Heme oxygenase-1, carbon monoxide, and malaria – The interplay of chemistry and biology

Pena, Ana C.; Pamplona, Ana

doi:10.1016/j.ccr.2021.214285

Cited by 7 publications

(2 citation statements)

References 282 publications

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“…The anti-DENV effects of HO-1 are exerted through its enzymatic product, biliverdin, an inhibitor of DENV proteases (NS2B/NS3), and DENV protease-suppressed antiviral IFN response is thereby rescued [70,81,143]. In experimental models of severe malaria and HO-1 was shown to control resistance and susceptibility to cerebral malaria and malaria-associated acute lung injury while its pharmacological induction with cobalt protoporphyrin (CoPPIX) reduced experimental cerebral malaria incidence, and demonstrated significant delay in DENV disease onset and mortality, along with lower cerebral DENV load [143,144]. HO-1's cytoprotective, anti-inflammatory, and antiviral properties may aid in SARS-CoV-2 protection as its upregulation by the SARS-CoV-2 S protein has been documented in-vitro and some repurposed drugs reportedly protective against COVID-19, increase HO-1 [143,145,146].…”

Section: Mir-155 Engenders Sars-cov-2 Protection In Hemoglobin E (Hbe...mentioning

confidence: 99%

Beauty and the beast: host microRNA-155 versus SARS-CoV-2

Papadopoulos

Papadopoulou

2023

Human Cell

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Severe acute respiratory coronavirus 2 (SARS-CoV-2) infection in the young and healthy usually results in an asymptomatic or mild viral syndrome, possibly through an erythropoietin (EPO)-dependent, protective evolutionary landscape. In the old and in the presence of co-morbidities, however, a potentially lethal coronavirus disease 2019 (COVID-19) cytokine storm, through unrestrained renin-angiotensin aldosterone system (RAAS) hyperactivity, has been described. Multifunctional microRNA-155 (miR-155) elevation in malaria, dengue virus (DENV), the thalassemias, and SARS-CoV-1/2, plays critical antiviral and cardiovascular roles through its targeted translational repression of over 140 genes. In the present review, we propose a plausible miR-155-dependent mechanism whereby the translational repression of AGRT1 , Arginase-2 and Ets-1 , reshapes RAAS towards Angiotensin II (Ang II) type 2 (AT2R)-mediated balanced, tolerable, and SARS-CoV-2-protective cardiovascular phenotypes. In addition, it enhances EPO secretion and endothelial nitric oxide synthase activation and substrate availability, and negates proinflammatory Ang II effects. Disrupted miR-155 repression of AT1R + 1166C-allele, significantly associated with adverse cardiovascular and COVID-19 outcomes, manifests its decisive role in RAAS modulation. BACH1 and SOCS1 repression creates an anti-inflammatory and cytoprotective milieu, robustly inducing antiviral interferons. MiR-155 dysregulation in the elderly, and in comorbidities, allows unimpeded RAAS hyperactivity to progress towards a particularly aggressive COVID-19 course. Elevated miR-155 in thalassemia plausibly engenders a favorable cardiovascular profile and protection against malaria, DENV, and SARS-CoV-2. MiR-155 modulating pharmaceutical approaches could offer novel therapeutic options in COVID-19.

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Section: Mir-155 Engenders Sars-cov-2 Protection In Hemoglobin E (Hbe...mentioning

confidence: 99%

Beauty and the beast: host microRNA-155 versus SARS-CoV-2

Papadopoulos

Papadopoulou

2023

Human Cell

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“…As one of the three major gas signaling molecules, carbon monoxide (CO) plays an extremely important role in living organisms, 1,2 and CO in the human body is mainly derived from the process of catabolizing heme by heme oxygenase-1 (HO-1). [3][4][5] Previous studies have shown that CO, as a potential therapeutic drug, plays an important role in antihypertensive, antiinflammatory, and anti-proliferative therapies. [6][7][8][9] When its metabolic level is abnormal, it is related to the occurrence and development of Alzheimer's disease, cardiovascular disease, lung disease, and other diseases.…”

Section: Introductionmentioning

confidence: 99%