SARS-CoV-2, herpes that creates COVID-19, can reduce pain, according to a brand new review by University of Arizona Health Sciences scientists.
The finding might explain why nearly 1 / 2 of those who get COVID-19 experience few or no symptoms, though they could spread the condition even, in line with the study’s corresponding author Rajesh Khanna, PhD, a professor in the school of Treatments — Tucson’s Department of Pharmacology.
“It made plenty of sense in my experience that perhaps the basis for the unrelenting distribute of COVID-19 is that in early stages, you’re travelling all fine like there’s nothing wrong because your soreness has been suppressed,” mentioned Dr. Khanna. “You possess the virus, however, you don’t feel negative because you pain is finished. If we could prove that this treatment is how you get COVID-19 to propagate further, that’s of massive value.”
The paper, “SARS-CoV-2 Spike protein co-opts VEGF-A/Neuropilin-1 receptor signaling to induce analgesia,” will soon be published in PAIN, the journal of the International Association for the scholarly study of Discomfort.
The U.S. Centers for Disease Prevention and Control released updated data Sept. 10 estimating 50% of COVID-19 transmission occurs ahead of the onset of symptoms and 40% of COVID-19 infections are asymptomatic.
” the chance is raised by This research, being an early symptom of COVID-19, might be reduced by the SARS-CoV-2 spike protein because it silences your body’s pain signaling pathways,” said UArizona Health Sciences Senior Vice President Michael D. Dake, MD. “University of Arizona Health Sciences researchers at the Comprehensive Pain and Addiction Center are leveraging this excellent finding to explore a novel class of therapeutics for pain even as we continue steadily to seek new approaches to address the opioid epidemic.”
Viruses infect host cells through protein receptors on cell membranes. In the pandemic early, scientists established that the SARS-CoV-2 spike protein uses the angiotensin-converting enzyme 2 (ACE2) receptor to enter your body. In June but, two papers posted on the preprint server bioRxiv pointed to neuropilin-1 as an additional receptor for SARS-CoV-2.
“That caught our eye because the past 15 years my lab has been studying a complex of proteins and pathways that connect with pain processing which can be downstream of neuropilin,” said Dr. Khanna, who’s associated with the UArizona Health Sciences Comprehensive Pain and Addiction Center and is just a person in the UArizona BIO5 Institute. “So we stepped back and realized this might signify maybe the spike protein is associated with some kind of pain processing.”
Many biological pathways signal the physical body to feel pain. One is via a protein named vascular endothelial growth factor-A (VEGF-A), which plays a vital role in blood vessel growth but has been connected to diseases such as for instance cancer also, rheumatoid arthritis and, of late, COVID-19.
Like an integral in a lock, when VEGF-A binds to the receptor neuropilin, it initiates a cascade of events causing the hyperexcitability of neurons, leading to pain. Dr. Khanna and his research team unearthed that the SARS-CoV-2 spike protein binds to neuropilin in the identical location as VEGF-A.
With that knowledge, they performed some experiments in the laboratory and in rodent models to try their hypothesis that the SARS-CoV-2 spike protein acts on the VEGF-A/neuropilin pain pathway. They used VEGF-A as a trigger to induce neuron excitability, which creates pain, added the SARS-CoV-2 spike protein then.
“Spike completely reversed the VEGF-induced pain signaling,” Dr. Khanna said. “It didn’t matter if we used quite high doses of spike or extremely low doses — it reversed the pain completely.”
Dr. Khanna is teaming up with UArizona Health Sciences immunologists and virologists to carry on research to the role of neuropilin in the spread of COVID-19.
In his lab, he will be examining neuropilin as a fresh target for non-opioid treatment. During the scholarly study, Dr. Khanna tested existing small molecule neuropilin inhibitors developed to suppress tumor growth using cancers and found they provided exactly the same pain relief since the SARS-CoV-2 spike protein when binding to neuropilin.
“We are dancing with designing small molecules against neuropilin, natural compounds particularly, that could be essential for treatment,” Dr. Khanna said. “We’ve a pandemic, and we’ve 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 taking a look at neuropilin as a brand new non-opioid approach to fight the opioid epidemic.”
Co-authors on the paper from the Department of Pharmacology are: Aubin Moutal, PhD; Lisa Boinon; Kimberly Gomez, PhD; Dongzhi Ran, PhD; Yuan Zhou; Harrison Stratton, PhD; Song Cai, PhD; Shizhen Luo; Kerry Beth Gonzalez; and Samantha Perez-Miller, PhD. Co-authors from the Department of Anesthesiology with additional affiliations with the Comprehensive Addiction and Pain Center are Amol Patwardhan, MD, PhD, and Mohab Ibrahim, MD, PhD.