SPIKENET: Developing a First-in-Class Therapeutic for Acute and Long COVID
UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE
MICHAEL J. PAIDAS, MD
Principal Investigator · Professor & Chair, Dept. of Obstetrics, Gynecology & Reproductive Sciences · University of Miami
ARUMUGAM R. JAYAKUMAR, PhD
Co-Principal Investigator · Neuroscientist & Expert in MHV-1 Mouse Models · University of Miami
Background & rationale
As of mid-2025, there are no FDA-approved treatments for Long COVID. SPIKENET (SPK) is a 15-amino acid synthetic peptide invented by Drs. Paidas and Jayakumar, designed to prevent viral binding to host receptors. Funded by the Charles M. Vallee Foundation since 2023, preclinical studies in established mouse models of coronavirus have demonstrated SPK's ability to treat both acute and long COVID — even when administered long after infection. This makes it the only known compound with demonstrated efficacy across both disease phases.
Major findings from Vallee Foundation funding (2023–2025)
Neuronal protection. SARS-CoV-2 proteins interact with two major neuronal proteins, ATP1A1 and SLC3A2, causing protein aggregation and neuronal death. SPIKENET significantly reduced this interaction and reversed protein loss, strongly implicating this pathway in long-term neurological deficits.
Alzheimer's-like pathology in long COVID. At 12 months post-infection, mice showed neurofibrillary tangles, elevated p-Tau181, increased amyloid beta-42, Lewy bodies, and gene expression changes consistent with mixed dementia — including Alzheimer's, vascular, and Lewy body dementia. A total of 450 up- and down-regulated genes were identified.
Lung-brain axis. Increased lung NMDA receptors post-infection stimulate FGF2 release, disrupting the blood-brain barrier and allowing immune cell infiltration. SPIKENET normalized NMDA receptor and surfactant A levels in both lung and brain.
Congenital malformations. MHV-1 infection in pregnant mice caused major congenital defects in offspring — brain/face malformations, neural tube defects, and abdominal wall defects — none of which were observed in pups born to SPK-treated mothers.
Multi-organ protection. SPK demonstrated therapeutic benefit across multiple organ systems: restoring kidney gene expression profiles to near-normal after long COVID–associated fibrosis and tubular dysfunction; and mitigating intestinal damage, villous atrophy, and inflammatory bowel–like changes in the small intestine (published, Viruses 2024).
Behavioral recovery. SPK reversed motor and cognitive deficits in mice infected with both high and low doses of MHV-1, and critically, produced behavioral recovery even when administered at days 50, 100, and 220 post-infection — suggesting efficacy in treating established long COVID.
Initial safety data. Subcutaneous SPK injections at 2, 5, and 10 mg/kg — including repeated dosing — showed no effect on animal survival, clinical symptoms, or body weight. Comprehensive biochemical and histological toxicity studies remain to be completed.
SPIKENET: An Evidence-based Therapy for Long COVID Elumalai et al., Viruses, 2024 → https://doi.org/10.3390/v16060838
Acute and Long COVID Intestinal Changes in an Experimental Model of Coronavirus in Mice Hussain et al., Viruses, 2024 → https://doi.org/10.3390/v16060832
Kidney Damage in Long COVID: Studies in Experimental Mice Ramamoorthy et al., Biology, 2023 → https://doi.org/10.3390/biology12081070
A Mouse Model of MHV-1 Virus Infection for Study of Acute and Long COVID Infection Masciarella et al., Current Protocols, 2023 → https://doi.org/10.1002/cpz1.896
Dermatologic Changes in Experimental Model of Long COVID Hussain et al., Microorganisms, 2024 → https://doi.org/10.3390/microorganisms12020272
