scholarly journals Designing a new multi epitope-based vaccine against COVID-19 disease: an immunoinformatic study based on reverse vaccinology approach

2021 ◽  
Author(s):  
Afshin Samimi Nemati ◽  
Majid Tafrihi ◽  
Fatemeh Sheikhi ◽  
Abolfazl Rostamian Tabari ◽  
Amirhossein Haditabar
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
High Rate ◽  
Effective Vaccine ◽  
Epitope Vaccine ◽  
Mhc I ◽  
Mhc Ii ◽  
Refinement Process

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has currently caused a significant pandemic among worldwide populations. The transmission speed and the high rate of mortality caused by the disease necessitate studies for the rapid designing and effective vaccine production. The purpose of this study is to predict and design a novel multi-epitope vaccine against the SARS-CoV-2 virus using bioinformatics approaches. Coronavirus envelope proteins, ORF7b, ORF8, ORF10, and NSP9 were selected as targets for epitope mapping using IEDB and BepiPred 2.0 Servers. Also, molecular docking studies were performed to determine the candidate vaccine's affinity to TLR3, TLR4, MHC I, and MHC II molecules. Thirteen epitopes were selected to construct the multi-epitope vaccine. We found that the constructed peptide has valuable antigenicity, stability, and appropriate half-life. The Ramachandran plot approved the quality of the predicted model after the refinement process. Molecular docking investigations revealed that antibody-mode in the Cluspro 2.0 server showed the lowest binding energy for MHCI, MHCII, TLR3, and TLR4. This study confirmed that the designed vaccine has a good antigenicity and stability and could be a proper vaccine candidate against the COVID-19 infectious disease though, in vitro and in vivo experiments are necessary to complete and confirm our results.

scholarly journals Hypoglycemic, hepatoprotective and molecular docking studies of 5-[(4-chlorophenoxy) methyl]-1, 3, 4-oxadiazole-2-thiol

2018 ◽  
Vol 13 (2) ◽  
pp. 149 ◽  
Author(s):  
Naureen Shehzadi ◽  
Khalid Hussain ◽  
Nadeem Irfan Bukhari ◽  
Muhammad Islam ◽  
Muhammad Tanveer Khan ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Video Clip ◽  
Serum Levels ◽  
Docking Studies ◽  
Normal Serum ◽  
Yeast Cells ◽  
Drug Candidate ◽  
Molecular Docking Studies

<p class="Abstract">The present study aimed at the evaluation of anti-hyperglycemic and hepatoprotective potential of a new drug candidate, 5-[(4-chlorophenoxy) methyl]-1,3,4-oxadiazole-2-thiol (OXCPM) through in vitro and in vivo assays, respectively. The compound displayed excellent dose-dependent ɑ-amylase (28.0-92.0%), ɑ-glucosidase (40.3-93.1%) and hemoglobin glycosylation (9.0%-54.9%) inhibitory effects and promoted the uptake of glucose by the yeast cells (0.2 to 26.3%). The treatment of the isoniazid- and rifampicin- (p.o., 50 mg/kg of each) intoxicated rats with OXCPM (100 mg/kg, p.o.) resulted in restoring the normal serum levels of the non-enzymatic (total bilirubin, total protein and albumin) and bringing about a remarkable decrease in the levels of enzymatic (alanine transaminases, aspartate transaminases and alkaline phosphatase) biomarkers. The molecular docking studies indicated high binding affinity of the compound for hyperglycemia-related protein targets; fructose-1,6-bisphosphatase, beta<sub>2</sub>-adrenergic receptors and glucokinase. The results indicate that OXCPM may not only reduce hyperglycemia by enzyme inhibition but also the disease complications through protection of hemoglobin glycosylation and hepatic injury.</p><p class="Abstract"><strong>Video Clip of Methodology:</strong></p><p class="Abstract">Glucose uptake by yeast cells:   4 min 51 sec   <a href="https://www.youtube.com/v/8cJkuMtV0Wc">Full Screen</a>   <a href="https://www.youtube.com/watch?v=8cJkuMtV0Wc">Alternate</a></p>

scholarly journals Effect of Harmine against Parkinson’s Disease Protein (PARK7) through Molecular Docking Studies

2021 ◽  
Vol 9 (VI) ◽  
pp. 5479-5485
Author(s):  
Love Kumar
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Docking ◽  
Neurodegenerative Disorder ◽  
Docking Studies ◽  
In Vivo Studies ◽  
Receptor Protein ◽  
Unknown Etiology

Parkinson’s disease (PD) is a common known neurodegenerative disorder with unknown etiology. It was estimated about 0.3% prevalence in the U.S population and enhance to 4 to 5% in older than 85 years. All studies were depending on the molecular docking where all ligands and protein PARK7 (PDB ID: 2RK3) were interacted by docked process. Some natural compounds was selected such as Harmine, Alloxan, Alpha spinasterol, Myrcene, and Vasicinone and PARK7 (PDB ID: 2RK3) protein. According to the PyRx and SWISS ADME result, Harmine was the only ligand which was showing minimum binding affinity. AutoDock Vina software was used for docking process between ligand (Harmine) and receptor protein PARK7 (PDB ID: 2RK3). The result was visualized under PyMol. Harmine was inhibiting the activity of PARK7 (PDB ID: 2RK3) and it may be used for the treatment of PD in future prospect after its in vitro and in vivo studies.

scholarly journals Design of Epitope-Based Peptide Vaccine against Pseudomonas aeruginosa Fructose Bisphosphate Aldolase Protein Using Immunoinformatics

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Mustafa Elhag ◽  
Ruaa Mohamed Alaagib ◽  
Nagla Mohamed Ahmed ◽  
Mustafa Abubaker ◽  
Esraa Musa Haroun ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Peptide Vaccine ◽  
Multidrug Resistant ◽  
Fructose Bisphosphate ◽  
Mhc I ◽  
Mhc Ii ◽  
Fructose Bisphosphate Aldolase ◽  
Hospital Acquired

Pseudomonas aeruginosa is a common pathogen that is responsible for serious hospital-acquired infections, ventilator-associated pneumonia, and various sepsis syndromes. Also, it is a multidrug-resistant pathogen recognized for its ubiquity and its intrinsically advanced antibiotic-resistant mechanisms. It usually affects immunocompromised individuals but can also infect immunocompetent individuals. There is no vaccine against it available till now. This study predicts an effective epitope-based vaccine against fructose bisphosphate aldolase (FBA) of Pseudomonas aeruginosa using immunoinformatics tools. The protein sequences were obtained from NCBI, and prediction tests were undertaken to analyze possible epitopes for B and T cells. Three B cell epitopes passed the antigenicity, accessibility, and hydrophilicity tests. Six MHC I epitopes were found to be promising, while four MHC II epitopes were found promising from the result set. Nineteen epitopes were shared between MHC I and II results. For the population coverage, the epitopes covered 95.62% worldwide excluding certain MHC II alleles. We recommend in vivo and in vitro studies to prove its effectiveness.

Evaluation of anti-diabetic and alpha glucosidase inhibitory action of anthraquinones from Rheum emodi

2015 ◽  
Vol 6 (8) ◽  
pp. 2693-2700 ◽  
Author(s):  
Aditya Arvindekar ◽  
Tanaji More ◽  
Pavan V. Payghan ◽  
Kirti Laddha ◽  
Nanda Ghoshal ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Inhibitory Action ◽  
Docking Studies ◽  
Molecular Docking Studies ◽  
Alpha Glucosidase

The 1,8-dihydroxyanthraquinones from the culinary and medicinally important plant Rheum emodi exert anti-hyperglycemic potential but notably different α-glucosidase actions as established by in vitro, in vivo, kinetics and molecular docking studies.

scholarly journals Comprehensive Analysis of Nef Functions Selected in Simian Immunodeficiency Virus-Infected Macaques

2004 ◽  
Vol 78 (19) ◽  
pp. 10588-10597 ◽  
Author(s):  
Michael Schindler ◽  
Jan Münch ◽  
Matthias Brenner ◽  
Christiane Stahl-Hennig ◽  
Jacek Skowronski ◽  
...  
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Rhesus Macaques ◽  
Surface Expression ◽  
Viral Fitness ◽  
Cell Surface Expression ◽  
Mhc I ◽  
Mhc Ii ◽  
Immunodeficiency Virus

ABSTRACT A variety of simian immunodeficiency virus (SIVmac) nef mutants have been investigated to clarify which in vitro Nef functions contribute to efficient viral replication and pathogenicity in rhesus macaques. Most of these nef alleles, however, were only functionally characterized for their ability to down-modulate CD4 and class I major histocompatibility complex (MHC-I) cell surface expression and to enhance SIV replication and infectivity. To obtain information on the in vivo relevance of more recently established Nef functions, we examined the ability of a large panel of constructed SIVmac Nef mutants and of variants that emerged in infected macaques to down-regulate CD3, CD28, and MHC-II and to up-regulate the MHC-II-associated invariant chain (Ii). We found that all these four Nef functions were restored in SIV-infected macaques. In most cases, however, the initial mutations and the changes selected in vivo affected several in vitro Nef functions. For example, truncated Nef proteins that emerged in animals infected with SIVmac239 containing a 152-bp deletion in nef efficiently modulated both CD3 and Ii surface expression. Overall, our results suggest that the effect of Nef on each of the six cellular receptors investigated contributes to viral fitness in the infected host but also indicate that modulation of CD3, MHC-I, MHC-II, or Ii surface expression alone is insufficient for SIV virulence.

scholarly journals Phloroglucinol as a Potential Candidate against Trypanosoma congolense Infection: Insights from In Vivo, In Vitro, Molecular Docking and Molecular Dynamic Simulation Analyses

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 469
Author(s):  
Nasirudeen Idowu Abdulrashid ◽  
Suleiman Aminu ◽  
Rahma Muhammad Adamu ◽  
Nasir Tajuddeen ◽  
Murtala Bindawa Isah ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
Binding Energies ◽  
Sub Saharan Africa ◽  
Dynamics Simulation ◽  
Potential Candidate ◽  
Inhibitory Effects ◽  
Hydrogen Bond Interaction

Sub-Saharan Africa is profoundly challenged with African Animal Trypanosomiasis and the available trypanocides are faced with drawbacks, necessitating the search for novel agents. Herein, the chemotherapeutic potential of phloroglucinol on T. congolense infection and its inhibitory effects on the partially purified T. congolense sialidase and phospholipase A2 (PLA2) were investigated. Treatment with phloroglucinol for 14 days significantly (p < 0.05) suppressed T. congolense proliferation, increased animal survival and ameliorated anemia induced by the parasite. Using biochemical and histopathological analyses, phloroglucinol was found to prevent renal damages and splenomegaly, besides its protection against T. congolense-associated increase in free serum sialic acids in infected animals. Moreover, the compound inhibited bloodstream T. congolense sialidase via mixed inhibition pattern with inhibition binding constant (Ki) of 0.181 µM, but a very low uncompetitive inhibitory effects against PLA2 (Ki > 9000 µM) was recorded. Molecular docking studies revealed binding energies of −4.9 and −5.3 kcal/mol between phloroglucinol with modeled sialidase and PLA2 respectively, while a 50 ns molecular dynamics simulation using GROMACS revealed the sialidase-phloroglucinol complex to be more compact and stable with higher free binding energy (−67.84 ± 0.50 kJ/mol) than PLA2-phloroglucinol complex (−77.17 ± 0.52 kJ/mol), based on MM-PBSA analysis. The sialidase-phloroglucinol complex had a single hydrogen bond interaction with Ser453 while none was observed for the PLA2-phloroglucinol complex. In conclusion, phloroglucinol showed moderate trypanostatic activity with great potential in ameliorating some of the parasite-induced pathologies and its anti-anemic effects might be linked to inhibition of sialidase rather than PLA2.

scholarly journals A Multiple Peptides Vaccine against nCOVID-19 Designed from the Nucleocapsid phosphoprotein (N) and Spike Glycoprotein (S) via the Immunoinformatics Approach

2020 ◽  
Author(s):  
Sahar Obi Abd Albagi ◽  
Mosab Yahya Al-Nour ◽  
Mustafa Elhag ◽  
Asaad Tageldein Idris Abdelihalim ◽  
Esraa Musa Haroun ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Effective Vaccine ◽  
Spike Glycoprotein ◽  
Mhc I ◽  
Immunological Responses ◽  
Mhc Ii ◽  
Immune Epitope ◽  
Hla Dqa1 ◽  
Immune Epitope Database

AbstractDue to the current COVID-19 pandemic, the rapid discovery of a safe and effective vaccine is an essential issue, consequently, this study aims to predict potential COVID-19 peptide-based vaccine utilizing the Nucleocapsid phosphoprotein (N) and Spike Glycoprotein (S) via the Immunoinformatics approach. To achieve this goal, several Immune Epitope Database (IEDB) tools, molecular docking, and safety prediction servers were used. According to the results, The Spike peptide peptides SQCVNLTTRTQLPPAYTNSFTRGVY is predicted to have the highest binding affinity to the B-Cells. The Spike peptide FTISVTTEI has the highest binding affinity to the MHC I HLA-B1503 allele. The Nucleocapsid peptides KTFPPTEPK and RWYFYYLGTGPEAGL have the highest binding affinity to the MHC I HLA-A0202 allele and the three MHC II alleles HLA-DPA1*01:03/DPB1*02:01, HLA-DQA1*01:02/DQB1- *06:02, HLA-DRB1, respectively. Furthermore, those peptides were predicted as non-toxic and non-allergen. Therefore, the combination of those peptides is predicted to stimulate better immunological responses with respectable safety.

Potential Bioactive glycosylated flavonoids as SARS-CoV-2 Main protease Inhibitors: A molecular Docking Study

2020 ◽  
Author(s):  
sabri ahmed cherrak ◽  
merzouk hafida ◽  
mokhtari soulimane nassima
Keyword(s):  
Molecular Docking ◽  
Data Bank ◽  
Docking Study ◽  
Docking Studies ◽  
Molecular Docking Study ◽  
Chemical Structures ◽  
In Vivo Experiments ◽  
Main Protease

A novel (COVID-19) responsible of acute respiratory infection closely related to SARS-CoV has recently emerged. So far there is no consensus for drug treatment to stop the spread of the virus. Discovery of a drug that would limit the virus expansion is one of the biggest challenges faced by the humanity in the last decades. In this perspective, testing existing drugs as inhibitors of the main COVID-19 protease is a good approach.Among natural phenolic compounds found in plants, fruit, and vegetables; flavonoids are the most abundant. Flavonoids, especially in their glycosylated forms, display a number of physiological activities, which makes them interesting to investigate as antiviral molecules.The flavonoids chemical structures were downloaded from PubChem and protease structure 6lu7 was from the Protein Data Bank site. Molecular docking study was performed using AutoDock Vina. Among the tested molecules Quercetin-3-O-rhamnoside showed the highest binding affinity (-9,7 kcal/mol). Docking studies showed that glycosylated flavonoids are good inhibitors for the covid-19 protease and could be further investigated by in vitro and in vivo experiments for further validation.

scholarly journals In Silico Identification of New Targets for Diagnosis, Vaccine, and Drug Candidates against Trypanosoma cruzi

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Rafael Obata Trevisan ◽  
Malú Mateus Santos ◽  
Chamberttan Souza Desidério ◽  
Leandro Gomes Alves ◽  
Thiago de Jesus Sousa ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Drug Targets ◽  
Hot Spot ◽  
Mhc I ◽  
Drug Candidates ◽  
Subtractive Genomics

Chagas disease is a neglected tropical disease caused by the parasite Trypanosoma cruzi. Despite the efforts and distinct methodologies, the search of antigens for diagnosis, vaccine, and drug targets for the disease is still needed. The present study is aimed at identifying possible antigens that could be used for diagnosis, vaccine, and drugs targets against T. cruzi using reverse vaccinology and molecular docking. The genomes of 28 T. cruzi strains available in GenBank (NCBI) were used to obtain the genomic core. Then, subtractive genomics was carried out to identify nonhomologous genes to the host in the core. A total of 2630 conserved proteins in 28 strains of T. cruzi were predicted using OrthoFinder and Diamond software, in which 515 showed no homology to the human host. These proteins were evaluated for their subcellular localization, from which 214 are cytoplasmic and 117 are secreted or present in the plasma membrane. To identify the antigens for diagnosis and vaccine targets, we used the VaxiJen software, and 14 nonhomologous proteins were selected showing high binding efficiency with MHC I and MHC II with potential for in vitro and in vivo tests. When these 14 nonhomologous molecules were compared against other trypanosomatids, it was found that the retrotransposon hot spot (RHS) protein is specific only for T. cruzi parasite suggesting that it could be used for Chagas diagnosis. Such 14 proteins were analyzed using the IEDB software to predict their epitopes in both B and T lymphocytes. Furthermore, molecular docking analysis was performed using the software MHOLline. As a result, we identified 6 possible T. cruzi drug targets that could interact with 4 compounds already known as antiparasitic activities. These 14 protein targets, along with 6 potential drug candidates, can be further validated in future studies, in vivo, regarding Chagas disease.

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