Evaluation of Flavonoids as 2019-nCoV Cell Entry Inhibitor Through Molecular Docking and Pharmacological Analysis

Bhowmik, Deep; Nandi, Rajat; Kumar, Diwakar

doi:10.26434/chemrxiv.12071508

Cited by 15 publications

(14 citation statements)

References 51 publications

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“…In the literature, there were no reports of the interaction of peonidine and pelargonidine with target proteins. On the other hand, only one study was found regarding the interaction of naringin with the RBD of the spike protein of 2019-nCoV (Bhowmik et al., 2020 ). According to the results of this study conducted using PyRx and iGEMDOCK, it was determined that the binding affinity of naringin to spike protein was −8.3 kcal/mol.…”

Section: Resultsmentioning

confidence: 99%

In silico analysis of the interactions of certain flavonoids with the receptor-binding domain of 2019 novel coronavirus and cellular proteases and their pharmacokinetic properties

İstifli

Netz

Tepe

et al. 2020

Journal of Biomolecular Structure and Dynamics

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Coronavirus Disease 2019 (COVID-19) has infected more than thirty five million people worldwide and caused nearly 1 million deaths as of October 2020. The microorganism causing COVID-19 was named as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2 or 2019-nCoV). The aim of this study was to investigate the interactions of twenty-three phytochemicals belonging to different flavonoid subgroups with the receptor binding domain (RBD) of the spike glycoprotein of 2019-nCoV, and cellular proteases [transmembrane serine protease 2 (TMPRSS2), cathepsin B and L (CatB/L)]. The compounds interacted more strongly with CatB and CatL than with the other proteins. Van der Waals and hydrogen bonds played an important role in the receptor-ligand interactions. As a result of RBCI (relative binding capacity index) analysis conducted to rank flavonoids in terms of their interactions with the target proteins, (-) -epicatechin gallate interacted strongly with all the proteins studied. The results obtained from molecular dynamics and molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) methods also supported this data. According to Lipinski's rule of five, (-) -epicatechin gallate showed drug-likeness properties. Although this molecule is not capable of crossing the blood-brain barrier (BBB), it was concluded that (-) -epicatechin gallate can be evaluated as a candidate molecule in drug development studies against 2019-nCoV since it was not the substrate of P-gp (P-glycoprotein), did not inhibit any of the cytochrome Ps, and did not show AMES toxicity or hepatotoxicity on eukaryotic cells.

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Section: Resultsmentioning

confidence: 99%

In silico analysis of the interactions of certain flavonoids with the receptor-binding domain of 2019 novel coronavirus and cellular proteases and their pharmacokinetic properties

İstifli

Netz

Tepe

et al. 2020

Journal of Biomolecular Structure and Dynamics

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“…The high reactivity of the resorcinol structure is primarily associated with the location of these two hydroxyl groups in the benzene ring [ 110 ]. The resorcinol moiety of ring A might play a role in ACE2 inhibition, as this group might disrupt hydrogen bonds between Glu329/Gln325 of ACE2 and Arg426 of the S protein of SARS CoV-2, which form a salt bridge to stabilize their interaction [ 72 , 73 ].This hydrophobic interaction occurs in ring C with some non-polar amino acid residues such as Gly354, Asp355, and Phe356 [ 111 ].…”

Section: Flavonoids As Ace2 Inhibitorsmentioning

confidence: 99%

Natural Flavonoids as Potential Angiotensin-Converting Enzyme 2 Inhibitors for Anti-SARS-CoV-2

et al. 2020

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Over the years, coronaviruses (CoV) have posed a severe public health threat, causing an increase in mortality and morbidity rates throughout the world. The recent outbreak of a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the current Coronavirus Disease 2019 (COVID-19) pandemic that affected more than 215 countries with over 23 million cases and 800,000 deaths as of today. The situation is critical, especially with the absence of specific medicines or vaccines; hence, efforts toward the development of anti-COVID-19 medicines are being intensively undertaken. One of the potential therapeutic targets of anti-COVID-19 drugs is the angiotensin-converting enzyme 2 (ACE2). ACE2 was identified as a key functional receptor for CoV associated with COVID-19. ACE2, which is located on the surface of the host cells, binds effectively to the spike protein of CoV, thus enabling the virus to infect the epithelial cells of the host. Previous studies showed that certain flavonoids exhibit angiotensin-converting enzyme inhibition activity, which plays a crucial role in the regulation of arterial blood pressure. Thus, it is being postulated that these flavonoids might also interact with ACE2. This postulation might be of interest because these compounds also show antiviral activity in vitro. This article summarizes the natural flavonoids with potential efficacy against COVID-19 through ACE2 receptor inhibition.

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“…Crystal structure modeling of both ACE-2 and SARS-CoV-2 S protein has identified flavonoids, a subgroup of phenolic compounds, as suitable candidates for binding and inhibiting both molecules in silico [ 60 ]. Assessment has started on these compounds in vitro, and there are successes showing SARS-CoV-2 inhibition with phenolic compounds also effective against SARS-CoV [ 61 , 62 ].…”

Section: Interventionsmentioning

confidence: 99%

Influence of Herbal Medicines on HMGB1 Release, SARS-CoV-2 Viral Attachment, Acute Respiratory Failure, and Sepsis. A Literature Review

Wyganowska‐Świątkowska¹,

Nohawica²,

Grocholewicz

et al. 2020

IJMS

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By attaching to the angiotensin converting enzyme 2 (ACE2) protein on lung and intestinal cells, Sudden Acute Respiratory Syndrome (SARS-CoV-2) can cause respiratory and homeostatic difficulties leading to sepsis. The progression from acute respiratory failure to sepsis has been correlated with the release of high-mobility group box 1 protein (HMGB1). Lack of effective conventional treatment of this septic state has spiked an interest in alternative medicine. This review of herbal extracts has identified multiple candidates which can target the release of HMGB1 and potentially reduce mortality by preventing progression from respiratory distress to sepsis. Some of the identified mixtures have also been shown to interfere with viral attachment. Due to the wide variability in chemical superstructure of the components of assorted herbal extracts, common motifs have been identified. Looking at the most active compounds in each extract it becomes evident that as a group, phenolic compounds have a broad enzyme inhibiting function. They have been shown to act against the priming of SARS-CoV-2 attachment proteins by host and viral enzymes, and the release of HMGB1 by host immune cells. An argument for the value in a nonspecific inhibitory action has been drawn. Hopefully these findings can drive future drug development and clinical procedures.

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Evaluation of Flavonoids as 2019-nCoV Cell Entry Inhibitor Through Molecular Docking and Pharmacological Analysis

Cited by 15 publications

References 51 publications

In silico analysis of the interactions of certain flavonoids with the receptor-binding domain of 2019 novel coronavirus and cellular proteases and their pharmacokinetic properties

In silico analysis of the interactions of certain flavonoids with the receptor-binding domain of 2019 novel coronavirus and cellular proteases and their pharmacokinetic properties

Natural Flavonoids as Potential Angiotensin-Converting Enzyme 2 Inhibitors for Anti-SARS-CoV-2

Influence of Herbal Medicines on HMGB1 Release, SARS-CoV-2 Viral Attachment, Acute Respiratory Failure, and Sepsis. A Literature Review

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