Comparative docking of SARS-CoV-2 receptors antagonists from repurposing drugs

Oliveira, Lima de; Km, Teixeira de Oliveira

doi:10.26434/chemrxiv.12044538.v4

Cited by 4 publications

(3 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Oliveira and colleagues [65] performed molecular docking with the ACE2 receptor in complex with S-glycoprotein SARS-CoV-2 (PDB ID: 6M0J) using 60 drugs, which were published in the literature against SARS-CoV-2. The docking result showed that paritaprevir and ivermectin have highest binding affinity to the ACE2 receptor with interaction energies of −11.8 kcal mol −1 and −11.6 kcal mol −1 , respectively (Fig.…”

Section: Repurposed Ace2 Inhibitorsmentioning

confidence: 99%

The Repurposed ACE2 Inhibitors: SARS-CoV-2 Entry Blockers of Covid-19

et al. 2021

View full text Add to dashboard Cite

The highly infectious disease COVID-19 is induced by SARS-coronavirus 2 (SARS-CoV-2), which has spread rapidly around the globe and was announced as a pandemic by the World Health Organization (WHO) in March 2020. SARS-CoV-2 binds to the host cell's angiotensin converting enzyme 2 (ACE2) receptor through the viral surface spike glycoprotein (S-protein). ACE2 is expressed in the oral mucosa and can therefore constitute an essential route for entry of SARS-CoV-2 into hosts through the tongue and lung epithelial cells. At present, no effective treatments for SARS-CoV-2 are yet in place. Blocking entry of the virus by inhibiting ACE2 is more advantageous than inhibiting the subsequent stages of the SARS-CoV-2 life cycle. Based on current published evidence, we have summarized the different in silico based studies and repurposing of anti-viral drugs to target ACE2, SARS-CoV-2 S-Protein: ACE2 and SARS-CoV-2 S-RBD: ACE2. This review will be useful to researchers looking to effectively recognize and deal with SARS-CoV-2, and in the development of repurposed ACE2 inhibitors against COVID-19.) • COVID-19 Abbreviations CoV Coronavirus + ssRNA Single-stranded RNA ICTV International Committee on Taxonomy of Viruses SARS severe acute respiratory syndrome SARS-CoV 1 Severe acute respiratory syndrome coronavirus 1 This article is part of the Topical Collection ''Antiviral Drug Research''; edited by Guangxin Liang, Zheng Yin.

show abstract

Section: Repurposed Ace2 Inhibitorsmentioning

confidence: 99%

The Repurposed ACE2 Inhibitors: SARS-CoV-2 Entry Blockers of Covid-19

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The World Health Organization (WHO) declared the COVID-19 outbreak as a new pandemic on 11 March 2020 [2]. In order to contribute to the front line of the fight against this disease, researchers worldwide are moving to an investigation of an effective treatment regimen (based mainly on known drugs) against infection caused by the SARS-CoV-2 virus [1][2][3][4][5]. Most recently, the combination of drugs, for example, (hydroxy)chloroquine with azithromycin (AZ), has been used as a strategy and has also been clinically tested to treat the SARS-CoV-2 outbreak [6][7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

New In Silico Insights into the Application of (Hydroxy)Chloroquine with Macrolide Antibiotic Co-Crystals against the SARS-CoV-2 Virus

Castro

Assis

Cunha

et al. 2022

COVID

View full text Add to dashboard Cite

In this in silico study, different pharmaceutical co-crystals based on (hydroxy)chloroquine with macrolide antibiotics (azithromycin, clarithromycin, or erythromycin A) were analyzed for the first time. These findings present a new molecular perspective and therefore suggest that the combination of (hydroxy)chloroquine/azithromycin, in the stoichiometric ratio of 1:1, as model co-crystal systems has less toxicity and is the most effective for inhibiting the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

show abstract

“…To stop the cytokine storm of severe COVID-19, IL-6R blockers have been proposed as effective drugs. The drug tocilizumab has been suggested as an effective antagonist to block IL-6 signal transduction pathway [16,17]. Possible effectiveness of Tocilizumab treatment has been revealed by single-cell analysis against severe COVID-19 infection [18] and researchers hypothesized preventing COVID-19 induced pneumonia with possible cytokine blockers [19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Mitigate the cytokine storm due to the severe COVID-19: A computational investigation of possible allosteric inhibitory actions on IL-6R and IL-1R using selected phytochemicals

et al. 2020

View full text Add to dashboard Cite

The novel corona virus 2019 (COVID 19) is growing at an increasing rate with high mortality. Meanwhile, the cytokine storm is the most dangerous and potentially life-threatening event related to COVID 19. Phyto-compounds found in existing Ayurveda drugs have the ability to inhibit the Interleukin 6 (IL-6R) and Interleukin 1 (IL-1R) receptors. IL-6R and IL-1R receptors involve in cytokine storm and recognition of phytochemicals with proven safety profiles could open a pathway to the development of the most effective drugs against cytokine storm. In this study, we intend to perform an in silico investigation of effective phyto compounds, which can be isolated from selected medicinal herbs to avoid cytokine storm, inhibiting the IL-6 and IL-1 receptor binding process. An extensive literature survey followed by virtual screening was carried out to identify phytochemicals with potential anti-hyper-inflammatory action. Flexible docking was conducted for validated models of IL-1R and IL-6R-α with the most promising phytochemicals at possible allosteric sites using AutoDock Vina. Molecular dynamics (MD) studies were conducted for selected protein-ligand complexes using LARMD server and conformational changes were evaluated. According to the results, taepeenin J had Gibbs energy (ΔG) of -10.85 kcal/mol towards IL-1R but had limited oral bioavailability. MD analysis revealed that taepeenin J can cause significant conformational movements in IL-1R. Nortaepeenin B showed a ΔG of -8.5 kcal/mol towards IL-6R-α with an excellent oral bioavailability. MD analysis predicted that it can cause significant conformational movements in IL-6R-α. Hence, the evaluated phytochemicals are potential candidates for further in vitro studies for the development of medicine against cytokine storm on behalf of SARS-COV-2 infected patients.

show abstract

Comparative docking of SARS-CoV-2 receptors antagonists from repurposing drugs

Cited by 4 publications

References 43 publications

The Repurposed ACE2 Inhibitors: SARS-CoV-2 Entry Blockers of Covid-19

The Repurposed ACE2 Inhibitors: SARS-CoV-2 Entry Blockers of Covid-19

New In Silico Insights into the Application of (Hydroxy)Chloroquine with Macrolide Antibiotic Co-Crystals against the SARS-CoV-2 Virus

Mitigate the cytokine storm due to the severe COVID-19: A computational investigation of possible allosteric inhibitory actions on IL-6R and IL-1R using selected phytochemicals

Contact Info

Product

Resources

About