A Treatment to Eliminate SARS-CoV-2 Replication in Human Airway Epithelial Cells Is Safe for Inhalation as an Aerosol in Healthy Human Subjects.
BACKGROUND: Low airway surface pH is associated with many airway diseases, impairs antimicrobial host defense, and worsens airway inflammation. Inhaled Optate is designed to safely raise airway surface pH and is well tolerated in humans. Raising intracellular pH partially prevents activation of SARS...
| Publicado en: | Respiratory Care Vol. 66; no. 1; pp. 113 - 120 |
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| Autores principales: | , , , , , , , , , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Mary Ann Liebert, Inc.
Jan2021
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=147933480&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 147933480 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00201324 4GG jtl: Respiratory Care issn: 00201324 maglogo: N pubinfo: dt: Jan2021 vid: 66 iid: 1 pid: 1365 pub: Mary Ann Liebert, Inc. place: New Rochelle, New York artinfo: ui: 147933480 147933480 147933480 10.4187/respcare.08425 147933480 ppf: 113 ppct: 7 formats: fmt: @attributes: type: P tig: atl: A Treatment to Eliminate SARS-CoV-2 Replication in Human Airway Epithelial Cells Is Safe for Inhalation as an Aerosol in Healthy Human Subjects. aug: au: Davis, Michael D. Clemente, Tatiana M. Giddings, Olivia K. Ross, Kristie Cunningham, Rebekah S. Smith, Laura Simpson, Edward Yunlong Liu Kloepfer, Kirsten Ramsey, I. Scott Yi Zhao Robinson, Christopher M. Gilk, Stacey D. Gaston, Benjamin affil: Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine sug: subj: SARS-CoV-2 Physiology Epithelial Cells Aerosols Administration, Inhalation Coronavirus Infections Microbiology Microbiologic Phenomena Human Cell Viability ab: BACKGROUND: Low airway surface pH is associated with many airway diseases, impairs antimicrobial host defense, and worsens airway inflammation. Inhaled Optate is designed to safely raise airway surface pH and is well tolerated in humans. Raising intracellular pH partially prevents activation of SARS-CoV-2 in primary normal human airway epithelial (NHAE) cells, decreasing viral replication by several mechanisms. METHODS: We grew primary NHAE cells from healthy subjects, infected them with SARS-CoV-2 (isolate USA-WA1/2020), and used clinical Optate at concentrations used in humans in vivo to determine whether Optate would prevent viral infection and replication. Cells were pretreated with Optate or placebo prior to infection (multiplicity of infection = 1), and viral replication was determined with plaque assay and nucleocapsid (N) protein levels. Healthy human subjects also inhaled Optate as part of a Phase 2a safety trial. RESULTS: Optate almost completely prevented viral replication at each time point between 24 h and 120 h, relative to placebo, on both plaque assay and N protein expression (P < .001). Mechanistically, Optate inhibited expression of major endosomal trafficking genes and raised NHAE intracellular pH. Optate had no effect on NHAE cell viability at any time point. Inhaled Optate was well tolerated in 10 normal subjects, with no change in lung function, vital signs, or oxygenation. CONCLUSIONS: Inhaled Optate may be well suited for a clinical trial in patients with pulmonary SARS-CoV-2 infection. However, it is vitally important for patient safety that formulations designed for inhalation with regard to pH, isotonicity, and osmolality be used. An inhalational treatment that safely prevents SARS-CoV-2 viral replication could be helpful for treating patients with pulmonary SARS-CoV-2 infection. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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