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New study finally demystifies the most bizarre coronavirus side effect

Published Oct 6th, 2020 11:49AM EDT
Coronavirus Symptoms
Image: Maria Sbytova/Adobe

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  • Researchers have discovered one of the most bizarre side effects of the novel coronavirus: The pathogen can inhibit a protein involved in pain signaling, effectively acting as a pain reliever.
  • The spike protein that the virus uses to infect cells can also bind to a protein called neuropilin-1 that mediates pain. This process explains why some COVID-19 patients do not feel any pain while fighting the disease.
  • The study may have significant implications on the future of pain relief medication, helping researchers fight a different health crisis: The opioid crisis.

The novel coronavirus might not have a mind of its own, but the pathogen certainly seems to act as if it’s planning a well-coordinated attack on the human body. Studies revealed months ago that the virus can block the local production of interferon, robbing cells of the ability to delay the infection until more reinforcements from the immune system can come to the rescue. More research that followed also showed that interferon imbalances might kill people who are otherwise perfectly healthy. Genetic issues related to interferon that went undetected because they have no symptoms can surface from the COVID-19 infection and cause serious problems.

It turns out that the virus doesn’t just mess with interferon. A new study shows yet another sneaky capability of the virus that can explain why so many people are asymptomatic. What’s even more interesting is that the discovery might actually have an incredible upside: It could help researchers develop a solution to the ongoing opioid crisis that claims so many lives each year.

Pain is a clever defense mechanism of the human body. It may be annoying, but pain signals some sort of immediate danger that requires your attention. Whether it’s an outside issue that’s harming your body or pain comes from inside you, the pain mechanism alerts one’s brain that something is wrong and action is required.

The COVID-19 infection also includes pain among its symptoms. Whether it’s headaches or muscle aches, it’s still a version of pain that’s telling you something isn’t right. But it turns out that the same SARS-CoV-2 component that’s used to infect cells can also bind to a key protein that’s part of the pain signaling process. It’s the virus’s spike protein, which scientists are desperately trying to neutralize with vaccines, monoclonal antibodies, and other antiviral meds.

Researchers from the University of Arizona Health Sciences published a study in Pain magazine (via NeuroScienceNews) that explains how the virus interferes with pain pathways.

“It made a lot of sense to me that perhaps the reason for the unrelenting spread of COVID-19 is that in the early stages, you’re walking around all fine as if nothing is wrong because your pain has been suppressed,” Dr. Rajesh Khanna told NeuroScienceNews. “It made a lot of sense to me that perhaps the reason for the unrelenting spread of COVID-19 is that in the early stages, you’re walking around all fine as if nothing is wrong because your pain has been suppressed.”

The researchers took note of earlier studies that said the SARS-CoV-2 spike protein can bind to neuropilin-1 in addition to the ACE2 receptor the spike uses to infect cells.

“That caught our eye because, for the last 15 years, my lab has been studying a complex of proteins and pathways that relate to pain processing that are downstream of neuropilin,” Khanna said. “So we stepped back and realized this could mean that maybe the spike protein is involved in some sort of pain processing.”

The scientists came to the realization that the spike protein interacts with a specific pain pathway. A protein named vascular endothelial growth factor-A (VEGF-A) links to neuropilin-1, and the process ultimately leads to the symptom of pain. But if SARS-CoV-2 blocks the neuropilin-1 receptor, then the sequence of events that would normally result in pain is blocked.

The scientists conducted experiments showing that the spike protein binds to neuropilin-1 in the same location as VEGF-A. Their experiment used VEGF-A to trigger neuron excitability in rodents, which led to pain. Then they added the SARS-CoV-2 protein. “The spike protein completely reversed the VEGF-induced pain signaling,” Dr. Khanna said. “It didn’t matter if we used very high doses of spike or extremely low doses—it reversed the pain completely.”

Like other COVID-19 studies, the University of Arizona’s research can certainly benefit from additional studies. But if these conclusions are accurate, then we might finally know why some people do not have symptoms involving pain while they battle a COVID-19 infection.

More interestingly, this COVID-19 conclusion could lead to new discoveries for pain mitigation in other illnesses that come with chronic pain. The researchers plan to design small molecules that can block neuropilin, “particularly natural compounds, that could be important for pain relief,” Khanna sale. “We have a pandemic, and we have an opioid epidemic. They’re colliding. Our findings have massive implications for both. SARS-CoV-2 is teaching us about viral spread, but COVID-19 has us also looking at neuropilin as a new non-opioid method to fight the opioid epidemic.”

Chris Smith Senior Writer

Chris Smith has been covering consumer electronics ever since the iPhone revolutionized the industry in 2008. When he’s not writing about the most recent tech news for BGR, he brings his entertainment expertise to Marvel’s Cinematic Universe and other blockbuster franchises.

Outside of work, you’ll catch him streaming almost every new movie and TV show release as soon as it's available.

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