A Treatment to Eliminate SARS-CoV-2 Replication in Human Airway Epithelial Cells Is Safe for Inhalation as an Aerosol in Healthy Human Subjects

References

1. 1.↵
   1. Gaston B,
   2. Kelly R,
   3. Urban P,
   4. Liu L,
   5. Henderson EM,
   6. Doctor A,
   7. et al

   . Buffering airway acid decreases exhaled nitric oxide in asthma. J Allergy Clin Immunol 2006;118(4):817–822.

   OpenUrlCrossRefPubMedWeb of Science
2. 2.↵
   1. Hunt JF,
   2. Fang K,
   3. Malik R,
   4. Snyder A,
   5. Malhotra N,
   6. Platts-Mills TA,
   7. et al

   . Endogenous airway acidification: implications for asthma pathophysiology. Am J Respir Crit Care Med 2000;161(3):694–699.

   OpenUrlCrossRefPubMedWeb of Science
3. 3.↵
   1. Pezzulo AA,
   2. Tang XX,
   3. Hoegger MJ,
   4. Abou Alaiwa MH,
   5. Ramachandran S,
   6. Moninger TO,
   7. et al

   . Reduced airway surface pH impairs bacterial killing in the porcine cystic fibrosis lung. Nature 2012;487(7405):109–113.

   OpenUrlCrossRefPubMedWeb of Science
4. 4.↵
   1. Abou Alaiwa MH,
   2. Reznikov LR,
   3. Gansemer ND,
   4. Sheets KA,
   5. Horswill AR,
   6. Stoltz DA,
   7. et al

   . pH modulates the activity and synergism of the airway surface liquid antimicrobials β-defensin-3 and LL-37. Proc Natl Acad Sci U S A 2014;111(52):18703–18708.

   OpenUrlAbstract/FREE Full Text
5. 5.
   1. Berkebile AR,
   2. McCray PB Jr.

   . Effects of airway surface liquid pH on host defense in cystic fibrosis. Int J Biochem Cell Biol 2014;52:124–129.

   OpenUrlCrossRefPubMed
6. 6.↵
   1. Coakley RD,
   2. Grubb BR,
   3. Paradiso AM,
   4. Gatzy JT,
   5. Johnson LG,
   6. Kreda SM,
   7. et al

   . Abnormal surface liquid pH regulation by cultured cystic fibrosis bronchial epithelium. Proc Natl Acad Sci U S A 2003;100(26):16083–16088.

   OpenUrlAbstract/FREE Full Text
7. 7.↵
   1. Davis MD,
   2. Donn SM,
   3. Ward RM

   . Administration of inhaled pulmonary vasodilators to the mechanically ventilated neonatal patient. Paediatr Drugs 2017;19(3):183–192.

   OpenUrl
8. 8.↵
   1. Davis MD,
   2. Hunt J

   . Exhaled breath condensate pH assays. Immunol Allergy Clin North Am 2012;32(3):377–386.

   OpenUrlPubMed
9. 9.↵
   1. Davis MD,
   2. Walsh BK,
   3. Dwyer ST,
   4. Combs C,
   5. Vehse N,
   6. Paget-Brown A,
   7. et al

   . Safety of an alkalinizing buffer designed for inhaled medications in humans. Respir Care 2013;58(7):1226–1232.

   OpenUrlAbstract/FREE Full Text
10. 10.↵
    1. Ricciardolo FL,
    2. Gaston B,
    3. Hunt J

    . Acid stress in the pathology of asthma. J Allergy Clin Immunol 2004;113(4):610–619.

    OpenUrlCrossRefPubMedWeb of Science
11. 11.
    1. Ngamtrakulpanit L,
    2. Yu Y,
    3. Adjei A,
    4. Amoah G,
    5. Gaston B,
    6. Hunt J

    . Identification of intrinsic airway acidification in pulmonary tuberculosis. Glob J Health Sci 2010;2(1):106–110.

    OpenUrlPubMed
12. 12.↵
    1. Walsh BK,
    2. Davis MD,
    3. Hunt JF,
    4. Kheir JN,
    5. Smallwood CD,
    6. Arnold JH

    . The effects of lung recruitment maneuvers on exhaled breath condensate pH. J Breath Res 2015;9(3):036009.
13. 13.↵
    1. Helenius A

    . Virus entry: what has pH got to do with it? Nat Cell Biol 2013;15(2):125.

    OpenUrlCrossRefPubMed
14. 14.
    1. Hoffmann M,
    2. Kleine-Weber H,
    3. Schroeder S,
    4. Krüger N,
    5. Herrler T,
    6. Erichsen S,
    7. et al

    . SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020;181(2):271–280.e8.

    OpenUrlCrossRefPubMed
15. 15.
    1. Poon LLM,
    2. Peiris M

    . Emergence of a novel human coronavirus threatening human health. Nat Med 2020;26(3):317–319.

    OpenUrl
16. 16.↵
    1. Smith AE,
    2. Helenius A

    . How viruses enter animal cells. Science 2004;304(5668):237–242.

    OpenUrlAbstract/FREE Full Text
17. 17.↵
    1. Davis MD,
    2. Suzaki I,
    3. Kawano S,
    4. Komiya K,
    5. Cai Q,
    6. Oh Y,
    7. Rubin BK

    . Tissue factor facilitates wound healing in human airway epithelial cells. Chest 2019;155(3):534–539.

    OpenUrl
18. 18.↵
    1. Fulcher ML,
    2. Randell SH

    . Human nasal and tracheo-bronchial respiratory epithelial cell culture. Methods Mol Biol 2013;945:109–121.

    OpenUrlCrossRefPubMed
19. 19.↵
    1. Lanz E,
    2. Slavík J,
    3. Kotyk A

    . 2',7'-bis-(2-carboxyethyl)-5(6)-carboxyfluorescein as a dual-emission fluorescent indicator of intracellular pH suitable for argon laser confocal microscopy. Folia Microbiol (Praha) 1999;44(4):429–434.

    OpenUrlCrossRefPubMed
20. 20.↵
    1. Benjamin D,
    2. Robay D,
    3. Hindupur SK,
    4. Pohlmann J,
    5. Colombi M,
    6. El-Shemerly MY,
    7. et al

    . Dual inhibition of the lactate transporters MCT1 and MCT4 is synthetic lethal with metformin due to NAD+ depletion in cancer cells. Cell Rep 2018;25(11):3047–3058.e3044.

    OpenUrlCrossRef
21. 21.↵
    1. De La Rosa V,
    2. Bennett AL,
    3. Ramsey IS

    . Coupling between an electrostatic network and the Zn(2+) binding site modulates Hv1 activation. J Gen Physiol 2018;150(6):863–881.

    OpenUrlAbstract/FREE Full Text
22. 22.↵
    1. Kuch BA,
    2. Linssen R,
    3. Yoshikawa H,
    4. Smallwood CD,
    5. Davis MD

    . Local effects of two intravenous formulations of pulmonary vasodilators on airway epithelium. Respir Care 2020;65(10):1427–1432.

    OpenUrlAbstract/FREE Full Text
23. 23.↵
    1. Durinck S,
    2. Spellman PT,
    3. Birney E,
    4. Huber W

    . Mapping identifiers for the integration of genomic datasets with the R/Bioconductor package biomaRt. Nat Protoc 2009;4(8):1184–1191.

    OpenUrlCrossRefPubMedWeb of Science
24. 24.↵
    1. Yu G,
    2. Wang LG,
    3. Han Y,
    4. He QY

    . ClusterProfiler: an R package for comparing biological themes among gene clusters. OMICS 2012;16(5):284–287.

    OpenUrlCrossRefPubMedWeb of Science
25. 25.↵
    1. Douidar SM

    . Nebulized sodium bicarbonate in acute chlorine inhalation. Pediatr Emerg Care 1997;13(6):406–407.

    OpenUrlCrossRefPubMedWeb of Science
26. 26.↵
    1. Gomez CCS,
    2. Parazzi PLF,
    3. Clinckspoor KJ,
    4. Mauch RM,
    5. Pessine FBT,
    6. Levy CE,
    7. et al

    . Safety, tolerability, and effects of sodium bicarbonate inhalation in cystic fibrosis. Clin Drug Investig 2020;40(2):105–117.

    OpenUrlCrossRef
27. 27.↵
    1. Sims AC,
    2. Burkett SE,
    3. Yount B,
    4. Pickles RJ

    . SARS-CoV replication and pathogenesis in an in vitro model of the human conducting airway epithelium. Virus Res 2008;133(1):33–44.

    OpenUrlCrossRefPubMedWeb of Science
28. 28.↵
    1. Sims AC,
    2. Yount B,
    3. Burkett SE,
    4. Baric RS,
    5. Pickles RJ

    . SARS CoV replication and pathogenesis in human airway epithelial cultures. Adv Exp Med Biol 2006;581:535–538.

    OpenUrlPubMed
29. 29.↵
    1. Schoeffel RE,
    2. Anderson SD,
    3. Altounyan RE

    . Bronchial hyperreactivity in response to inhalation of ultrasonically nebulised solutions of distilled water and saline. Br Med J (Clin Res Ed) 1981;283(6302):1285–1287.

    OpenUrlAbstract/FREE Full Text