Signaling via dopamine and adenosine receptors modulate viral peptide-specific and T-cell IL-8 response in COVID-19

Tokano, Mieko; Takagi, Ryukichi; Kawano, Masaaki; Maesaki, Shigefumi; Tarumoto, Norihito; Matsushita, Sho

doi:10.1080/25785826.2022.2079369

Cited by 6 publications

(2 citation statements)

References 17 publications

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“…Remdesivir is a prodrug, and its metabolites are adenosine analogues with a longer half-life than adenosine ( 19 ), which might have a number of off-target effects. Adenosine may exert chronotropic effects on the heart ( 20 ) and modify immune response ( 21 , 22 ). Besides kidney and hepatic toxicities ( 23 ), remdesivir use in COVID-19 patients has been associated with development of bradycardia ( 24 , 25 ), repolarization abnormalities ( 26 ), and a higher frequency of bacteremia ( 27 ), all of which are phenomena with uncertain mechanisms and various prognostic impact on the affected patients.…”

Section: Discussionmentioning

confidence: 99%

Real-life experience with remdesivir for treatment of hospitalized coronavirus disease 2019 patients: matched case-control study from a large tertiary hospital registry

et al. 2022

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Aim To evaluate the association of remdesivir use and the survival of hospitalized patients with coronavirus disease 2019 (COVID-19). Methods We retrospectively reviewed the medical records of 5959 COVID-19 patients admitted to our tertiary-level hospital from March 2020 to June 2021. A total of 876 remdesivir-treated patients were matched with 876 control patients in terms of age, sex, Charlson comorbidity index (CCI), WHO-defined COVID-19 severity on admission, and oxygen requirement at the time of remdesivir use. Results Among 1752 COVID-19 patients (median age 66 years, 61.8% men), 1405 (80.2%) had severe and 311 (17.8%) had critically severe COVID-19 on admission. Remdesivir was given at a median of one day after hospital admission and at a median of eight days from the onset of symptoms. Overall, 645 (73.6%) patients received remdesivir before high-flow oxygen therapy (HFOT) or mechanical ventilation (MV), 198 (22.6%) after HFOT institution, and 83 (9.5%) after MV institution. Remdesivir use was associated with improved survival in the entire cohort (hazard ratio 0.79, P = 0.006). Survival benefit was evident among patients receiving remdesivir during low-flow oxygen requirement (hazard ratio 0.61, P < 0.001) but not among patients who received it after starting HFOT ( P = 0.499) or MV ( P = 0.380). Conclusion Remdesivir, if given during low-flow oxygen therapy, might be associated with survival benefit in hospitalized COVID-19 patients.

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Section: Discussionmentioning

confidence: 99%

Real-life experience with remdesivir for treatment of hospitalized coronavirus disease 2019 patients: matched case-control study from a large tertiary hospital registry

et al. 2022

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“…Tokano et al [14] analysed the modulation of the A2A receptor with istradefylline in two preclinical studies (Table 1). Istradefylline is a selective A2A receptor antagonist indicated as an adjunct to levodopa and carbidopa for the treatment of Parkinson's disease.…”

Section: P1 Receptors In Covid-19mentioning

confidence: 99%

A Systematic Review of the Role of Purinergic Signalling Pathway in the Treatment of COVID-19

Korb

Schultz

Beckenkamp

et al. 2023

IJMS

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The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global health concern. Three years since its origin, despite the approval of vaccines and specific treatments against this new coronavirus, there are still high rates of infection, hospitalization, and mortality in some countries. COVID-19 is characterised by a high inflammatory state and coagulation disturbances that may be linked to purinergic signalling molecules such as adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine (ADO), and purinergic receptors (P1 and P2). These nucleotides/nucleosides play important roles in cellular processes, such as immunomodulation, blood clot formation, and vasodilation, which are affected during SARS-CoV-2 infection. Therefore, drugs targeting this purinergic pathway, currently used for other pathologies, are being evaluated in preclinical and clinical trials for COVID-19. In this review, we focus on the potential of these drugs to control the release, degradation, and reuptake of these extracellular nucleotides and nucleosides to treat COVID-19. Drugs targeting the P1 receptors could have therapeutic efficacy due to their capacity to modulate the cytokine storm and the immune response. Those acting in P2X7, which is linked to NLRP3 inflammasome activation, are also valuable candidates as they can reduce the release of pro-inflammatory cytokines. However, according to the available preclinical and clinical data, the most promising medications to be used for COVID-19 treatment are those that modulate platelets behaviour and blood coagulation factors, mainly through the P2Y12 receptor.

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Purinergic signaling: decoding its role in COVID-19 pathogenesis and promising treatment strategies

Shafaghat,

Ghomi,

Khorramdelazad

et al. 2023

Inflammopharmacol

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Signaling via dopamine and adenosine receptors modulate viral peptide-specific and T-cell IL-8 response in COVID-19

Cited by 6 publications

References 17 publications

Real-life experience with remdesivir for treatment of hospitalized coronavirus disease 2019 patients: matched case-control study from a large tertiary hospital registry

Real-life experience with remdesivir for treatment of hospitalized coronavirus disease 2019 patients: matched case-control study from a large tertiary hospital registry

A Systematic Review of the Role of Purinergic Signalling Pathway in the Treatment of COVID-19

Purinergic signaling: decoding its role in COVID-19 pathogenesis and promising treatment strategies

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