Algesic activity of the human coronavirus OC43 derived peptide

The human coronavirus OC43 is responsible for 15-30% of seasonal “common cold” infections with typically mild respiratory symptoms. We demonstrated that the coronavirus OC43 derived small peptide encoded by the viral p65 proteins may exhibit molecular mimicry with the pro-algesic fragment of Myelin Basic Protein (MBP). After intrasciatic injection, the p65-derived peptide induced robust pain hypersensitivity in rats lasting for up to 21 days. Transcriptomic analysis at day 21 revealed extensive spinal up-regulation of pro-nociceptive genes. Strikingly, genome-wide isoform switching due to activation of transcriptional start sites and alternative splicing events has occurred. We hypothesized that the coronavirus-derived peptides can dysregulate MBP function in the PNS/CNS and promote neuropathic chronic pain. Our findings offer paradigm-shifting mechanistic understanding of the viral origin of idiopathic neurological effects including chronic neuropathic pain, a condition currently refractory to therapeutic treatment. This new knowledge will lead to new diagnostic, prognostic, and therapeutic approaches to benefit patients with chronic pain. Overall design: Compare rat spinal cord transcriptomes after sciatic nerve injections to identify upstream regulators and signaling pathways induced due to molecular mimicry with the coronavirus-derived peptide