Flavonols as potential antiviral drugs targeting SARS-CoV-2 proteases (3CLpro and PLpro), spike protein, RNA-dependent RNA polymerase (RdRp) and angiotensin-converting enzyme II receptor (ACE2)

Mouffouk, Chaima; Mouffouk, Soumia; Mouffouk, Sara; Hambaba, Leila; Haba, Hamada

doi:10.1016/j.ejphar.2020.173759

Cited by 122 publications

(109 citation statements)

References 132 publications

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“…After the fusion of SARS-CoV-2 with the host cell, the viral RNA is released into the cytosol, which is translated into the replicase proteins [15]. 3CL pro and PL pro cleave the replicase polyprotein into 15-16 nonstructural proteins (nsps) at consensus cleavage sites [28,[39][40][41]. Some of these nsps encode proteins with essential functions for virus-mediated RNA replication, so targeting these proteins is an effective antiviral strategy for suppressing viral genome replication in order to cure CoV infection.…”

Section: C-like Protease and Papain-like Proteasementioning

confidence: 99%

Therapeutic Potential of Glycosyl Flavonoids as Anti-Coronaviral Agents

2021

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The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread all over the world, creating a devastating socio-economic impact. Even though protective vaccines are starting to be administered, an effective antiviral agent for the prevention and treatment of COVID-19 is not available yet. Moreover, since new and deadly CoVs can emerge at any time with the potential of becoming pandemics, the development of therapeutic agents against potentially deadly CoVs is a research area of much current interest. In the search for anti-coronaviral drugs, researchers soon turned their heads towards glycosylated flavonoids. Glycosyl flavonoids, widespread in the plant kingdom, have received a lot of attention due to their widely recognized antioxidant, anti-inflammatory, neuroprotective, anticarcinogenic, antidiabetic, antimicrobial, and antiviral properties together with their capacity to modulate key cellular functions. The wide range of biological activities displayed by glycosyl flavonoids, along with their low toxicity, make them ideal candidates for drug development. In this review, we examine and discuss the up-to-date developments on glycosyl flavonoids as evidence-based natural sources of antivirals against coronaviruses and their potential role in the management of COVID-19.

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Section: C-like Protease and Papain-like Proteasementioning

confidence: 99%

Therapeutic Potential of Glycosyl Flavonoids as Anti-Coronaviral Agents

2021

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“… Quercetin Inhibits viral entry and translation Ebola virus [ 12 ] Polio virus [ 13 ] Hepatitis C [ 14 ] Coronavirus [ 15 ] Mango virus [ 16 ] Pseudorabies virus [ 17 ] 2 Resveratrol Inhibits replication, protein synthesis, gene expression, and nucleic acid synthesis of virus Inhibits viral attachment. HSV [ 18 ] Influenza [ 19 ] Rhinovirus [ 20 ] MERS-CoV [ 21 ] 3 Fisetin, rutin Induce inhibition of cytokine expression and synthesis H1N1 [ 22 ] 4 Catechin Epicatechin Epicatechingallate Inhibits viral binding. Sindabis virus [ 23 ] 5 Morin, galangin Inhibits NLRP3 inflammasome Poliovirus 1 HSV-1 & 2 RSV HCV CDV SARS-CoV [ 22 ] 6 Kaempferol Inhibits secretion of many cytokines including IL-6 and IL-8.…”

Section: Synergistic Approach (Brain Boosting and Anti-viral Target Cmentioning

confidence: 99%

“… HSV [ 18 ] Influenza [ 19 ] Rhinovirus [ 20 ] MERS-CoV [ 21 ] 3 Fisetin, rutin Induce inhibition of cytokine expression and synthesis H1N1 [ 22 ] 4 Catechin Epicatechin Epicatechingallate Inhibits viral binding. Sindabis virus [ 23 ] 5 Morin, galangin Inhibits NLRP3 inflammasome Poliovirus 1 HSV-1 & 2 RSV HCV CDV SARS-CoV [ 22 ] 6 Kaempferol Inhibits secretion of many cytokines including IL-6 and IL-8. Human cytomegalovirus Coxsackie B virus [ 24 , 25 ] 7 Myricetin Inhibits ATPase activity SARS-CoV [ 26 ] 8 Theaflavin Inhibits RdRp activity SARS-CoV-2 [ 26 ] 9 Caffeine Promising inhibitors for 3-chymotrypsin-like protease of SARS-CoV-2 SARS-CoV-2 [ 27 ] 10 Tingenone Inhibits SARS-CoV 3CLpro SARS-CoV [ 26 ] 11 Quercetin-3-β-galactoside Competitively inhibits SARS-CoV 3CLpro SARS-CoV [ 26 ] 12 Emodin Blocks the binding of S protein to ACE2 SARS-CoV [ 26 ] HSV-herpes simplex virus, MERS-CoV-Middle East respiratory syndrome coronavirus, H1N1-influenza A virus, RSV-respiratory syncytial virus, CA-Coxsackievirus, CDV-canine distemper virus, SARS–CoV severe acute respiratory syndrome coronavirus.…”

Section: Synergistic Approach (Brain Boosting and Anti-viral Target Cmentioning

confidence: 99%

Exploitation of polyphenols and proteins using nanoencapsulation for anti-viral and brain boosting properties – Evoking a synergistic strategy to combat COVID-19 pandemic

Noor

Gani

et al. 2021

International Journal of Biological Macromolecules

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The world is currently under the threat of COVID pandemic and has focused every dimension of research in finding a cure to this novel disease. In this current situation, people are facing mental stress, agony, fear, depression and other associated symptoms which are taking a toll on their overall mental health. Nanoencapsulation of certain brain boosting polyphenols including quercetin, caffeine, cocoa flavanols and proteins like lectins can become new area of interest in the present scenario. Besides the brain boosting benefits, we have also highlighted the anti- viral activities of these compounds which we assume can play a possible role in combating COVID-19 given to their previous history of action against certain viruses. This review outlines the nanoencapsulation approaches of such synergistic compounds as a novel strategy to take the ongoing research a step ahead and also provides a new insight in bringing the role of nanotechnology in addressing the issues related to COVID pandemic.

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“…In their study, they disclosed 8 novel druggable binding sites of spike protein ( Ugur Marion & Marion, 2020 ). In one of the studies, the scientists tested the potential of flavonols to act as antiviral drugs by targeting spike protein, SARS-CoV-2 proteases, RNA-dependent RNA polymerase, and ACE2 receptor ( Mouffouk et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

A molecular dynamics simulation study of the ACE2 receptor with screened natural inhibitors to identify novel drug candidate against COVID-19

Srivastava

Garg

Srivastava

et al. 2021

PeerJ

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Background & Objectives The massive outbreak of Novel Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) has turned out to be a serious global health issue worldwide. Currently, no drugs or vaccines are available for the treatment of COVID-19. The current computational study was attempted to identify a novel therapeutic inhibitor against novel SARS-CoV-2 using in silico drug discovery pipeline. Methods In the present study, the human angiotensin-converting enzyme 2 (ACE2) receptor was the target for the designing of drugs against the deadly virus. The 3D structure of the receptor was modeled & validated using a Swiss-model, Procheck & Errat server. A molecular docking study was performed between a group of natural & synthetic compounds having proven anti-viral activity with ACE2 receptor using Autodock tool 1.5.6. The molecular dynamics simulation study was performed using Desmond v 12 to evaluate the stability and interaction of the ACE2 receptor with a ligand. Results Based on the lowest binding energy, confirmation, and H-bond interaction, cinnamic acid (−5.20 kcal/mol), thymoquinone (−4.71 kcal/mol), and andrographolide (Kalmegh) (−4.00 kcal/mol) were screened out showing strong binding affinity to the active site of ACE2 receptor. MD simulations suggest that cinnamic acid, thymoquinone, and andrographolide (Kalmegh) could efficiently activate the biological pathway without changing the conformation in the binding site of the ACE2 receptor. The bioactivity and drug-likeness properties of compounds show their better pharmacological property and safer to use. Interpretation & Conclusions The study concludes the high potential of cinnamic acid, thymoquinone, and andrographolide against the SARS-CoV-2 ACE2 receptor protein. Thus, the molecular docking and MD simulation study will aid in understanding the molecular interaction between ligand and receptor binding site, thereby leading to novel therapeutic intervention.

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Flavonols as potential antiviral drugs targeting SARS-CoV-2 proteases (3CLpro and PLpro), spike protein, RNA-dependent RNA polymerase (RdRp) and angiotensin-converting enzyme II receptor (ACE2)

Cited by 122 publications

References 132 publications

Therapeutic Potential of Glycosyl Flavonoids as Anti-Coronaviral Agents

Therapeutic Potential of Glycosyl Flavonoids as Anti-Coronaviral Agents

Exploitation of polyphenols and proteins using nanoencapsulation for anti-viral and brain boosting properties – Evoking a synergistic strategy to combat COVID-19 pandemic

A molecular dynamics simulation study of the ACE2 receptor with screened natural inhibitors to identify novel drug candidate against COVID-19

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