Background: Severe Acute Respiratory Syndrome (SARS) coronavirus 2 (SARS-CoV-2) is responsible for the 2019 coronavirus epidemic (COVID-19). SARS-CoV-2 infection is associated with high mortality and morbidity worldwide. By Dec 1, 2022, over 643 million cases have been reported worldwide, with 6.63 million people lost their lives. A common sequela is chronic neurologic diseases, which severely impact the quality of life and increase the burden on healthcare systems. The Post-COVID, or Long COVID neurologic symptoms are due to the robust replication of SARS-CoV-2 in the nasal neuroepithelial cells, leading to neuroinvasion and inflammation of the central nerve system (CNS). Currently used medications and vaccines are not targeting the neuroinvasion of SARS-CoV-2, and these methods do not inhibit the robust SARS-CoV-2 replication in the nasal epithelial cells. Therefore, a significant gap in treatment/preventive strategies that needs to be filled is to rapidly inhibit SARS-CoV-2 replication in the nasal cavity to block viral invasion to CNS, in order to minimize neurologic damages. We hypothesize that EGCG-palmitate (EC16), a compound with a broad spectrum of antiviral activities, has potential to become a new drug agent against SARS-CoV-2 replication in nasal epithelial cells, thereby minimizing post COVID neurologic symptoms.
Method: Formulations suitable for intranasal applications were developed and tested in vitro against human α coronavirus 229E (CoV-229E) and β coronavirus OC43 (CoV-OC43) using TCID50 assay. Formulations met the FDA standard with the highest antiviral activity were selected for further improvement in stability and homogeneity. The final formulation (#18) suitable for animal and human tests was selected and tested in comparison of Remdesivir in cell culture infection systems following two test protocols (with or without direct contact with the virus).
Results: The initial results demonstrate that EC16 formulations in normal saline, phosphate buffered saline, and cell culture medium effectively inhibited human coronavirus infection (>99%) after a single application, with or without direct contact with the virus. The final formulation #18 was able to inhibit viral infectivity by >99.99%, exceeding the efficacy of Remdesivir. To the best of our knowledge, this result represents the first approach using EC16-containing nasal formulations to inhibit human coronavirus. Future studies are planned to investigate the in vitro and in vivo efficacy against SARS-CoV-2 variants (on going) and suitability for clinical trials toward new drug application.
Conclusion: With its, antiviral, antioxidant, anti-inflammatory, and neuroprotective properties, EC16 in nasal formulations could be further developed for clinical applications to COVID-19 patients for minimizing Long COVID neurologic symptoms.
- Upon completion, participant will be able to
- Understand the neurologic symptoms caused by SARS-CoV-2 infection.
- Understand how natural and non-toxic compounds could be applied in antiviral nasal formulations.
- Understand the advantages of nasal drug delivery to combat respiratory virus infection and protect the brain from virus-induced damages.
- Gain knowledge of new technologies and novel formulations developed to prevent neurologic symptoms