Dose-Dependent Respiratory Viral Inhibition by a Safe Inhaled Alkaline Treatment
American Journal of Respiratory and Critical Care Medicine
; 205(1), 2022.
Article
in English
| EMBASE | ID: covidwho-1927705
ABSTRACT
Introduction:
SARS-CoV-2 respiratory infection is pandemic and continues to cause significant mortality and morbidity worldwide. Respiratory viral infections in general are a leading cause of hospital admissions and mortality throughout the world as well. Most respiratory viral infections require an acidic intracellular and endosomal environment in order to enter host cells, replicate, and cause illness. We study the beneficial effects of airway alkalinization by an inhaled drug, Optate, that we currently have demonstrated is safe to inhale by healthy subjects and those with stable airways disease. We have recently shown that treatment with 4.5 mg/ml Optate safely inhibits SARS-CoV-2 infection in primary human airway epithelial cells (HAECs). We hypothesized that this inhibition would be dose dependent and that Optate would also inhibit other viral infections in a dosedependent manner.Methods:
HAECs were infected with respiratory syncytial virus with green fluorescent protein (RSV-GFP) or SARS-CoV-2 virus. A dose-response curve of Optate was performed in each infection model and compared to a control group. Viral infection was quantified using fluorescence microscopy, plaque assays, and viral protein quantification. Optate pH was measured at each dose and a corresponding dose/pH curve was calculated to compare pH to dose-response.Results:
SARS-CoV-2 infection was significantly inhibited by doses of Optate > 2.25 mg/ml, corresponding with an Optate pH > 9.2 (n = 4, p < 0.001). RSV infection was significantly inhibited by doses of Optate > 2 mg/ml, corresponding with an Optate pH > 9 (n = 3, p < 0.001). No significant difference was noted between control and Optate treated HAECs at lower concentrations of Optate.Conclusions:
Optate inhibits SARS-CoV-2 and RSV viral infections in a dose-dependent manner that correlates with Optate pH. These findings suggest that Optate may be an inhaled therapeutic for patients with respiratory viral infections. (Table Presented).
green fluorescent protein; viral protein; adult; airway epithelium cell; alkalinization; case report; clinical article; conference abstract; coronavirus disease 2019; dose response; female; fluorescence microscopy; human; human cell; human tissue; male; nonhuman; pH; plaque assay; respiratory syncytial virus infection; respiratory tract disease; Severe acute respiratory syndrome coronavirus 2; viral respiratory tract infection; virus inhibition
Full text:
Available
Collection:
Databases of international organizations
Database:
EMBASE
Language:
English
Journal:
American Journal of Respiratory and Critical Care Medicine
Year:
2022
Document Type:
Article
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