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1.
Front Pharmacol ; 12: 603736, 2021.
Article in English | MEDLINE | ID: covidwho-1186854

ABSTRACT

COVID-19 pandemic demands a swift response to find therapeutic tools that effectively reduce morbidity and mortality. Despite initial fears, evidence from retrospective observational studies supports the inhibition of the renin-angiotensin system as an emerging pathway to delay or moderate angiotensin II-driven lung inflammation. This has triggered several prospective clinical trials. In this commentary we provide an overview and analysis of current ongoing clinical trials aimed at evaluating the therapeutic efficacy of angiotensin receptor blocker (ARB) use in COVID-19. The relevance of the results of these trials will have to be interpreted depending on the stage and severity of the disease and in light of the start time of their prescription related to the time of diagnosis of COVID-19 as well as the administered doses.

2.
Drug Dev Res ; 81(7): 768-770, 2020 11.
Article in English | MEDLINE | ID: covidwho-155438

ABSTRACT

In late 2019, a new coronavirus emerged in Wuhan Province, China, causing lung complications similar to those produced by the SARS coronavirus in the 2002-2003 epidemic. This new disease was named COVID-19 and the causative virus SARS-CoV-2. The SARS-CoV-2 virus enters the airway and binds, by means of the S protein on its surface to the membrane protein ACE2 in type 2 alveolar cells. The S protein-ACE2 complex is internalized by endocytosis leading to a partial decrease or total loss of the enzymatic function ACE2 in the alveolar cells and in turn increasing the tissue concentration of pro-inflammatory angiotensin II by decreasing its degradation and reducing the concentration of its physiological antagonist angiotensin 1-7. High levels of angiotensin II on the lung interstitium can promote apoptosis initiating an inflammatory process with release of proinflammatory cytokines, establishing a self-powered cascade, leading eventually to ARDS. Recently, Gurwitz proposed the tentative use of agents such as losartan and telmisartan as alternative options for treating COVID-19 patients prior to development of ARDS. In this commentary article, the authors make the case for the election of telmisartan as such alternative on the basis of its pharmacokinetic and pharmacodynamic properties and present an open-label randomized phase II clinical trial for the evaluation of telmisartan in COVID-19 patients (NCT04355936).


Subject(s)
Angiotensin II Type 1 Receptor Blockers/therapeutic use , COVID-19/drug therapy , SARS-CoV-2/physiology , Telmisartan/therapeutic use , Angiotensin II Type 1 Receptor Blockers/pharmacology , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/metabolism , Clinical Trials, Phase II as Topic , Humans , Lung/metabolism , Lung/virology , Pandemics , Protein Binding/drug effects , SARS-CoV-2/drug effects , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Telmisartan/pharmacology , Virus Internalization/drug effects
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