Roxadustat for SARS-CoV-2 Infection: Old Signaling Raised New Hopes

Alkazmi, Luay; Al-Kuraishy, Hayder M; Batiha, Gaber El‐Saber; Mostafa‐Hedeab, Gomaa; Waard, Michel De; Sabatier, Jean‐Marc; Kabrah, Saeed; Saad, Hebatallah M.; Al-Gareeb, Ali I; Simal-Gándara, Jesús

doi:10.1007/s40268-022-00397-0

Cited by 12 publications

(15 citation statements)

References 22 publications

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“…Thus, correction of cardiovascular risk factors by statins pharmacotherapy could be beneficial in the prevention of AD. However, the use of statins pharmacotherapy in patients with underlying cardiovascular complications but with normal cholesterol may associate with the development of cognitive impairment [ 56 , 57 ].…”

Section: Statins and Admentioning

confidence: 99%

Statins Use in Alzheimer Disease: Bane or Boon from Frantic Search and Narrative Review

et al. 2022

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Alzheimer’s disease (AD) was used to describe pre-senile dementia to differentiate it from senile dementia, which develops in the adult age group of more than 65 years. AD is characterized by the deposition of amyloid beta (Aβ) plaque and tau-neurofibrillary tangles (TNTs) in the brain. The neuropathological changes in AD are related to the deposition of amyloid plaques, neurofibrillary tangles, and progression of neuroinflammation, neuronal mitochondrial dysfunction, autophagy dysfunction, and cholinergic synaptic dysfunction. Statins are one of the main cornerstone drugs for the management of cardiovascular disorders regardless of dyslipidemia status. Increasing the use of statins, mainly in the elderly groups for primary and secondary prevention of cardiovascular diseases, may affect their cognitive functions. Extensive and prolonged use of statins may affect cognitive functions in healthy subjects and dementia patients. Statins-induced cognitive impairments in both patients and health providers had been reported according to the post-marketing survey. This survey depends mainly on sporadic cases, and no cognitive measures were used. Evidence from prospective and observational studies gives no robust conclusion regarding the beneficial or detrimental effects of statins on cognitive functions in AD patients. Therefore, this study is a narrative review aimed with evidences to the beneficial, detrimental, and neutral effects of statins on AD.

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Section: Statins and Admentioning

confidence: 99%

Statins Use in Alzheimer Disease: Bane or Boon from Frantic Search and Narrative Review

et al. 2022

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“…Notably, hyperinflammation caused by high circulating pro-inflammatory cytokines and chemokines in severe COVID-19 infections may disrupt placental barriers and favor VT of SARS-CoV2 infections [ 50 , 109 , 110 ].…”

Section: Discussionmentioning

confidence: 99%

Pregnancy and COVID-19: high or low risk of vertical transmission

et al. 2022

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Coronavirus disease 19 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome 2 (SARS-CoV-2). Throughout the pandemic, evidence on the effects of COVID-19 during pregnancy has been inadequate due to the limited number of studies published. Therefore, the objective of this systematic review was to evaluate current literature regarding the effects of COVID-19 during pregnancy and establish pregnancy outcomes and vertical and perinatal transmission during pregnancy. Multiple databases were searched, including Embase, Medline, Web of Science, Scopus, and Cochrane Central Register of Control Clinical Trials, using the following keywords: [Pregnancy] AND [COVID-19 OR SARS-CoV-2 OR nCoV-19] OR [Perinatal transmission, Vertical transmission (VT), Pregnancy complications], [Pregnancy] AND [Hyperinflammation OR Cytokine storm]. We excluded in vitro and experimental studies, but also ex-vivo and animal study methods. To exclude the risk of bias during data collection and interpretation, all included studies were peer-reviewed publications. This review is estimated to tabulate the study intervention characteristics and compare them against the planned groups for each synthesis. Our findings showed that pregnant women are commonly susceptible to respiratory viral infections and severe pneumonia due to physiological immune suppression and pregnancy-induced changes. VT of SARS-CoV-2 infection during pregnancy is associated with a great deal of controversy and conflict. However, there is still no robust clinical evidence of VT. Furthermore, the clinical presentation and management of COVID-19 during pregnancy are nearly identical to those of non-pregnant women. Finally, chloroquine and remdesivir are the only two drugs evaluated as adequate for the management of COVID-19 during pregnancy.

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“…Therefore, high CPK is linked with more severe complications in COVID‐19. A systematic review illustrated that rhabdomyolysis and skeletal muscle injury are common complications in severely affected COVID‐19 patient 173,174 . It has been shown that RyRs antagonist DTN reduces risk of skeletal muscle injury in rats by suppressing expression of TNF‐α with augmentation of IL‐10 175 .…”

Section: Role Of Ryanodine Receptors and Dantrolene In Covid‐19mentioning

confidence: 99%

“…A systematic review illustrated that rhabdomyolysis and skeletal muscle injury are common complications in severely affected COVID-19 patient. 173,174 It has been shown that RyRs antagonist DTN reduces risk of skeletal muscle injury in rats by suppressing expression of TNF-α with augmentation of IL-10. 175 Notably, DTN attenuates organophosphorus-induced skeletal muscle injury through inhibition of oxidative stress and related skeletal muscle Ca +2 overload and ischemic damage.…”

Section: Dantrolene and Musculoskeletal Disorders In Covid-19mentioning

confidence: 99%

Dantrolene and ryanodine receptors in COVID‐19: The daunting task and neglected warden

Alkazmi

Al-Kuraishy

Al-Gareeb

et al. 2023

Clin Exp Pharma Physio

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Dantrolene (DTN) is a ryanodine receptor (RyR) antagonist that inhibits Ca 2+ release from stores in the sarcoplasmic reticulum. DTN is mainly used in the management of malignant hyperthermia. RyRs are highly expressed in immune cells and are involved in different viral infections, including severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), because Ca 2+ is necessary for viral replication, maturation and release. DTN can inhibit the proliferation of SARS-CoV-2, indicating its potential role in reducing entry and pathogenesis of SARS-CoV-2. DTN may increase clearance of SARS-CoV-2 and promote coronavirus disease 2019 (COVID-19) recovery by shortening the period of infection. DTN inhibits N-methyl-D-aspartate (NMDA) mediated platelets aggregations and thrombosis. Therefore, DTN may inhibit thrombosis and coagulopathy in COVID-19 through suppression of platelet NMDA receptors. Moreover, DTN has a neuroprotective effect against SARS-CoV-2 infection-induced brain injury through modulation of NMDA receptors, which are involved in excitotoxicity, neuronal injury and the development of neuropsychiatric disorders. In conclusion, DTN by inhibiting RyRs may attenuate inflammatory disorders in SARS-CoV-2 infection and associated cardio-pulmonary complications. Therefore, DNT could be a promising drug therapy against COVID-19. Preclinical and clinical studies are warranted in this regards.

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Roxadustat for SARS-CoV-2 Infection: Old Signaling Raised New Hopes

Cited by 12 publications

References 22 publications

Statins Use in Alzheimer Disease: Bane or Boon from Frantic Search and Narrative Review

Statins Use in Alzheimer Disease: Bane or Boon from Frantic Search and Narrative Review

Pregnancy and COVID-19: high or low risk of vertical transmission

Dantrolene and ryanodine receptors in COVID‐19: The daunting task and neglected warden

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