Why the lower reported prevalence of asthma in patients diagnosed with COVID-19 validates repurposing EDTA solutions to prevent and manage treat COVID-19 disease
Fecha
2020Autor
Cashman, Daniel P.
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Resumen
There currently is no specific antiviral drug or a vaccine for SARS-CoV-2/COVID-19 infections; now exceeding 10,300,000 infections worldwide. In the absence of
animal models to test drugs, we need to find molecular explanations for any unforeseen peculiarities in clinical data, especially the recent reports describing an
unexpected asthma paradox. Asthma is considered a high medical risk factor for susceptibility to SARS-CoV-2/COVID-19 infection, yet asthma is not on the list of top
10 chronic health problems suffered by people who died from SARS-CoV-2/COVID-19. Resolving this paradox requires looking beyond the binary model of a viral
receptor-binding domain (RBD) attaching to the ACE-2 receptor. A pBlast analysis revealed that the SARS-CoV-2 surface spike protein contains two calciumdependent fusion domains that were recently discovered SARS-CoV-1. These viral calcium-dependent binding domains can facilitate membrane fusion only after
cleavage by the host surface protease TMPRSS2. Importantly, TMPRSS2 also requires calcium for its SRCR (scavenger receptor cysteine-rich) domain and
its LDLRA (LDL receptor class A) domain. Thus, the presence of EDTA excipients in nebulized β2-agonist medicines can disrupt SARS-CoV-2/COVID-19 infection and
can explain the asthma paradox. This model validates repurposing EDTA in nebulizer solutions from a passive excipient to an active drug for treating COVID-19
infections. Repurposed EDTA delivery to respiratory tissues at an initial target dose of 2.4 mg per aerosol treatment is readily achievable with standard nebulizer and
mechanical ventilator equipment. EDTA warrants further investigation as a potential treatment for SARS-CoV-2/COVID-19 in consideration of the new calcium
requirements for virus infection and the regular presence of EDTA excipients in common asthma medications such as Metaproterenol. Finally, the natural history of
Coronavirus diseases and further analysis of the fusion loop homologies between the Betacorona SARS-CoV-2 virus and the less pathogenic Alphacorona HC0V-229E
virus suggest how to engineer a hybrid virus suitable for an attenuated alpha-beta SARS-CoV-2/COVID-19 vaccine. Thus, replacing SARS-CoV-2 fusion loops (amino
acids 816–855) with the less pathogenic HCoV-229E fusion loop (amino acids 923–982) may provide antigenicity of COVID-19, but limit the pathogenicity to the
level of HCoV-229E.
Palabras clave
COVID-19; EDTA solutions; COVID-19 diseaseEnlace al recurso
https://doi.org/10.1016/j.mehy.2020.110027Colecciones
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