scholarly journals SARS-COV-2 Spike Glycoprotein as Inhibitory Target for In silico Screening of Natural Compounds

2021 ◽  
Vol 11 (6) ◽  
pp. 14974-14985
Keyword(s):  
In Silico ◽  
Md Simulation ◽  
Simulation Analysis ◽  
Binding Pocket ◽  
Natural Compounds ◽  
Spike Glycoprotein ◽  
Life Threatening ◽  
Inhibitory Potential ◽  
The Stability ◽  
Approved Drugs

Coronavirus disease (Covid-19) caused by SARS-Cov-2 has raised global health concerns without approved drugs to manage this life-threatening disease. This study aimed to predict the inhibitory potential of quercetin-3-o-rutinoside against SARS-Cov-2 spike glycoprotein. Targeting the SARS-Cov-2 Nucleocapsid spike glycoprotein (pdb id: 6m3m) is gaining importance. In this present study, the relationship between plant-derived natural drug and spike glycoprotein was predicted using in silico computational approach. The results were evaluated according to the glide (Schrodinger) dock score. Among the five (5) screened natural compounds, quercetin-3-o-rutinoside has the best docking score (-9.296) with the target. Molecular dynamic (MD) simulation analysis was performed for 1000ps to confirm the spike protein's stability behavior and quercetin-3-o-rutinoside complex. The MD simulation analysis validated the stability of quercetin-3-o-rutinoside in the spike protein binding pocket as a potent inhibitor. The pharmacokinetics screening of the natural compounds showed that quercetin-3-o-rutinoside possesses good oral bioavailability with no side effects.

scholarly journals SARS-COV-2 Spike Glycoprotein as Inhibitory Target for Insilico Screening of Natural Compounds

2021 ◽  
Author(s):  
Damilola Alex Omoboyowa ◽  
Balogun Toheeb A ◽  
Onyeka S. Chukwudozie ◽  
Victor N. Nweze ◽  
Oluwatosin A. Saibu ◽  
...  
Keyword(s):  
Simulation Study ◽  
Md Simulation ◽  
Binding Pocket ◽  
Spike Protein ◽  
Health Concern ◽  
Spike Glycoprotein ◽  
Angiotensin Converting Enzyme 2 ◽  
Computational Relationship ◽  
Inhibitory Potential ◽  
The Stability

Abstract Coronavirius disease 2019 (Covid-19) pandemic caused by SARS-Cov-2 has raised global health concern without approved drug for management of this lie threatening disease. The aim of this study was to predict the inhibitory potential of quercetin-3-o-rutinoside against SARS-Cov-2 spike glycoprotein. Targeting the SARS-Cov-2 spike protein from angiotensin converting enzyme 2 complex (pdb: 6lzg) is gaining importance. In this study, in silico computational relationship between plant-derived natural drug and spike glycoprotein was predicted. The results were evaluated based on glide (Schrodinger) dock score. Among the five (5) screened compounds, quercetin-3-o-rutinoside has the best docking score (-9.296) with the target. Molecular dynamic (MD) simulation study was performed for 1000ps to confirm the stability behavior of the spike protein and quercetin-3-o-rutinoside complex. The MD simulation study validated the stability of quercetin-3-o-rutinoside in the spike protein binding pocket as potent inhibitor.

In silico identification of new anti-SARS-CoV-2 agents from bioactive phytocompounds targeting the viral spike glycoprotein and human TLR4

2021 ◽  
Vol 18 ◽  
Author(s):  
Nabarun Chandra Das ◽  
Rajendra Kumar Labala ◽  
Ritwik Patra ◽  
Asamanja Chattoraj ◽  
Suprabhat Mukherjee
Keyword(s):  
In Silico ◽  
Md Simulation ◽  
Docking Study ◽  
Spike Glycoprotein ◽  
Molecular Docking Study ◽  
S Protein ◽  
Proinflammatory Responses ◽  
Experimental Validations ◽  
The Stability ◽  
Novel Coronavirus

Background: The recent outbreak of novel coronavirus disease (COVID-19) pandemic caused by SARS-CoV-2 has posed a tremendous threat to mankind. The unavailability of a specific drug or vaccine has been the major concern to date. Spike (S) glycoprotein of SARS-CoV-2 plays the most crucial role in the viral infection and immunopathogenesis, and hence this protein appears to be an efficacious target for drug discovery. Objective: Identifying potent bioactive phytocompound that can target viral spike (S) glycoprotein and human TLR4 to reduce immunopathological manifestations of COVID-19. Method: A series of thirty (30) bioactive phytocompounds, previously documented for antiviral activity, were theoretically screened for their binding efficacy against key proteins related to pathogenesis of SARSCoV-2 namely viral spike (S) glycoprotein and human TLR4. MD simulation was employed to verify the postulations of molecular docking study and further ADME analysis was performed to predict the most effective one. Results: Studies hypothesized that two new phytochemicals viz. cajaninstilbene acid (-8.83 kcal/mol) and papaverine (-5.81 kcal/mol) might be the potent inhibitors of spike glycoprotein with stout binding affinity and favourable ADME attributes. MD simulation further ratified the stability of the docked complexes between the phytochemicals and S protein through strong hydrogen bonding. Our in silico data also indicated that cajaninstilbene acid and papaverine might block human TLR4 which could be useful to mitigate SARS-CoV-2-induced lethal proinflammatory responses. Conclusion: Experimental data collectively predict cajaninstilbene acid as the potential blocker of S protein which may be used as anti-viral against COVID-19 in the future. However, further experimental validations alongside toxicological detailing are needed for claiming the candidature of these molecules as future anti-corona therapeutics.

Virtual screening of potential therapeutic inhibitors against spike, helicase and polymerase of SARS-CoV-2 (COVID-19)

Coronaviruses ◽  
2020 ◽  
Vol 01 ◽  
Author(s):  
Ayesha Tazeen ◽  
Farah Deeba ◽  
Aftab Alam ◽  
Rafat Ali ◽  
Romana Ishrat ◽  
...  
Keyword(s):  
Catalytic Domain ◽  
Nigella Sativa ◽  
Therapeutic Option ◽  
Natural Compounds ◽  
Host Cells ◽  
Nucleoside Triphosphate ◽  
Symptomatic Management ◽  
Replication Inhibitor ◽  
Inhibitory Potential ◽  
Approved Drugs

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected around 13 million people and has caused more than 5.7 lakh deaths worldwide since December 2019. In the absence of FDA approved drug for its treatment, only symptomatic management is done. Methods: We attempted to uncover potential therapeutic targets of spike, helicase and RNA dependent RNA polymerase (RdRp) proteins of the SARS-CoV-2 employing computational approach. The PDB structure of spike and RdRp and predicted structure of helicase proteins were docked with 100 approved antiviral drugs, natural compounds and some other chemical compounds. Results: The anti-SARS ligands EK1 and CID_23631927, and NCGC00029283 are potential entry inhibitor as it showed affinity with immunogenic receptor binding domain (RBD) of spike protein. This RBD interacts with angiotensin converting enzyme (ACE2) receptor facilitating the entry of virion in the host cells. The FDA approved drugs including Nelfinavir, Saquinavir, Tipranavir, Setrobuvir, Indinavir and Atazanavir showed potential inhibitory activity against targeted domains and thus may act as entry or replication inhibitor or both. Furthermore, several anti-HCoV natural compounds including Amentoflavone, Rutin and Tannin are also potential entry and replication inhibitor as they showed affinity with RBD, Ploop containing nucleoside triphosphate hydrolase and catalytic domain of the respective protein. Dithymoquinone showed significant inhibitory potential against the fusion peptide of S2 domain. Importantly, Tannin, Dithymoquinone and Rutin can be extracted from Nigella sativa seeds and thus may prove to be one of the most potential anti-SARS-CoV-2 inhibitor. Conclusion: Several potential ligands were identified with already known anti-HCoVs activities. Furthermore, as our study showed that some of the ligands acted as both entry or replication inhibitor against SARS-CoV-2, it is envisaged that a combination of either inhibitors with a dual mode of action would prove to be a much desired therapeutic option against this viral infection.

scholarly journals Modulating the voltage sensor of a cardiac potassium channel shows antiarrhythmic effects

2021 ◽  
Author(s):  
Yangyang Lin ◽  
Sam Z. Grinter ◽  
Zhongju Lu ◽  
Xianjin Xu ◽  
Hong Zhan Wang ◽  
...  
Keyword(s):  
Action Potential ◽  
In Silico ◽  
Therapeutic Efficacy ◽  
Torsade De Pointes ◽  
Computational Prediction ◽  
Chemical Library ◽  
Drug Induced ◽  
Voltage Dependent ◽  
Life Threatening ◽  
Approved Drugs

AbstractCardiac arrhythmias are the most common cause of sudden cardiac death worldwide. Lengthening the ventricular action potential duration (APD) either congenitally or via pathologic or pharmacologic means, predisposes to a life-threatening ventricular arrhythmia, Torsade de Pointes. IKs, a slowly activating K+ current plays a role in action potential repolarization. In this study, we screened a chemical library in silico by docking compounds to the voltage sensing domain (VSD) of the IKs channel. Here we show that C28 specifically shifted IKs VSD activation in ventricle to more negative voltages and reversed drug-induced lengthening of APD. At the same dosage, C28 did not cause significant changes of the normal APD in either ventricle or atrium. This study provides evidence in support of a computational prediction of IKs VSD activation as a potential therapeutic approach for all forms of APD prolongation. This outcome could expand the therapeutic efficacy of a myriad of currently approved drugs that may trigger arrhythmias.Significance statementC28, identified by in silico screening, specifically facilitated voltage dependent activation of a cardiac potassium ion channel, IKs. C28 reversed drug-induced prolongation of action potentials, but minimally affected the normal action potential at the same dosage. This outcome supports a computational prediction of modulating IKs activation as a potential therapy for all forms of action potential prolongation, and could expand therapeutic efficacy of many currently approved drugs that may trigger arrhythmias.

scholarly journals Study of Caspase 8 Inhibition for the Management of Alzheimer’s Disease: A Molecular Docking and Dynamics Simulation

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2071
Author(s):  
Syed Sayeed Ahmad ◽  
Meetali Sinha ◽  
Khurshid Ahmad ◽  
Mohammad Khalid ◽  
Inho Choi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Docking ◽  
Md Simulation ◽  
Simulation Analysis ◽  
Dynamics Simulation ◽  
Caspase 8 ◽  
Amino Acid Residues ◽  
The Stability ◽  
Molecular Docking And Dynamics

Alzheimer’s disease (AD) is the most common type of dementia and usually manifests as diminished episodic memory and cognitive functions. Caspases are crucial mediators of neuronal death in a number of neurodegenerative diseases, and caspase 8 is considered a major therapeutic target in the context of AD. In the present study, we performed a virtual screening of 200 natural compounds by molecular docking with respect to their abilities to bind with caspase 8. Among them, rutaecarpine was found to have the highest (negative) binding energy (−6.5 kcal/mol) and was further subjected to molecular dynamics (MD) simulation analysis. Caspase 8 was determined to interact with rutaecarpine through five amino acid residues, specifically Thr337, Lys353, Val354, Phe355, and Phe356, and two hydrogen bonds (ligand: H35-A: LYS353:O and A:PHE355: N-ligand: N5). Furthermore, a 50 ns MD simulation was conducted to optimize the interaction, to predict complex flexibility, and to investigate the stability of the caspase 8–rutaecarpine complex, which appeared to be quite stable. The obtained results propose that rutaecarpine could be a lead compound that bears remarkable anti-Alzheimer’s potential against caspase 8.

scholarly journals Gymnema Sylvestre A- Potential Inhibitor of COVID-19 Main Protease by MD Simulation Study

2020 ◽  
Author(s):  
Senthil Kumar Subramani ◽  
Yash Gupta ◽  
Manish Manish ◽  
GBKS Prasad
Keyword(s):  
Md Simulation ◽  
Docking Study ◽  
Binding Pocket ◽  
Gymnema Sylvestre ◽  
Molecular Docking Study ◽  
Main Protease ◽  
Strong Candidate ◽  
The Stability ◽  
Potential Inhibitors ◽  
Domain I

Gymnema sylvestre (GS) is one of the herbal plant used since in ancient times. The present study aimed to assess bioactive compounds GS mainly gymnemic acids as potential inhibitors for COVID-19 against Mpro enzyme using a molecular docking study. The docking score observed between -53.4 to - 42.4 of all gymnemic acids and its derivatives. Molecular Dynamics (MD) simulation studies carried out at 100ns supported the stability of GS molecules within the binding pocket. RMSD score of less than 3.6. mainly, our results supported that these GS molecules bind to the domain I & II, and domain II-III linker of 3CLpro enzyme, suggesting its suitability as strong candidate for therapeutic against COVID-19. <br>

scholarly journals Repurposing the Natural Compound for Antiviral During an Epidemic -a Case Study on the Drug Repurpose of Natural Compounds to Treat COVID-19

2020 ◽  
Author(s):  
Zhihao Wang ◽  
Chi Xu ◽  
Bing Liu ◽  
Nan Qiao
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Natural Compound ◽  
Early Stage ◽  
Drug Repurposing ◽  
The United States ◽  
Natural Compounds ◽  
Global Scale ◽  
Novel Coronavirus ◽  
Approved Drugs

<p>The pandemic caused by the novel coronavirus SARS-CoV-2 is rapidly spreading and infecting the population on the global scale, it is a global health threat due to its high infection rate, high mortality and the lack of clinically approved drugs and vaccines for treating the disease (COVID-19). Utilising the published structures and homologue remodelling for proteins from SARS-CoV-2, an <i>in silico</i> molecular docking based screening was conducted and deposited in the Shennong project database. The results from the screening could be used to explain the clinical observation of repurposing the Ritonavir and Lopinavir to treat patients in the early stage of COVID-19 infection, and the prescription of Remdisivir in the United States as the therapy. Additionally, this molecular docking identified natural compound candidates for drug repurposing. This <i>in silico </i>molecular docking screen may be used for the initatial evaluation and rationalisation for drug repurposing of other potential candidates, especially other natural compounds from traditional Chinese medicines.</p>

scholarly journals Pharmacoinformatics-based investigation of bioactive compounds of Rasam (South Indian recipe) against human cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Arjun Kumar Kalimuthu ◽  
Theivendren Panneerselvam ◽  
Parasuraman Pavadai ◽  
Sureshbabu Ram Kumar Pandian ◽  
Krishnan Sundar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bioactive Compounds ◽  
In Silico ◽  
Md Simulation ◽  
Human Cancer ◽  
Binding Energies ◽  
Mitogen Activated Protein Kinase ◽  
Molecular Docking Study ◽  
South Indian ◽  
The Stability

AbstractSpice-rich recipes are referred to as “functional foods” because they include a variety of bioactive chemicals that have health-promoting properties, in addition to their nutritional value. Using pharmacoinformatics-based analysis, we explored the relevance of bioactive chemicals found in Rasam (a South Indian cuisine) against oxidative stress-induced human malignancies. The Rasam is composed of twelve main ingredients, each of which contains a variety of bioactive chemicals. Sixty-six bioactive compounds were found from these ingredients, and their structures were downloaded from Pubchem. To find the right target via graph theoretical analysis (mitogen-activated protein kinase 6 (MAPK6)) and decipher their signaling route, a network was built. Sixty-six bioactive compounds were used for in silico molecular docking study against MAPK6 and compared with known MAPK6 inhibitor drug (PD-173955). The top four compounds were chosen for further study based on their docking scores and binding energies. In silico analysis predicted ADMET and physicochemical properties of the selected compounds and were used to assess their drug-likeness. Molecular dynamics (MD) simulation modelling methodology was also used to analyse the effectiveness and safety profile of selected bioactive chemicals based on the docking score, as well as to assess the stability of the MAPK6-ligand complex. Surprisingly, the discovered docking scores against MAPK6 revealed that the selected bioactive chemicals exhibit varying binding ability ranges between − 3.5 and − 10.6 kcal mol−1. MD simulation validated the stability of four chemicals at the MAPK6 binding pockets, including Assafoetidinol A (ASA), Naringin (NAR), Rutin (RUT), and Tomatine (TOM). According to the results obtained, fifty of the sixty-six compounds showed higher binding energy (− 6.1 to − 10.6 kcal mol−1), and four of these compounds may be used as lead compounds to protect cells against oxidative stress-induced human malignancies.

scholarly journals In-Silico Evaluation of Tiryaq-E-Wabai, an Unani Formulation for its Potency against SARS-CoV-2 Spike Glycoprotein and Main Protease

2021 ◽  
Vol 11 (4-S) ◽  
pp. 86-100
Author(s):  
N ZAHEER AHMED ◽  
DICKY JOHN DAVIS ◽  
NOMAN ANWAR ◽  
ASIM ALI KHAN ◽  
RAM PRATAP MEENA ◽  
...  
Keyword(s):  
In Silico ◽  
Dynamics Simulation ◽  
In Vivo Studies ◽  
Spike Glycoprotein ◽  
Unani Medicine ◽  
Main Protease ◽  
Pubchem Database ◽  
The Stability

COVID-19 was originated in Wuhan, China, in December 2019 and has been declared a pandemic disease by WHO. The number of infected cases continues unabated and so far, no specific drug approved for targeted therapy. Hence, there is a need for drug discovery from traditional medicine. Tiryaq-e-Wabai is a well-documented formulation in Unani medicine for its wide use as prophylaxis during epidemics of cholera, plague and other earlier epidemic diseases. The objective of the current study is to generate in-silico evidence and evaluate the potency of Tiryaq-e-Wabai against SARS-CoV-2 spike (S) glycoprotein and main protease (3CLpro). The structures of all phytocompounds used in this study were retrieved from PubChem database and some were built using Marvin Sketch. The protein structure of the SARS-CoV-2 S glycoprotein and 3CLpro was retrieved from the PDB ID: 6LZG and 7BQY respectively. AutoDock Vina was used to predict top ranking poses with best scores. The results of the molecular docking showed that phytocompounds of Tiryaq-e-Wabai exhibited good docking power with spike glycoprotein and 3CLpro. Among tested compounds Crocin from Zafran and Aloin A from Sibr showed strong binding to spike glycoprotein and 3CLpro respectively. Molecular dynamics simulation confirmed the stability of the S glycoprotein-Crocin and 3CLpro-Aloin A complexes. The Unani formulation Tiryaq-e-Wabai has great potential to inhibit the SARS-CoV-2, which have to be substantiated with further in-vitro and in-vivo studies. Keywords: In-silico study, SARS-CoV-2, Tiryaq-e-Wabai, Unani formulation, Crocin, Aloin A

Sign in / Sign up

Export Citation Format

Share Document