A Novel Vaccine Employing Non-Replicating Rabies Virus Expressing Chimeric SARS-CoV-2 Spike Protein Domains: Functional Inhibition of Viral/Nicotinic Acetylcholine Receptor Complexes
| Autor: | Michelle L. Stefano, Richard M. Kream, George B. Stefano |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
COVID-19 Vaccines
viruses Hepatitis C virus Pneumonia Viral Short Communications Receptors Nicotinic 030204 cardiovascular system & hematology Biology Virus Replication medicine.disease_cause Virus Betacoronavirus 03 medical and health sciences 0302 clinical medicine Protein Domains medicine Humans Pandemics Ebolavirus Vaccines SARS-CoV-2 Viral Vaccine Rabies virus COVID-19 virus diseases Viral Vaccines General Medicine Virology Coronavirus Nicotinic acetylcholine receptor Capsid Viral replication 030220 oncology & carcinogenesis Spike Glycoprotein Coronavirus Coronavirus Infections |
| Zdroj: | Medical Science Monitor : International Medical Journal of Experimental and Clinical Research |
| ISSN: | 1643-3750 |
| DOI: | 10.12659/msm.926016 |
| Popis: | The emergence of the novel β-coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a global pandemic of coronavirus disease 2019 (COVID-19). Clinical studies have documented that potentially severe neurological symptoms are associated with SARS-CoV-2 infection, thereby suggesting direct CNS penetration by the virus. Prior studies have demonstrated that the destructive neurological effects of rabies virus (RABV) infections are mediated by CNS transport of the virus tightly bound to the nicotinic acetylcholine receptor (nAChR). By comparison, it has been hypothesized that a similar mechanism exists to explain the multiple neurological effects of SARS-CoV-2 via binding to peripheral nAChRs followed by orthograde or retrograde transport into the CNS. Genetic engineering of the RABV has been employed to generate novel vaccines consisting of non-replicating RABV particles expressing chimeric capsid proteins containing human immunodeficiency virus 1 (HIV-1), Middle East respiratory syndrome (MERS-CoV), Ebolavirus, and hepatitis C virus (HCV) sequences. Accordingly, we present a critical discussion that integrates lessons learned from prior RABV research and vaccine development into a working model of a SARS-CoV-2 vaccine that selectively targets and neutralizes CNS penetration of a tightly bound viral nAChR complex. |
| Databáze: | OpenAIRE |
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