The Potential Role of Lithium as an Antiviral Agent against SARS-CoV-2 via Membrane Depolarization: Review and Hypothesis

Qaswal, Abdallah Barjas; Suleiman, Aiman; Guzu, Hasan; Harb, T.; Atiyat, Bashir

doi:10.3390/scipharm89010011

Cited by 13 publications

(15 citation statements)

References 81 publications

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“…Lithium has even been proposed as a candidate treatment for COVID-19. It can suppress NOD-like receptor family pyrin domain containing-3 (NLRP3) inflammasome activity (which is implicated in the release of pro-inflammatory cytokines during the cytokine storm), inhibits cell death (resulting in a decrease in lung parenchymal damage), and is characterized by immune-regulatory mechanisms (preventing the harmful effects of immune hyperactivation) ( 94 ). However, its antiviral properties, as well as its safety as a potential antiviral agent (due to its narrow therapeutic index and high risk of toxicity), remain to be confirmed in clinical settings ( 93 , 95 ).…”

Section: Discussionmentioning

confidence: 99%

COVID-19-Related Mortality Risk in People With Severe Mental Illness: A Systematic and Critical Review

et al. 2022

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Background: Increasing clinical evidence suggests that people with severe mental illness (SMI), including schizophrenia spectrum disorders, bipolar disorder (BD), and major depressive disorder (MDD), are at higher risk of dying from COVID-19. Several systematic reviews examining the association between psychiatric disorders and COVID-19-related mortality have recently been published. Although these reviews have been conducted thoroughly, certain methodological limitations may hinder the accuracy of their research findings.Methods: A systematic literature search, using the PubMed, Embase, Web of Science, and Scopus databases (from inception to July 23, 2021), was conducted for observational studies assessing the risk of death associated with COVID-19 infection in adult patients with pre-existing schizophrenia spectrum disorders, BD, or MDD. Methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS).Results: Of 1,446 records screened, 13 articles investigating the rates of death in patients with pre-existing SMI were included in this systematic review. Quality assessment scores of the included studies ranged from moderate to high. Most results seem to indicate that patients with SMI, particularly patients with schizophrenia spectrum disorders, are at significantly higher risk of COVID-19-related mortality, as compared to patients without SMI. However, the extent of the variation in COVID-19-related mortality rates between studies including people with schizophrenia spectrum disorders was large because of a low level of precision of the estimated mortality outcome(s) in certain studies. Most studies on MDD and BD did not include specific information on the mood state or disease severity of patients. Due to a lack of data, it remains unknown to what extent patients with BD are at increased risk of COVID-19-related mortality. A variety of factors are likely to contribute to the increased mortality risk of COVID-19 in these patients. These include male sex, older age, somatic comorbidities (particularly cardiovascular diseases), as well as disease-specific characteristics.Conclusion: Methodological limitations hamper the accuracy of COVID-19-related mortality estimates for the main categories of SMIs. Nevertheless, evidence suggests that SMI is associated with excess COVID-19 mortality. Policy makers therefore must consider these vulnerable individuals as a high-risk group that should be given particular attention. This means that targeted interventions to maximize vaccination uptake among these patients are required to address the higher burden of COVID-19 infection in this already disadvantaged group.

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Section: Discussionmentioning

confidence: 99%

COVID-19-Related Mortality Risk in People With Severe Mental Illness: A Systematic and Critical Review

et al. 2022

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“…Inhibition of cell death and neuron growth promotion are the neuroprotective properties of lithium, which occurs due to membrane depolarization. Are a result of membrane depolarization, lithium is very effective in BD treatment [247] . The effects of lithium on the body of patients are beyond mental problems and depression.…”

Section: Lithiummentioning

confidence: 99%

Molecular mechanisms and therapeutic effects of different vitamins and minerals in COVID-19 patients

Fath

Naderi

Hamzavi

et al. 2022

Journal of Trace Elements in Medicine and Biology

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“…The model of quantum tunneling of ions has been studied previously in hypothetical biological frameworks and was found to generate solid mathematical solutions on atomic and molecular levels in nascent fields of neurophysiology and pharmacokinetics [ 9 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

GABA Receptors Can Depolarize the Neuronal Membrane Potential via Quantum Tunneling of Chloride Ions: A Quantum Mathematical Study

Nawafleh

Qaswal

Suleiman

et al. 2022

Cells

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GABA (gamma-aminobutyric acid) receptors represent the major inhibitory receptors in the nervous system and their inhibitory effects are mediated by the influx of chloride ions that tends to hyperpolarize the resting membrane potential. However, GABA receptors can depolarize the resting membrane potential and thus can also show excitatory effects in neurons. The major mechanism behind this depolarization is mainly attributed to the accumulation of chloride ions in the intracellular compartment. This accumulation leads to increase in the intracellular chloride concentration and depolarize the Nernst potential of chloride ions. When the membrane potential is relatively hyperpolarized, this will result in a chloride efflux instead of influx trying to reach their depolarized equilibrium potential. Here, we propose different mechanism based on a major consequence of quantum mechanics, which is quantum tunneling. The quantum tunneling model of ions is applied on GABA receptors and their corresponding chloride ions to show how chloride ions can depolarize the resting membrane potential. The quantum model states that intracellular chloride ions have higher quantum tunneling probability than extracellular chloride ions. This is attributed to the discrepancy in the kinetic energy between them. At physiological parameters, the quantum tunneling is negligible to the degree that chloride ions cannot depolarize the membrane potential. Under certain conditions such as early neuronal development, gain-of-function mutations, stroke and trauma that can lower the energy barrier of the closed gate of GABA receptors, the quantum tunneling is enhanced so that the chloride ions can depolarize the resting membrane potential. The major unique feature of the quantum tunneling mechanism is that the net efflux of chloride ions is attained without the need for intracellular accumulation of chloride ions as long as the energy barrier of the gate is reduced but still higher than the kinetic energy of the chloride ion as a condition for quantum tunneling to take place.

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The Potential Role of Lithium as an Antiviral Agent against SARS-CoV-2 via Membrane Depolarization: Review and Hypothesis

Cited by 13 publications

References 81 publications

COVID-19-Related Mortality Risk in People With Severe Mental Illness: A Systematic and Critical Review

COVID-19-Related Mortality Risk in People With Severe Mental Illness: A Systematic and Critical Review

Molecular mechanisms and therapeutic effects of different vitamins and minerals in COVID-19 patients

GABA Receptors Can Depolarize the Neuronal Membrane Potential via Quantum Tunneling of Chloride Ions: A Quantum Mathematical Study

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