COVID-19 and RAS: Unravelling an Unclear Relationship

D’Ardes, Damiano; Boccatonda, Andrea; Rossi, Ilaria; Guagnano, Maria Teresa; Santilli, Francesca; Cipollone, Francesco; Bucci, Marco

doi:10.3390/ijms21083003

Cited by 83 publications

(104 citation statements)

References 58 publications

(90 reference statements)

Supporting

Mentioning

101

Contrasting

Unclassified

Order By: Relevance

“…The discrepancy in disease duration observed between the data of our cohort and other studies on Asian patients [ 7 , 14 ], within the limits of comparing different populations, may be probably due to genetic and clinical differences of patients and to interindividual differences [ 22 , 23 ], while the hypothesis of relevant mutations in the virus appears unlikely.…”

Section: Discussioncontrasting

confidence: 99%

Duration of COVID-19: Data from an Italian Cohort and Potential Role for Steroids

et al. 2020

Self Cite

View full text Add to dashboard Cite

The diffusion of SARS-CoV-2, starting from China in December 2019, has led to a pandemic, reaching Italy in February 2020. Previous studies in Asia have shown that the median duration of SARS-CoV-2 viral shedding was approximately 12–20 days. We considered a cohort of patients recovered from COVID-19 showing that the median disease duration between onset and end of COVID-19 symptoms was 27.5 days (interquartile range (IQR): 17.0–33.2) and that the median duration between onset of symptoms and microbiological healing, defined by two consecutive negative nasopharyngeal swabs, was 38 days (IQR: 31.7–50.2). A longer duration of COVID-19 with delayed clinical healing (symptom-free) occurred in patients presenting at admission a lower PaO2/FiO2 ratio (p < 0.001), a more severe clinical presentation (p = 0.001) and a lower lymphocyte count (p = 0.035). Moreover, patients presenting at admission a lower PaO2/FiO2 ratio and more severe disease showed longer viral shedding (p = 0.031 and p = 0.032, respectively). In addition, patients treated with corticosteroids had delayed clinical healing (p = 0.013).

show abstract

Section: Discussioncontrasting

confidence: 99%

Duration of COVID-19: Data from an Italian Cohort and Potential Role for Steroids

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Growing evidence supports the role of ACE2 downregulation in COVID-19 pathophysiology and the possible contribution of RAS axes unbalance to COVID-19 natural history (D'Ardes et al, 2020;Gheblawi et al, 2020;Lanza et al, 2020;Verdecchia et al, 2020). It seems that the dynamics of ACE2 and SARS-CoV-2 infection relies on an apparent paradox that depends on the bioavailability of ACE2: either (1) the individual infected by the virus has enough reservoir of ACE2 to resist the depletion of the enzyme and still counteract the deleterious effects of reduced ACE2 levels and activity; or (2) individuals with a small reservoir of ACE2 will not be able to activate the anti-inflammatory axis of the RAS and consequently will suffer from an exacerbated activation of the classical pro-inflammatory arm.…”

Section: Ras Imbalance and Covid-19 Pathophysiologymentioning

confidence: 95%

Insights on SARS-CoV-2 Molecular Interactions With the Renin-Angiotensin System

Costa

Perez

Palmeira

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

The emergence of SARS-CoV-2/human/Wuhan/X1/2019, a virus belonging to the species Severe acute respiratory syndrome-related coronavirus, and the recognition of Coronavirus Disease 2019 (COVID-19) as a pandemic have highly increased the scientific research regarding the pathogenesis of COVID-19. The Renin Angiotensin System (RAS) seems to be involved in COVID-19 natural course, since studies suggest the membrane-bound Angiotensin-converting enzyme 2 (ACE2) works as SARS-CoV-2 cellular receptor. Besides the efforts of the scientific community to understand the virus' molecular interactions with human cells, few studies summarize what has been so far discovered about SARS-CoV-2 signaling mechanisms and its interactions with RAS molecules. This review aims to discuss possible SARS-CoV-2 intracellular signaling pathways, cell entry mechanism and the possible consequences of the interaction with RAS components, including Angiotensin II (Ang II), Angiotensin-(1-7) [Ang-(1-7)], Angiotensin-converting enzyme (ACE), ACE2, Angiotensin II receptor type-1 (AT1), and Mas Receptor. We also discuss ongoing clinical trials and treatment based on RAS cascade intervention. Data were obtained independently by the two authors who carried out a search in the PubMed, Embase, LILACS, Cochrane, Scopus, SciELO and the National Institute of Health databases using Medical Subject Heading terms as "SARS-CoV-2," "COVID-19," "Renin Angiotensin System," "ACE2," "Angiotensin II," "Angiotensin-(1-7)," and "AT1 receptor." Similarly to other members of Coronaviridae family, the molecular interactions between the pathogen and the membrane-bound ACE2 are based on the cleavage of the spike glycoprotein (S) in two subunits. Following the binding of the S1 receptor-binding domain (RBD) to ACE2, transmembrane protease/serine subfamily 2 (TMPRSS2) cleaves the S2 domain to facilitate membrane fusion. It is very likely that SARS-CoV-2 cell entry results in downregulation of membrane-bound ACE2, an enzyme that converts Ang II into Ang-(1-7). This mechanism can result in lung injury and vasoconstriction. In addition, Ang II activates pro-inflammatory cascades when binding to the AT1 Receptor. On the other

show abstract

“…In this study we have explored Urtica, which exhibits a range of bioactive compounds that can target ACE-2, an important enzyme of the RAS system and a decisive target for internalization of SARS CoV-2, thus docking of these compounds with ACE-2 will certainly serve to surmount the viral load. Most crucial molecules of the RAS system including ACE2 are present in the lungs therefore lungs are the most affected organ from this virus [24]. ACE, an enzyme present in the lung tissue converts angiotensin I to angiotensin II, which can either bind to AT1R or AT2R where it induces Vasconstriction or Vasodilation respectively [24].…”

Section: Discussionmentioning

confidence: 99%

“…Most crucial molecules of the RAS system including ACE2 are present in the lungs therefore lungs are the most affected organ from this virus [24]. ACE, an enzyme present in the lung tissue converts angiotensin I to angiotensin II, which can either bind to AT1R or AT2R where it induces Vasconstriction or Vasodilation respectively [24]. ACE2 another enzyme present in the lung tissue acts on Angiotensin II and converts it into Ang1-7 which in turn binds to the Mas-R leading to vasodilation [24].ACE-2 comes to the surface only when glycosylated, during SARS CoV-2 infection S (spike) protein of the virus binds to the ACE-2 receptors which result in the internalization of the virus further the viral genome is released into the cytosol where its replication and translation takes place to assemble newly formed virion which are later exocytosed (Fig.…”

Section: Discussionmentioning

confidence: 99%

Identification of novel inhibitors of Angiotensin-converting enzyme 2 (ACE-2) receptor from Urtica dioica to combat coronavirus disease 2019 (COVID-19)

Upreti

Prusty

Pandey

et al. 2020

Preprint

View full text Add to dashboard Cite

The pandemic outbreak of coronavirus (SARS-CoV-2) is rapidly spreading across the globe, so the development of anti-SARS-CoV-2 agents is urgently needed. Angiotensin-converting enzyme 2 (ACE-2), a human receptor that facilitates entry of SARS-CoV-2, serves as a prominent target for drug discovery. In the present study, we have applied the bioinformatics approach for screening of a series of bioactive chemical compounds from Himalayan stinging nettle (Urtica dioica) as potent inhibitors of ACE-2 receptor (PDB ID: 1R4L). The molecular docking was applied to dock a set of representative compounds within the active site region of target receptor protein using 0.8 version of the PyRx virtual screen tool and analyzed by using discovery studio visualizer. Based on the highest binding affinity, 16 compounds were shortlisted as a lead molecule using molecular docking analysis. Among them, β-sitosterol was found with the highest binding affinity -12.2 Kcal/mol and stable interactions with the amino acid residues present on the active site of the ACE-2 receptor. Similarly, Luteoxanthin and Violaxanthin followed by rutin also displayed stronger binding efficiency. We propose these compounds as potential lead candidates for the development of target specific therapeutic drugs against COVID-19.

show abstract

COVID-19 and RAS: Unravelling an Unclear Relationship

Cited by 83 publications

References 58 publications

Duration of COVID-19: Data from an Italian Cohort and Potential Role for Steroids

Duration of COVID-19: Data from an Italian Cohort and Potential Role for Steroids

Insights on SARS-CoV-2 Molecular Interactions With the Renin-Angiotensin System

Identification of novel inhibitors of Angiotensin-converting enzyme 2 (ACE-2) receptor from Urtica dioica to combat coronavirus disease 2019 (COVID-19)

Contact Info

Product

Resources

About