Do angiotensin II type 1 receptor blockers have molecular effects?

Miura, Shin-ichiro; Saku, Keijiro

doi:10.1038/hr.2009.202

Cited by 8 publications

(5 citation statements)

References 25 publications

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“…It is a useful therapeutic choice in the management of patients suffering from hypertension. (Miura et al., 2011 ). Phaitanthrin D showed (-7.9 Kcal/mol) binding energy with Nsp9 replicase and interacted with the 6W4B.…”

Section: Resultsmentioning

confidence: 99%

Structure-based drug repurposing for targeting Nsp9 replicase and spike proteins of severe acute respiratory syndrome coronavirus 2

Chandel

Sharma

Raj

et al. 2020

Journal of Biomolecular Structure and Dynamics

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Drug re-purposing might be a fast and efficient way of drug development against the novel coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We applied a bioinformatics approach using molecular dynamics and docking to identify FDA-approved drugs that can be re-purposed to potentially inhibit the non-structural protein 9 (Nsp9) replicase and spike proteins in SARS-CoV-2. We performed virtual screening of FDA-approved compounds, including antiviral, anti-malarial, anti-parasitic, anti-fungal, anti-tuberculosis, and active phytochemicals against the Nsp9 replicase and spike proteins. Selected hit compounds were identified based on their highest binding energy and favorable absorption, distribution, metabolism and excretion (ADME) profile. Conivaptan, an arginine vasopressin antagonist drug exhibited the highest binding energy (-8.4 Kcal/ mol) and maximum stability with the amino acid residues present at the active site of the Nsp9 replicase. Tegobuvir, a non-nucleoside inhibitor of the hepatitis C virus, also exhibited maximum stability along with the highest binding energy (-8.1 Kcal/mol) at the active site of the spike proteins. Molecular docking scores were further validated by molecular dynamics using Schrodinger, which supported the strong stability of ligands with the proteins at their active sites through water bridges, hydrophobic interactions, and H-bonding. Our findings suggest Conivaptan and Tegobuvir as potential therapeutic agents against SARS-CoV-2. Further in vitro and in vivo validation and evaluation are warranted to establish how these drug compounds target the Nsp9 replicase and spike proteins.

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Section: Resultsmentioning

confidence: 99%

Structure-based drug repurposing for targeting Nsp9 replicase and spike proteins of severe acute respiratory syndrome coronavirus 2

Chandel

Sharma

Raj

et al. 2020

Journal of Biomolecular Structure and Dynamics

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“…Small differences in the molecular structure of each ARB have demonstrated unique molecular effects in experimental studies. Thus, some benefi ts conferred by ARBs beyond blood pressure control may not be class effects but rather molecular effects as shown in some experimental studies [ 143 ]. Some of these effects may account for differences in clinical outcome as shown in Table 36.1 under the column "indication.…”

Section: Mechanism Of Actionmentioning

confidence: 91%

Drugs Targeting RAAS in the Treatment of Hypertension and Other Cardiovascular Diseases

Balakumar

Jagadeesh

2015

Pathophysiology and Pharmacotherapy of Cardiovascular Disease

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Drugs with diversifi ed structure and class target the RAAS cascade at various levels. Beginning with the inhibition of renin from the juxtaglomerular cells of the kidney, it extends to the blockade of formation and actions of its principal component, Ang II, and its effector, aldosterone and its synthesis. Although all of them are very effi cacious in combating overactivation of RAAS, ACE inhibitors and ARBs stand out in the armamentarium of RAAS inhibitors. All of them are effective in lowering blood pressure but differ from each other in potency, pharmacokinetic properties and additional pharmacologic actions that are contributed by their unique functional groups. Therapeutic uses of RAAS blockers stem from the dynamics of the complex intertwined downstream signaling molecules that interact to contribute beyond blood pressure control. Thus, some of the ACE inhibitors and ARBs are also indicated in the treatment of heart failure, left ventricular dysfunction following myocardial infarction, and nephropathy in T2DM, reducing the risk of cardiovascular mortality, nonfatal myocardial infarction, and the risk of developing heart failure. Several studies have investigated the dual inhibition of the RAAS in hypertension and heart failure with an outcome of more adverse events without an increase in benefi t. While considering Ang II and aldosterone escape processes during ACE inhibitors and ARBs therapies, RAAS at the base level can be halted using aldosterone receptor antagonists for the management of hypertension and heart failure. InThe opinions expressed herein are those of GJ and do not necessarily refl ect those of the US Food and Drug Administration.

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“…ARBs, including azilsartan, candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, and valsartan, are Ang II antagonists that bind to and inhibit AT1R [108]. Although the blockers suppress the AT1R pathway, in this condition, Ang II is free to stimulate further AT2R, which causes vasodilation and normalizes blood pressure.…”

Section: Ras Therapeutic Interventions Used In Diabetic Nephropathymentioning

confidence: 99%

Molecular Mechanisms Involved in Intrarenal Renin-Angiotensin and Alternative Pathways in Diabetic Nephropathy - A Review

Bahreini¹,

Rezaei-Chianeh²,

Nabi‐Afjadi³

2021

Review of Diabetic Studies

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Do angiotensin II type 1 receptor blockers have molecular effects?

Cited by 8 publications

References 25 publications

Structure-based drug repurposing for targeting Nsp9 replicase and spike proteins of severe acute respiratory syndrome coronavirus 2

Structure-based drug repurposing for targeting Nsp9 replicase and spike proteins of severe acute respiratory syndrome coronavirus 2

Drugs Targeting RAAS in the Treatment of Hypertension and Other Cardiovascular Diseases

Molecular Mechanisms Involved in Intrarenal Renin-Angiotensin and Alternative Pathways in Diabetic Nephropathy - A Review

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