scholarly journals Targeting SARS-CoV-2 nonstructural protein 15 endoribonuclease: an in silico perspective

2021 ◽  
Author(s):  
Shafi Mahmud ◽  
Abdo A Elfiky ◽  
Al Amin ◽  
Sumon Chandro Mohanto ◽  
Ekhtiar Rahman ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
In Silico ◽  
Nonstructural Protein ◽  
Pharmacological Properties ◽  
Binding Pattern ◽  
Human Coronavirus ◽  
Nonbonded Interactions ◽  
Active Site Cavity ◽  
Approved Drugs

The newly emerged human coronavirus, SARS-CoV-2, had begun to spread last year and sparked worldwide. In this study, molecular docking is utilized to test some previously approved drugs against the SARS-CoV-2 nonstructural protein 15 (Nsp15). We screened 23 drugs, from which three (saquinavir, valrubicin and aprepitant) show a paramount predicted binding affinity (-9.1, -9.6 and -9.2 kcal/mol, respectively) against SARS-CoV-2 Nsp15. Moreover, saquinavir and aprepitant make nonbonded interactions with Leu201 in the active site cavity of Nsp15, while the drug valrubicin interacts with Arg199 and Leu201. This binding pattern may be effective against the targeted protein, leading to Nsp15 blockage and virus abolition. Additionally, the pharmacological properties of the screened drugs are known since they have been approved against different viruses.

scholarly journals Mulberrofuran G, a Potent Inhibitor of SPIKE Protein of SARS Corona Virus 2

2021 ◽  
Author(s):  
Fatemeh Sadat Hosseini ◽  
Mohammad Reza Motamedi
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
Active Site ◽  
Potential Role ◽  
Potent Inhibitor ◽  
Screening Method ◽  
Spike Protein ◽  
Treatment Agent ◽  
Approved Drugs ◽  
Fda Approved Drugs

Background: At the onset of the 2020 year, Coronavirus disease (COVID-19) has become a pandemic and infected many people worldwide. Despite all efforts, no cure was found for this infection. Bioinformatics and medicinal chemistry have a potential role in the primary consideration of drugs to treat this infection. With virtual screening and molecular docking, some potent compounds and medications can be found and modified and then applied to treat disease in the next steps. Methods: By virtual screening method and PRYX software, some Food and Drug Administration (FDA) approved drugs and natural compounds have been docked with the SPIKE protein of SARS-CoV-2. Some more potent agents have been selected, and then new structures are designed with better affinity than them. After that, we searched for the molecules with a similar structure to designed compounds to find the most potent compound to our target. Results: Because of the study of structures and affinities, mulberrofuran G was the most potent compound in this study. The compound has interacted strongly with residues in the probably active site of SPIKE. Conclusion: Mulberrofuran G can be a treatment agent candidate for COVID-19 because of its good affinity to SPIKE of the virus and inhibition of virus-cell adhesion and entrance.

scholarly journals Molecular docking and pharmacokinetic screening of eucalyptol (1,8 cineole) from eucalyptus essential oil against SARS-CoV-2

2020 ◽  
Vol 12 (3) ◽  
pp. 536-545
Author(s):  
Arun D. SHARMA ◽  
Inderjeet KAUR
Keyword(s):  
Molecular Docking ◽  
Essential Oil ◽  
Active Site ◽  
In Silico ◽  
Hydrophobic Interactions ◽  
Rna Virus ◽  
In Silico Analysis ◽  
Active Site Residues ◽  
Virus Family

SARS-CoV-2 (COVID-19), member of corona virus family, is a positive single stranded RNA virus. Due to lack of drugs it is spreading its tentacles across the world. Being associated with cough, fever, and respiratory distress, this disease caused more than 15% mortality worldwide. Mpro/3CLpro has recently been regarded as a suitable target for drug design due to its vital role in virus replication. The current study focused on the inhibitory activity of eucalyptol (1,8 cineole), an essential oil component from eucalyptus oil, against Mpro/3CLprofrom SARS-CoV-2. Till date there is no work is undertaken on in-silico analysis of this compound against Mpro/3CLproof SARS-CoV-2. Molecular docking studies were conducted by using 1-click dock tool and Patchdock analysis. In-silico absorption, distribution, metabolism, excretion and toxicity (ADMET) profile were also studied. The calculated parameters such as docking score indicated effective binding of eucalyptol to COVID-19 Mpro protein. Active site prediction revealed the involvement of active site residues in ligand binding. Interactions results indicated that, Mpro/3CLpro/eucalyptol complexes forms hydrophobic interactions. ADMET studies provided guidelines and mechanistic scope for identification of potent anti-COVID 19 drug. Therefore, eucalyptol may represent potential herbal treatment to act as COVID-19 Mpro/3CLproinhibitor, a finding which must be validated in vivo.

scholarly journals In silico evaluation of some 4-(quinolin-2-yl)pyrimidin-2-amine derivatives as potent V600E-BRAF inhibitors with pharmacokinetics ADMET and drug-likeness predictions

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Abdullahi Bello Umar ◽  
Adamu Uzairu ◽  
Gideon Adamu Shallangwa ◽  
Sani Uba
Keyword(s):  
Molecular Docking ◽  
Side Effects ◽  
Oral Bioavailability ◽  
In Silico ◽  
Braf Inhibitor ◽  
Docking Studies ◽  
Pharmacological Properties ◽  
Braf Inhibitors ◽  
Docking Analysis ◽  
Risk Parameters

Abstract Background The resistance of V600E-BRAF to the vemurafenib and the side effects of the identified inhibitors trigger the research for a novel and more potent anti-melanoma agents. In this study, virtual docking screening along with pharmacokinetics ADMET and drug-likeness predictions were combined to evaluate some 4-(quinolin-2-yl)pyrimidin-2-amine derivatives as potent V600E-BRAF inhibitors. Results Some of the selected compounds exhibited better binding scores and favorable interaction with the V600E-BRAF enzyme. Out of the screened compounds, two most potent (5 and 9) having good Rerank scores (− 128.011 and − 126.258) emerged as effective and potent V600E-BRAF inhibitors that outperformed the FDA-approved V600E-BRAF inhibitor (vemurafenib, − 118.607). Thus, the molecular docking studies revealed that the studied compounds showed competing for inhibition of V600E-BRAF with vemurafenib at the binding site and possessed better pharmacological parameters based on the drug-likeness rules filters for the oral bioavailability, and ADMET risk parameters. Conclusion The docking analysis, drug-likeness rules filters, and ADMET study identified compounds (5 and 9) as the best hits against V600E-BRAF kinase with enhanced pharmacological properties. This recommends that these compounds may be developed as potent anti-melanoma agents.

scholarly journals In Silico Pharmacophore Study and Structural Optimization of Nafamostat Yield Potentially Novel Transmembrane Protease Serine 2 (TMPRSS2) Inhibitors Which Block the Entry of SARS-CoV-2 Virus into Human Cells

2020 ◽  
Author(s):  
Bach Nguyen
Keyword(s):  
Molecular Docking ◽  
Structural Optimization ◽  
Small Molecules ◽  
In Silico ◽  
Host Cells ◽  
The Past ◽  
Anticoagulant Drug ◽  
Approved Drugs ◽  
Transmembrane Serine Protease ◽  
Nafamostat Mesylate

<p></p><p>The past 6 months since December 2019 were marked by the COVID-19 pandemic caused from the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to the urgent state worldwide, many efforts have been directed on repurposing approved drugs to facilitate the discovery of effective therapies. In this work, I employ molecular docking (<i>in silico</i>) as an approach to study the intermolecular interactions between Nafamostat mesylate – an approved anticoagulant drug, and transmembrane serine protease 2 (TMPRSS2) which is crucial for coronaviruses to enter host cells. Furthermore, structural optimization of Nafamostat is performed using pharmacophoric approach which indicates some small molecules as potentially effective TMPRSS2 inhibitors and pharmaceutical candidates for COVID-19 pandemic.</p><br><p></p>

In silico Molecular Docking and ADME Studies of 1,3,4-Thiadiazole Derivatives in Relation to in vitro PON1 Activity

2019 ◽  
Vol 15 (2) ◽  
pp. 136-144
Author(s):  
Belgin Sever ◽  
Kaan Kucukoglu ◽  
Hayrunnisa Nadaroglu ◽  
Mehlika Dilek Altıntop
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
In Silico ◽  
Oxidative Modification ◽  
Paraoxonase 1 ◽  
Therapeutic Effects ◽  
Acetophenone Derivatives ◽  
Thiadiazole Derivatives ◽  
In Silico Molecular Docking

Background: Paraoxonase 1 (PON1) is a paraoxonase, arylesterase and lactonase associated with protection of lipoproteins and cell membranes against oxidative modification. Objective: Based on antioxidative properties of PON1 and significance of 1,3,4-thiadiazoles in pharmaceutical chemistry, herein we aimed to evaluate the potentials of 1,3,4-thiadiazole derivatives as PON1 activators. Methods: 2-[[5-(2,4-Difluoro/dichlorophenylamino)-1,3,4-thiadiazol-2-yl]thio]acetophenone derivatives (1-18) were in vitro evaluated for their activator effects on PON1 which was purified using ammonium sulfate precipitation (60-80%) and DEAE-Sephadex anion exchange chromatography. Molecular docking studies were performed for the detection of affinities of all compounds to the active site of PON1. Moreover, Absorption, Distribution, Metabolism and Excretion (ADME) properties of all compounds were also in silico predicted. In silico molecular docking and ADME studies were carried out according to modules of Schrodinger’s Maestro molecular modeling package. Results: All compounds, particularly compounds 10, 13 and 17, were determined as promising PON1 activators and apart from compound 1, all of them were detected in the active site of PON1. Besides, ADME results indicated that all compounds were potential orally bioavailable drug-like molecules. Conclusion: PON1 activators, compounds 10, 13 and 17 stand out as potential drug candidates for further antioxidant studies and these compounds can be investigated for their therapeutic effects in many disorders such as atherosclerosis, diabetes mellitus, obesity, chronic liver inflammation and many more.

scholarly journals Activity Prediction of Bioactive Compounds Contained in Etlingera elatior Against the SARS-CoV-2 Main Protease: An In Silico Approach

2020 ◽  
Vol 3 (4) ◽  
pp. 235-242
Author(s):  
Dwi Syah Fitra Ramadhan ◽  
Taufik Muhammad Fakih ◽  
Arfan Arfan
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
In Silico ◽  
Biological Activities ◽  
Activity Prediction ◽  
Ergosterol Peroxide ◽  
Main Protease ◽  
Promising Therapeutic Target ◽  
In Silico Methods ◽  
Etlingera Elatior

The COVID-19 pandemic has become a serious problem today, with its prevalence increasing every day. The SARS-CoV-2 main protease (MPro) is a promising therapeutic target to inhibit replicating and spreading the virus that causes COVID-19. The compounds contained in the Etlingera elatior plant has the potential. This study aimed to examine the compounds' activity in E. elatior against SARS-CoV-2 MPro using in silico methods. A total of seven compounds contained in E. elatior were obtained from the Knapsack database. The compounds were then docked into the SARS-CoV-2 MPro receptor's active site with the PDB ID 6LU7. Afterward, the biological activities were predicted by the PASS prediction webserver. The molecular docking results showed that ergosterol peroxide and sitostenone had the best binding energy with -10.40 kcal/mol and -9.17 kcal/mol, respectively. The in silico PASS prediction showed it has potential as antiviral therapy. It concluded ergosterol peroxide and sitostenone has the potential as SARS-CoV-2 MPro inhibitor candidate.

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 Identifikasi Aktivitas Inhibitor Enzim Tirosinase Senyawa Turunan Flavonoid pada Kulit Buah Cokelat (Theobroma cacao L) secara In Silico

2021 ◽  
Vol 17 (2) ◽  
pp. 168
Author(s):  
Sani Ega Priani ◽  
Taufik Muhammad Fakih
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Active Site ◽  
In Silico ◽  
Background Color ◽  
White Space ◽  
Font Size ◽  
Flavonoid Compounds ◽  
Normal Text ◽  
Cocoa Pod Husk

<p id="docs-internal-guid-fa145b0a-7fff-0af1-a074-1cbfd7cb8daf" style="line-height: 1.2; margin-left: 0.35pt; margin-right: -0.1pt; text-align: justify; margin-top: 6pt; margin-bottom: 6pt;" dir="ltr"><span style="font-size: 8.5pt; font-family: 'Times New Roman'; color: #000000; background-color: transparent; font-weight: 400; font-style: normal; font-variant: normal; text-decoration: none; vertical-align: baseline; white-space: pre-wrap;">Limbah kulit buah cokelat diketahui mengandung berbagai senyawa aktif, termasuk di antaranya adalah golongan flavonoid. Senyawa flavonoid diketahui berpotensi memiliki aktivitas inhibitor enzim tirosinase, suatu enzim yang menstimulasi proses pembentukan melanin. Penelitian ini bertujuan untuk mengevaluasi interaksi antara senyawa flavonoid dari kulit buah cokelat dengan enzim tirosinase menggunakan metode penambatan molekuler secara </span><span style="font-size: 8.5pt; font-family: 'Times New Roman'; color: #000000; background-color: transparent; font-weight: 400; font-style: italic; font-variant: normal; text-decoration: none; vertical-align: baseline; white-space: pre-wrap;">in silico</span><span style="font-size: 8.5pt; font-family: 'Times New Roman'; color: #000000; background-color: transparent; font-weight: 400; font-style: normal; font-variant: normal; text-decoration: none; vertical-align: baseline; white-space: pre-wrap;">. Pengujian dilakukan dengan beberapa tahapan yakni preparasi makromolekul enzim, pemodelan molekul senyawa uji, identifikasi sisi aktif molekul enzim, identifikasi dan evaluasi penambatan molekuler, serta simulasi dinamika molekuler senyawa uji dengan molekul enzim. Hasil simulasi penambatan molekuler antara molekul enzim dengan ligan alaminya yakni tirosin memberikan energi ikatan sebesar -4,91 kkal/mol. Senyawa flavonoid dari kulit buah cokelat yakni apigenin, epikatekin, katekin, kaemferol, kuersetin, dan kuersitrin  diketahui memiliki afinitas pada sisi aktif enzim tirosinase dengan energi ikatan berturut turut -6,14; -6,17; -6,01; -5,89; -6,13; -6,81 kkal/mol. Hasil simulasi dinamika molekuler menunjukkan kuersitrin memiliki stabilitas yang baik dengan nilai RMSD rata-rata dan nilai energi bebas ikatan MM/PBSA masing-masing sebesar ±1,73 Å dan -80,12 kJ/mol. Hasil penelitian menunjukkan bahwa senyawa turunan flavonoid tersebut mampu berikatan dengan sisi aktif enzim tirosinase dengan afinitas yang lebih baik dibandingkan dengan ligan alaminya diamati dari nilai energi ikatannya. Senyawa turunan flavonoid yang terkandung dalam kulit buah cokelat berpotensi menjadi inhibitor kompetitif dari enzim tirosinase.</span></p><p style="line-height: 1.2; margin-left: 0.35pt; margin-right: -0.1pt; text-align: justify; margin-top: 6pt; margin-bottom: 6pt;" dir="ltr"><span style="font-size: 8.5pt; font-family: 'Times New Roman'; color: #000000; background-color: transparent; font-weight: 400; font-style: normal; font-variant: normal; text-decoration: none; vertical-align: baseline; white-space: pre-wrap;"><strong><span id="docs-internal-guid-99cc03b4-7fff-2cb3-0bd8-cbf26c857d04" style="font-size: 8.5pt; font-family: 'Times New Roman'; color: #000000; background-color: transparent; font-style: normal; font-variant: normal; text-decoration: none; vertical-align: baseline; white-space: pre-wrap;">Identification of In Silico Tyrosinase Inhibitory Activity of Flavonoid Derivative Compounds in Cocoa Pod Husk (</span><span style="font-size: 8.5pt; font-family: 'Times New Roman'; color: #000000; background-color: transparent; font-style: italic; font-variant: normal; text-decoration: none; vertical-align: baseline; white-space: pre-wrap;">Theobroma cacao </span><span style="font-size: 8.5pt; font-family: 'Times New Roman'; color: #000000; background-color: transparent; font-style: normal; font-variant: normal; text-decoration: none; vertical-align: baseline; white-space: pre-wrap;">L.). </span></strong><span style="font-size: 8.5pt; font-family: 'Times New Roman'; color: #000000; background-color: transparent; font-weight: 400; font-style: normal; font-variant: normal; text-decoration: none; vertical-align: baseline; white-space: pre-wrap;">Cocoa pod husk was known to contain several active compounds, such as flavonoids. Flavonoid compounds are known to potentially have inhibitory activity of the tyrosinase, the enzyme which stimulates melanin synthesis.</span><span style="font-size: 8.5pt; font-family: 'Times New Roman'; color: #000000; background-color: transparent; font-weight: 400; font-style: normal; font-variant: normal; text-decoration: none; vertical-align: baseline; white-space: pre-wrap;">This study was conducted to evaluate the molecular interaction between flavonoids from cocoa pod husk with tyrosinase enzyme using in silico molecular docking method. The study was carried out through several stages, including preparation of enzyme macromolecules, modeling the molecule of the test compound, identifying the active site of the enzyme molecule, identifying and evaluating molecular docking, and molecular dynamics simulations of the test compound with the enzyme molecule. Molecular docking simulation between the enzyme and its natural ligand (tyrosine) produces binding energy of -4.91 kcal/mol. Flavonoid compounds from cocoa pod husk, including apigenin, epicatechin, catechin, kaempferol, quercetin, dan quercitrin, have an affinity on the active site of the enzyme with binding energy were -6.14; -6.17; -6.01; -5.89; -6.13; -6.81 kcal/mol, respectively. Then the molecular dynamics simulation shows quercitrin has good stability interaction with the average RMSD value and the MM/PBSA binding-free energy values of ±1.73 Å and -80.12 kJ/mol, respectively. The results showed that flavonoids of cocoa pod husc extract have an affinity to the active site of the enzyme, with a stronger binding energy than the original ligand. The flavonoid compounds of cocoa pod husk potential as a competitive inhibitor of the tyrosinase enzyme.</span></span></p>

scholarly journals In silico study of anthocyanin and ternatin flavonoids for the treatment of inflammation-related diseases using molecular docking analysis

Food Research ◽  
2020 ◽  
Vol 4 (3) ◽  
pp. 780-785
Author(s):  
Y.T. Wijaya ◽  
A. Yulandi ◽  
A.W. Gunawan ◽  
Yanti
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Active Site ◽  
In Silico ◽  
Protein Crystal ◽  
Drug Candidate ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

Inflammatory markers such as cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), myeloperoxidase (MPO), and prostaglandin (PEG) are widely known as major targets in discovering natural anti-inflammatory drugs for the treatment of inflammationrelated diseases. Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and aspirin are mostly used at present, however, some NSAIDS have been reported to cause gastrointestinal side effect due to ligand-protein interaction. Molecular docking is a promising tool to study such modes of interaction. In this study, we evaluated the potential use of anthocyanin and ternatin flavonoids as natural anti-inflammatory agents for treatment of inflammatory-related diseases using in silico molecular docking assay. Automated docking study using Protein-Ligand ANT System (PLANTS) and AutoDock Vina was performed with various ligand molecules, including ibuprofen, anthocyanin, and ternatin against the protein crystal structures of COX-1, COX-2, iNOS, and MPO. The in silico data demonstrated that ibuprofen bound effectively to the active site of COX-1 and MPO with minimum binding energy, yet the compound required more energy to bind the active site of COX-2. Ternatin flavonoid was bound to COX-2 and iNOS with minimum binding energy. In terms of binding energy, anthocyanin flavonoid was found to be effective for inhibiting COX-1, COX-2, and iNOS. These results suggested that anthocyanin and ternatin flavonoids may potentially be developed as anti-inflammatory drug candidate for the treatment of inflammatory-related diseases.

scholarly journals In Silico Pharmacophore Study and Structural Optimization of Nafamostat Yield Potentially Novel Transmembrane Protease Serine 2 (TMPRSS2) Inhibitors Which Block the Entry of SARS-CoV-2 Virus into Human Cells

2020 ◽  
Author(s):  
Bach Nguyen
Keyword(s):  
Molecular Docking ◽  
Structural Optimization ◽  
Small Molecules ◽  
In Silico ◽  
Host Cells ◽  
The Past ◽  
Anticoagulant Drug ◽  
Approved Drugs ◽  
Transmembrane Serine Protease ◽  
Nafamostat Mesylate

<p></p><p>The past 6 months since December 2019 were marked by the COVID-19 pandemic caused from the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to the urgent state worldwide, many efforts have been directed on repurposing approved drugs to facilitate the discovery of effective therapies. In this work, I employ molecular docking (<i>in silico</i>) as an approach to study the intermolecular interactions between Nafamostat mesylate – an approved anticoagulant drug, and transmembrane serine protease 2 (TMPRSS2) which is crucial for coronaviruses to enter host cells. Furthermore, structural optimization of Nafamostat is performed using pharmacophoric approach which indicates some small molecules as potentially effective TMPRSS2 inhibitors and pharmaceutical candidates for COVID-19 pandemic.</p><br><p></p>

Sign in / Sign up

Export Citation Format

Share Document