Sodium Bicarbonate Nebulized Therapy in Patients with Confirmed COVID-19

Abstract

To release their nucleocapsid into the cell, they rely on the binding to the cellular receptors, angiotensin converting enzyme 2 (ACE2) for SARS-CoV-2, by major conformational changes of the virus spike glycoprotein (S) and entry into the cells by endocytosis.1,2 The created endosome, where a slightly acidic environment is required for optimum fusion of its membrane and virus envelope, followed by the stages of fusion, uncoating and release of the genome into the host cell cytoplasm.3,4 The protonation of critical residues on a viral envelope glycoprotein alters its conformation and exposes a hydrophobic "fusion peptide" domain to facilitate the fusion.5 Infection of SARS-CoV-2 may be prevented by treatment of cells with inhibitors of endosome acidification. Sodium bicarbonate (NaHCO3), like endosomotropic weak bases ammonium chloride (NH4Cl), chloroquine (CLQ)/ hydroxychloroquine (CLQ-OH) as well as bafilomycin A (BAF), may raise the pH in vesicle/ endosomes and would be expected to inhibit nucleocapsid release of a SARS-CoV-2 which required an acidic endosomal environment for uncoating (as shown in the Figure 1).1,4,6,7 Therefore, inhalation of the nebulized sodium bicarbonate solution (<5%) by the patients with confirmed COVID-19, several times during the day, probably able to stop the fusion and uncoating stages. Yang ZY, Huang Y, Ganesh L, Leung K, Kong WP, Schwartz O, et al. pH-dependent entry of severe acute respiratory syndrome coronavirus is mediated by the spike glycoprotein and enhanced by dendritic cell transfer through DC-SIGN.

Dear Editor,

A global outbreak of severe acute respiratory syndrome (SARS) caused by a new coronavirus (CoV-2) began in December 2019. It induced a novel identified sickness named coronavirus disease 2019 (COVID-19). The rapid emergence of COVID-19 along with the considerable illness and mortality of the disease made it a major public health issue. Due to the lack of effective treatments, an extensive attempt is under way to provide and examine antiviral drugs.

Coronaviruses are enveloped positive-stranded RNA viruses that replicate in the host cell cytoplasm. To release their nucleocapsid into the cell, they rely on the binding to the cellular receptors, angiotensin converting enzyme 2 (ACE2) for SARS-CoV-2, by major conformational changes of the virus spike glycoprotein (S) and entry into the cells by endocytosis.1,2 The created endosome, where a slightly acidic environment is required for optimum fusion of its membrane and virus envelope, followed by the stages of fusion, uncoating and release of the genome into the host cell cytoplasm.3,4 The protonation of critical residues on a viral envelope glycoprotein alters its conformation and exposes a hydrophobic "fusion peptide" domain to facilitate the fusion.5 Infection of SARS-CoV-2 may be prevented by treatment of cells with inhibitors of endosome acidification.

Sodium bicarbonate (NaHCO3), like endosomotropic weak bases ammonium chloride (NH4Cl), chloroquine (CLQ)/ hydroxychloroquine (CLQ-OH) as well as bafilomycin A (BAF), may raise the pH in vesicle/ endosomes and would be expected to inhibit nucleocapsid release of a SARS-CoV-2 which required an acidic endosomal environment for uncoating (as shown in the Figure 1).1,4,6,7

Therefore, inhalation of the nebulized sodium bicarbonate solution (<5%) by the patients with confirmed COVID-19, several times during the day, probably able to stop the fusion and uncoating stages. In this case, the replication phase will also remain barren and eventually the respiratory infection will be controlled. Prospective controlled trials are needed to evaluate this method efficacy.

Ethical Issues

Not applicable.

Conflict of Interest

The authors declare that there is no conflict of interests.

References

References

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6. Yang ZY, Huang Y, Ganesh L, Leung K, Kong WP, Schwartz O, et al. pH-dependent entry of severe acute respiratory syndrome coronavirus is mediated by the spike glycoprotein and enhanced by dendritic cell transfer through DC-SIGN. J Virol 2004;78(11):5642-50. doi: 10.1128/jvi.78.11.5642-5650.2004

7. Fantini J, Di Scala C, Chahinian H, Yahi N. Structural and molecular modelling studies reveal a new mechanism of action of chloroquine and hydroxychloroquine against SARS-CoV-2 infection. Int J Antimicrob Agents 2020;55(5):105960. doi: 10.1016/j.ijantimicag.2020.105960