Is GSK3β a molecular target of chloroquine treatment against COVID-19?

Embi, Mohammed Noor; Ganesan, N; Sidek, Hasidah Mohd

doi:10.5582/ddt.2020.03010

Cited by 11 publications

(4 citation statements)

References 6 publications

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“…Studies conducted on animal models of melioidosis suggest that the anti-inflammatory property of chloroquine is mediated by the inhibition of glycogen synthase kinase-3β. 151 Before the large-scale recommendation of off-label use, the potential of chloroquine to cause detrimental cardiac effects must be considered. 152 Currently a randomized controlled trial has been registered to evaluate the prophylactic potential of hydroxychloroquine in preventing secondary infections and severe clinical symptoms among individuals who came into contact with SARS-CoV-2 infected individuals.…”

Section: Non-antiviral Drugs Against Sars-cov-2 Infection: Old Dog Nementioning

confidence: 99%

Antivirals for COVID-19: A critical review

Frediansyah

Tiwari

Sharun

et al. 2021

Clinical Epidemiology and Global Health

156

144

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No specific drugs have been approved for coronavirus disease 2019 (COVID-19) to date as the development of antivirals usually requires time. Therefore, assessment and use of currently available antiviral drugs is critical for a timely response to the current pandemic. Here, we have reviewed anti-SARS-CoV-2 potencies of available antiviral drug groups such as fusion inhibitors, protease inhibitors, neuraminidase inhibitors, and M2 ion-channel protein blockers. Although clinical trials to assess the efficacy of these antivirals are ongoing, this review highlights important information including docking and modeling analyses, in vitro studies, as well as results from clinical uses of these antivirals against COVID-19 pandemic.

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Section: Non-antiviral Drugs Against Sars-cov-2 Infection: Old Dog Nementioning

confidence: 99%

Antivirals for COVID-19: A critical review

Frediansyah

Tiwari

Sharun

et al. 2021

Clinical Epidemiology and Global Health

156

144

View full text Add to dashboard Cite

show abstract

“…Furthermore, lithium appears to inhibit the process by which IL‐6 activates the transcription factor STAT‐3 in an animal model of joint inflammation (Minashima, Zhang, Lee, & Kirsch, 2014), which means that it could potentially interrupt the self‐reinforcing inflammatory cascade described above. At least some of these effects appear to be related to the inhibitory effects of lithium on the enzyme glycogen synthase kinase‐3‐beta (GSK‐3β) (Beurel, Michalek, & Jope, 2010; Wang et al, 2013), which has also been identified as a molecular target for the action of chloroquine and hydroxychloroquine in reducing inflammation triggered by SARS‐nCoV‐2 (Embi, Ganesan, & Sidek, 2020). Besides its effects on this particular pathway, lithium also seems to have more widespread anti‐inflammatory effects, including the inhibition of interleukin‐1 beta (IL‐1β) production and the reduction of cyclooxygenase‐2 expression (Nassar & Azab, 2014).…”

Section: Action Mechanism Referencesmentioning

confidence: 99%

Lithium as a candidate treatment for COVID‐19: Promises and pitfalls

Rajkumar

2020

Drug Development Research

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The pandemic of respiratory illness caused by a novel coronavirus (SARS‐nCoV‐2) is a global health crisis. Despite numerous preliminary results, there is as yet no treatment of proven efficacy for this condition. In this context, the pharmacological properties of lithium, better known as a treatment for mood disorders, merit closer examination. Lithium has shown in vitro efficacy at inhibiting the replication of coronaviruses responsible for gastrointestinal and respiratory diseases in animals. It has immunomodulatory properties that may be of additional benefit in moderating the host inflammatory response to the novel coronavirus (SARS‐CoV‐2). Furthermore, there is evidence that lithium may exert a protective action against upper respiratory infections and influenza‐like illnesses in patients taking it for other indications. These promising reports must be balanced against the narrow therapeutic index and high risk of toxicity associated with lithium therapy, its documented interactions with several commonly used drugs, and the absence of evidence of its efficacy against coronaviruses responsible for human disease. Nevertheless, naturalistic studies of the risk of COVID‐19 in patients already receiving lithium could provide indirect evidence of its efficacy, and understanding the putative antiviral and immune‐regulatory mechanisms of lithium in models of SARS‐CoV‐2 infection may provide leads for the development of safer and more effective treatments with a specific action against COVID‐19.

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“…In addition to the direct effect of chloroquine on reducing the viral replication (10), in vitro studies demonstrated its inhibitory effect on the production of cytokines from leukocytes (7,11). Regarding the mechanisms of such anti-inflammatory properties of chloroquine, recent reports suggest the involvement of glycogen synthase kinase-3β (GSK3β) or Toll-like receptors (TLRs) (12,13). In our previous patch-clamp studies using murine thymocytes, both chloroquine and azithromycin strongly suppressed the activity of lymphocyte Kv1.3-channels and thus reduced the production of inflammatory cytokines (14,15).…”

Section: Coronavirus Disease 2019 (Covid-19mentioning

confidence: 90%

Targeting lymphocyte Kv1.3-channels to suppress cytokine storm in severe COVID-19: Can it be a novel therapeutic strategy?

Kazama

2020

DD&T

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cytokine storm, lymphocyte, chloroquine In the midst of a pandemic, finding effective treatments for coronavirus disease 2019 (COVID-19) is the urgent issue. In "chronic inflammatory diseases", the overexpression of delayed rectifier K + -channels (Kv1.3) in leukocytes is responsible for the overactivation of cellular immunity and the subsequent cytokine storm. In our previous basic studies, drugs including chloroquine and azithromycin strongly suppressed the channel activity and pro-inflammatory cytokine production from lymphocytes. These findings suggest a novel pharmacological mechanism by which chloroquine, with or without azithromycin, is effective for severe cases of COVID-19, in which the overactivation of cellular immunity and the subsequent cytokine storm are responsible for the pathogenesis.

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Is GSK3β a molecular target of chloroquine treatment against COVID-19?

Cited by 11 publications

References 6 publications

Antivirals for COVID-19: A critical review

Antivirals for COVID-19: A critical review

Lithium as a candidate treatment for COVID‐19: Promises and pitfalls

Targeting lymphocyte Kv1.3-channels to suppress cytokine storm in severe COVID-19: Can it be a novel therapeutic strategy?

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