National Institutes of Health and the Howard Hughes Medical Institute paid for the work.
Source: UC Berkeley news release, Nov. 12, 2026; Mali et al., Neuron00813-5); 2024 preprint record, PubMed.