Potential inhibitors of the interaction between ACE2 and SARS-CoV-2 (RBD), to develop a drug

Benítez‐Cardoza, Claudia G.; Vique‐Sánchez, José Luis

doi:10.1016/j.lfs.2020.117970

Cited by 46 publications

(56 citation statements)

References 41 publications

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“…In Figure S5 and Figure 6A , the crystal structure of spike protein-ACE2 (PDB: 6M17) revealed that the aminoacid residues of ACE2, including Gln24, Thr27, Asp30, Lys31, His34, Glu35, Glu37, Asp38, Tyr41, Gln42, Met82, Lys353, Gly354, Asp355, and Arg357, were recognized as the Spike protein receptor-binding domain (RBD) or entry receptor site to invade the target cells (Benítez-Cardoza and Vique-Sánchez, 2020 ). Based on the virtual screening results of ACE2 protein, CP-609754, saquinavir, rilapladib, quarfloxin, batefenterol, oxolinic acid, alatrofloxacin, dovitinib, GSK-256066, and rebamipide were predicted as the best compounds, exhibiting a high binding affinity to ACE2 with low energy ( Figure 5 and Table S4 ).…”

Section: Resultsmentioning

confidence: 99%

Quinolines-Based SARS-CoV-2 3CLpro and RdRp Inhibitors and Spike-RBD-ACE2 Inhibitor for Drug-Repurposing Against COVID-19: An in silico Analysis

et al. 2020

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The novel coronavirus SARS-CoV-2 disease "COVID-19" emerged in China and rapidly spread to other countries; due to its rapid worldwide spread, the WHO has declared this as a global emergency. As there is no specific treatment prescribed to treat COVID-19, the seeking of suitable therapeutics among existing drugs seems valuable. The structure availability of coronavirus macromolecules has encouraged the finding of conceivable anti-SARS-CoV-2 therapeutics through in silico analysis. The results reveal that quinoline,1,2,3,4-tetrahydro-1-[(2-phenylcyclopropyl)sulfonyl]-trans-(8CI) and saquinavir strongly interact with the active site (Cys-His catalytic dyad), thereby are predicted to hinder the activity of SARS-CoV-2 3CLpro. Out of 113 quinoline-drugs, elvitegravir and oxolinic acid are able to interact with the NTP entry-channel and thus interfere with the RNA-directed 5 ′-3 ′ polymerase activity of SARS-CoV-2 RdRp. The bioactivity-prediction results also validate the outcome of the docking study. Moreover, as SARS-CoV-2 Spike-glycoprotein uses human ACE2-receptor for viral entry, targeting the Spike-RBD-ACE2 has been viewed as a promising strategy to control the infection. The result shows rilapladib is the only quinoline that can interrupt the Spike-RBD-ACE2 complex. In conclusion, owing to their ability to target functional macromolecules of SARS-CoV-2, along with positive ADMET properties, quinoline,1,2,3,4-tetrahydro-1-[(2-phenylcyclopropyl)sulfonyl]-trans-(8CI), saquinavir, elvitegravir, oxolinic acid, and rilapladib are suggested for the treatment of COVID-19.

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Section: Resultsmentioning

confidence: 99%

Quinolines-Based SARS-CoV-2 3CLpro and RdRp Inhibitors and Spike-RBD-ACE2 Inhibitor for Drug-Repurposing Against COVID-19: An in silico Analysis

et al. 2020

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“…Therefore, the surface of the RBM interacts over a significant surface area on the ACE2. This provides two options for the inhibition of SARS-CoV-2 binding to the ACE2: (a) designing small molecule inhibitors that bind to the S1-RBM and inhibit the interaction with the ACE2 [197,198], and (b) use the ACE2 residues that interact with the S1-RBM as the target for the drug binding and inhibit the interaction with the SARS-CoV-2 ( Figure 4).…”

Section: Targeting Ace2 Binding Interfacementioning

confidence: 99%

ACE2: from protection of liver disease to propagation of COVID-19

et al. 2020

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Twenty years ago, the discovery of angiotensin-converting enzyme 2 (ACE2) was an important breakthrough dramatically enhancing our understanding of the renin–angiotensin system (RAS). The classical RAS is driven by its key enzyme ACE and is pivotal in the regulation of blood pressure and fluid homeostasis. More recently, it has been recognised that the protective RAS regulated by ACE2 counterbalances many of the deleterious effects of the classical RAS. Studies in murine models demonstrated that manipulating the protective RAS can dramatically alter many diseases including liver disease. Liver-specific overexpression of ACE2 in mice with liver fibrosis has proved to be highly effective in antagonising liver injury and fibrosis progression. Importantly, despite its highly protective role in disease pathogenesis, ACE2 is hijacked by SARS-CoV-2 as a cellular receptor to gain entry to alveolar epithelial cells, causing COVID-19, a severe respiratory disease in humans. COVID-19 is frequently life-threatening especially in elderly or people with other medical conditions. As an unprecedented number of COVID-19 patients have been affected globally, there is an urgent need to discover novel therapeutics targeting the interaction between the SARS-CoV-2 spike protein and ACE2. Understanding the role of ACE2 in physiology, pathobiology and as a cellular receptor for SARS-CoV-2 infection provides insight into potential new therapeutic strategies aiming to prevent SARS-CoV-2 infection related tissue injury. This review outlines the role of the RAS with a strong focus on ACE2-driven protective RAS in liver disease and provides therapeutic approaches to develop strategies to prevent SARS-CoV-2 infection in humans.

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“…Also, there are reports regarding small molecules against crucial protein targets that are essential for viral replication with proven potency. Recently, there are several reports cited on designing drugs for SARS-CoV-2 employing in silico virtual screening methods [ [5] , [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] ].…”

Section: Introductionmentioning

confidence: 99%

Structure-based drug designing towards the identification of potential anti-viral for COVID-19 by targeting endoribonuclease NSP15

Dhanabalan¹,

Sangeetha²,

Vajravijayan³

et al. 2020

Informatics in Medicine Unlocked

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The world is facing health and economic havoc due to the Corona Virus Disease-2019 (COVID-19) pandemic. Given the number of affected people and the mortality rate, the virus is undoubtedly a serious threat to humanity. By analogy with earlier reports about Severe Acute Respiratory Syndrome (SARS-CoV) and Middle East Respiratory Syndrome (MERS-CoV) - viruses, the novel Coronavirus’ replication mechanism is likely well understood. The structure of an endoribonuclease (NSP15) of SARS-CoV-2 was reported recently. This enzyme is expected to play a crucial role in replication. In this work, attempts were made to identify inhibitors of this enzyme. To achieve the goal, high throughput in silico screening and molecular docking procedures were performed. From an Enamine database of a billion compounds, 3978 compounds with potential antiviral activity were selected for screening and induced fit docking that funneled down to eight compounds with good docking score and docking energy. Detailed analysis of non-covalent interactions at the active site and the apparent match of the molecule with the shape of the binding pocket were assessed. All the compounds show significant interactions for tight binding. Since all the compounds are synthetic with favorable drug-like properties, these may be considered for immediate optimization and downstream applications.

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Potential inhibitors of the interaction between ACE2 and SARS-CoV-2 (RBD), to develop a drug

Cited by 46 publications

References 41 publications

Quinolines-Based SARS-CoV-2 3CLpro and RdRp Inhibitors and Spike-RBD-ACE2 Inhibitor for Drug-Repurposing Against COVID-19: An in silico Analysis

Quinolines-Based SARS-CoV-2 3CLpro and RdRp Inhibitors and Spike-RBD-ACE2 Inhibitor for Drug-Repurposing Against COVID-19: An in silico Analysis

ACE2: from protection of liver disease to propagation of COVID-19

Structure-based drug designing towards the identification of potential anti-viral for COVID-19 by targeting endoribonuclease NSP15

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