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Nanoantidote for repression of acidosis pH promoting COVID‐19 infection

Liu et al., VIEW, doi:10.1002/VIW.20220004

May 2022

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Alkalinization

28th treatment shown to reduce risk in November 2021, now with p = 0.0000000046 from 14 studies.

Lower risk for mortality, progression, recovery, and viral clearance.

No treatment is 100% effective. Protocols combine treatments.

5,100+ studies for 109 treatments. c19early.org

In Vitro study showing that acidosis-related low pH increases SARS-CoV-2 pseudovirus infection in HEK293T-ACE2 and human umbilical vein endothelial cells (HUVECs). Authors find that low pH of 6.8 (simulating acidosis in COVID-19 patients) increases ACE2 receptor levels on the cell membrane by reducing actin polymerization, compared to normal physiological pH of 7.4. The antacid nanoparticle CaCO3-NP neutralized the acidic pH and reduced ACE2 membrane levels and viral infection to normal pH 7.4 levels. Results suggest a positive feedback loop where SARS-CoV-2 infection induces acidosis, which further enhances viral entry and infection.

3 preclinical studies support the efficacy of alkalinization for COVID-19:

3 In Vitro studies1-3

Important missing comments or errors? Let us know.

1. Kreutzberger et al., SARS-CoV-2 requires acidic pH to infect cells, Proceedings of the National Academy of Sciences, doi:10.1073/pnas.2209514119.pnas.org, doi.org.

2. Liu et al., Nanoantidote for repression of acidosis pH promoting COVID‐19 infection, VIEW, doi:10.1002/VIW.20220004.wiley.com, doi.org.

3. Jimenez et al., Acid pH Increases SARS-CoV-2 Infection and the Risk of Death by COVID-19, Frontiers in Medicine, doi:10.3389/fmed.2021.637885.frontiersin.org, doi.org.

Liu et al., 31 May 2022, peer-reviewed, 7 authors. Contact: chengli_2017@tongji.edu.cn, lisiguang@tongji.edu.cn, wgcui80@hotmail.com.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

This Paper Alkalinization All

Nanoantidote for repression of acidosis pH promoting COVID‐19 infection

Qidong Liu, Huitong Ruan, Zhihao Sheng, Xiaoru Sun, Siguang Li, Wenguo Cui, Cheng Li

VIEW, doi:10.1002/viw.20220004

Acidosis, such as respiratory acidosis and metabolic acidosis, can be induced by coronavirus disease 2019 (COVID-19) infection and is associated with increased mortality in critically ill COVID-19 patients. It remains unclear whether acidosis further promotes SARS-CoV-2 infection in patients, making virus removal difficult. For antacid therapy, sodium bicarbonate poses great risks caused by sodium overload, bicarbonate side effects, and hypocalcemia. Therefore, new antacid antidote is urgently needed. Our study showed that an acidosis-related pH of 6.8 increases SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) expression on the cell membrane by regulating intracellular microfilament polymerization, promoting SARS-CoV-2 pseudovirus infection. Based on this, we synthesized polyglutamic acid-PEG materials, used complexation of calcium ions and carboxyl groups to form the core, and adopted biomineralization methods to form a calcium carbonate nanoparticles (CaCO 3 -NPs) nanoantidote to neutralize excess hydrogen ions (H + ), and restored the pH from 6.8 to approximately 7.4 (normal blood pH). CaCO 3 -NPs effectively prevented the heightened SARS-CoV-2 infection efficiency due to pH 6.8. Our study reveals that acidosis-related pH promotes SARS-CoV-2 infection, which suggests the existence of a positive feedback loop in which SARS-CoV-2 infection-induced acidosis enhances SARS-CoV-2 infection. Therefore, antacid therapy for acidosis COVID-19 patients is necessary. CaCO 3 -NPs may become an effective antacid nanoantidote superior to sodium bicarbonate.

C O N F L I C T O F I N T E R E S T The authors declare that there is no conflict of interest. O R C I D Zhihao Sheng https://orcid.org/0000-0002-6675-1400 R E F E R E N C E S

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