Virtual Screening for the Identification of Potential Candidate Molecules Against Envelope (E) and Membrane (M) Proteins of SARS-CoV-2

2020 ◽  
pp. 2150008
Author(s):  
Abbas Alibakhshi ◽  
Mohammad Mehdi Ranjbar ◽  
Shaghayegh Haghjooy Javanmard ◽  
Fatemeh Yarian ◽  
Shahrzad Ahangarzadeh
Keyword(s):  
Md Simulation ◽  
Structural Proteins ◽  
Potential Candidate ◽  
Therapeutic Approaches ◽  
E Proteins ◽  
Virus Life Cycle ◽  
M Proteins ◽  
The World ◽  
Collective Motions ◽  
The Stability

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes COVID-19, a disease currently spreading around the world. Some drugs are underway or being used to combat this disease. Several proteins of the virus can be targeted in therapeutic approaches. Two structural proteins, membrane (M), envelope (E) have critical roles in virus life cycle, such as assembly, budding, envelope formation and pathogenesis. Here, we employed the in silico strategies to identify and evaluate the selected potential compounds against M and E proteins. For this, the structures of proteins were modeled and then several groups of compounds as FDA approved, natural products or under clinical trials were screened from DrugBank and ZINC databases. The selected dockings were analyzed and the ligands with best binding affinity scores were subjected to evaluate drug-likeness and medicinal chemistry friendliness through prediction of ADMET properties. Normal mode analyses were also performed for six selected complexes to explore the collective motions of proteins. Molecular dynamic (MD) simulation was also performed to calculate the stability of two docked protein–ligand complexes. The results revealed that several compounds had high affinity to the proteins along with some acceptable profiles of mobility and deformability, especially, for M protein.

scholarly journals Mutations in structural proteins of SARS-CoV-2 and potential implications for the ongoing outbreak of infection in India

2020 ◽  
Author(s):  
Rimjhim Dasgupta
Keyword(s):  
Structural Proteins ◽  
Significant Implication ◽  
Amino Acid Residues ◽  
Virus Propagation ◽  
Diagnostic Assays ◽  
Genetic Modifications ◽  
M Proteins ◽  
Substitution Mutations ◽  
The Stability ◽  
Multiple Substitution

SARS-CoV-2 has spread in India very quickly from its first reported case on 30 January 2020 in Thrissur, Kerala. With the drastic increasing number of positive cases around the world WHO raised the importance in the assessment of the risk of spread and understanding genetic modifications that could have occurred in the SARS-CoV-2. Using available genome sequence in NCBI repository from the samples of different locations in India, we identified the regions (hotspots) of the viral genome with high rates of mutation. We analysed four regions of the genome encoding structural proteins Spike (S), Nucleocapsid (N), envelop (E) and Membrane (M) proteins. Through computational biology approach, we identified multiple substitution mutations in S and N proteins whereas there is only one substitution in E protein and none in M protein.  We showed most of these amino acid residues are evolutionary conserved. The changes in the conserved residues may have significant implication on the stability of the proteins and subsequent interaction with other elements, which are essential for virus propagation. This provides a basis for a better understanding of the genetic variation in SARS-CoV-2 circulating in the India, which might provide important clues for identifying potential therapeutic targets, development of efficient vaccines, antiviral drugs and diagnostic assays for controlling COVID-19.

scholarly journals Plausible fast & economic detection of SARS-CoV infection using paper-based isoelectric focusing: a hypothesis

2020 ◽  
Author(s):  
Arindam Kushagra
Keyword(s):  
Isoelectric Focusing ◽  
Current Method ◽  
Structural Proteins ◽  
Infected Person ◽  
E Proteins ◽  
Severe Respiratory Distress ◽  
M Proteins ◽  
Isoelectric Points ◽  
Fast Pace ◽  
To Come

In the wake of current pandemic of COVID-19, there has arisen an urgent need to come up with novel ways to detect the infected person with SARS-CoV-2 at an extremely fast pace so that the person is immediately quarantined to prevent further transmission of the virus to other susceptible individuals. Such quick detection measures would allow the timely mitigation of the dreadful disease which has claimed close to 100,000 lives worldwide. In this article, a very fast and cheap way to detect the presence of SARS-CoV in the biopsied tissue has been proposed. The current method discussed here would drastically reduce the time of detection of an infected person to less than ~ 6 hours in addition to the economic benefit of using paper-based isoelectric focusing. The infecting coronavirus that causes severe respiratory distress contains four major types of structural proteins: spike (S) proteins, membrane (M) proteins, envelope (E) proteins & nucleocapsid (N) proteins. Peculiar isoelectric points of these four structural proteins have been proposed to detect the SARS-CoV infection. This work would be of immense interest to the scientists, researchers as well as health professionals who are trying to mitigate the spread of the disease as well as to cure it at the same time.

scholarly journals A study on non-synonymous mutational patterns in structural proteins of SARS-CoV-2

Genome ◽  
2021 ◽  
Author(s):  
Jayanta Kumar Das ◽  
Swarup Roy
Keyword(s):  
Host Adaptation ◽  
Biochemical Properties ◽  
Structural Proteins ◽  
Deleterious Mutations ◽  
Fusion Peptides ◽  
Structural Protein ◽  
N Protein ◽  
M Proteins ◽  
The World ◽  
Infection Biology

SARS-CoV-2 is mutating and creating divergent variants across the world. An in-depth investigation of the amino acid substitutions in the genomic signature of SARS-CoV-2 proteins is highly essential for understanding its host adaptation and infection biology. A total of 9587 SARS-CoV-2 structural protein sequences collected from 49 different countries are used to characterize protein-wise variants, substitution patterns (type and location), and major substitution changes. The majority of the substitutions are distinct, mostly in a particular location, and leads to a change in amino acid's biochemical properties. In terms of mutational changes, Envelope (E) and Membrane (M) proteins are relatively stable than Nucleocapsid (N) and Spike (S) proteins. Several co-occurrence substitutions are observed, particularly in S and N proteins. Substitution specific to active sub-domains reveals that Heptapeptide Repeat, Fusion peptides, Transmembrane in S protein, and N-terminal and C-terminal domains in N protein are remarkably mutated. We also observe a few deleterious mutations in the above domains. The overall study on non-synonymous mutation in structural proteins of SARS-CoV-2 at early in the pandemic indicates a diversity amongst virus sequences.

scholarly journals Immunoinformatics approach for multi-epitope vaccine design against structural proteins and ORF1a polyprotein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Khalid Mohamed Adam
Keyword(s):  
Plasmid Vector ◽  
Amino Acid Sequences ◽  
M Protein ◽  
Structural Proteins ◽  
Potential Candidate ◽  
E Proteins ◽  
S Protein ◽  
N Protein ◽  
Global Health Issue ◽  
Chimeric Construct

Abstract Background The lack of effective treatment against the highly infectious SARS-CoV-2 has aggravated the already catastrophic global health issue. Here, in an attempt to design an efficient vaccine, a thorough immunoinformatics approach was followed to predict the most suitable viral proteins epitopes for building that vaccine. Methods The amino acid sequences of four structural proteins (S, M, N, E) along with one potentially antigenic accessory protein (ORF1a) of SARS-CoV-2 were inspected for the most appropriate epitopes to be used for building the vaccine construct. Several immunoinformatics tools were used to assess the antigenicity (VaxiJen server), immunogenicity (IEDB immunogenicity tool), allergenicity (AlgPred), toxigenicity (ToxinPred server), interferon-gamma inducing capacity (IFNepitope server), and the physicochemical properties of the construct (ProtParam tool). Results The final candidate vaccine construct consisted of 468 amino acids, encompassing 29 epitopes. The CTL epitopes that passed the antigenicity, allergenicity, toxigenicity and immunogenicity assessment were four epitopes from S protein, one from M protein, two from N protein, 12 from the ORF1a polyprotein and none from E protein. While the HTL epitopes that passed the antigenicity, allergenicity, toxigenicity and INF-$$\gamma$$ γ were one from S protein, three from M protein, six from the ORF1a polyprotein and none from N and E proteins. All the vaccine properties and its ability to trigger the humoral and cell-mediated immune response were validated computationally. Molecular modeling, docking to TLR3, simulation, and molecular dynamics were also carried out. Finally, a molecular clone using pET28::mAID expression plasmid vector was prepared. Conclusion The overall results of the study suggest that the final multi-epitope chimeric construct is a potential candidate for an efficient protective vaccine against SARS-CoV-2.

Unveiling the Theoretical Mistakes in the World Bank Formation and its Implication on Survival of Africa Monetary Union

2019 ◽  
Vol 10 (1) ◽  
pp. 119-124
Author(s):  
Olatunji Abdul Shobande ◽  
Kingsley Chinonso Mark
Keyword(s):  
World Bank ◽  
Monetary Union ◽  
Political Interest ◽  
World Bank Group ◽  
Policy Makers ◽  
The World Bank ◽  
The World ◽  
Bank Group ◽  
The Stability ◽  
Developed Nations

Abstract The quest for urgent solution to resolve the world liquidity problem has continued to generate enthusiastic debates among political economists, policy makers and the academia. The argument has focused on whether the World Bank Group was established to enhance the stability of international financial system or meant to enrich the developed nations. This study argues that the existing political interest of the World Bank Group in Africa may serve as lesson learned to other ambitious African Monetary Union.

Design of potential IKK-β inhibitors using molecular docking and molecular dynamics techniques for their anti-cancer potential

2020 ◽  
Vol 16 ◽  
Author(s):  
Salam Pradeep Singh ◽  
Iftikar Hussain ◽  
Bolin Kumar Konwar ◽  
Ramesh Chandra Deka ◽  
Chingakham Brajakishor Singh
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Md Simulation ◽  
Inflammatory Diseases ◽  
Binding Free Energy ◽  
Anti Cancer ◽  
Dietary Phytochemicals ◽  
Toxicity Analysis ◽  
The Stability ◽  
Stable Trajectory

Aim and Objective: To evaluate a set of seventy phytochemicals for their potential ability to bind the inhibitor of nuclear factor kappaB kinase beta (IKK-β) which is a prime target for cancer and inflammatory diseases. Materials and Methods: Seventy phytochemicals were screened against IKK-β enzyme using DFT-based molecular docking technique and the top docking hits were carried forward for molecular dynamics (MD) simulation protocols. The adme-toxicity analysis was also carried out for the top docking hits. Results: Sesamin, matairesinol and resveratrol were found to be the top docking hits with a total score of -413 kJ/mol, -398.11 kJ/mol and 266.73 kJ/mol respectively. Glu100 and Gly102 were found to be the most common interacting residues. The result from MD simulation observed a stable trajectory with a binding free energy of -107.62 kJ/mol for matairesinol, -120.37 kJ/mol for sesamin and -40.56 kJ/mol for resveratrol. The DFT calculation revealed the stability of the compounds. The ADME-Toxicity prediction observed that these compounds fall within the permissible area of Boiled-Egg and it does not violate any rule for pharmacological criteria, drug-likeness etc. Conclusion: The study interprets that dietary phytochemicals are potent inhibitors of IKK-β enzyme with favourable binding affinity and less toxic effects. In fact, there is a gradual rise in the use of plant-derived molecules because of its lesser side effects compared to chemotherapy. The study has also provided an insight by which the phytochemicals inhibited the IKK-β enzyme. The investigation would also provide in understanding the inhibitory mode of certain dietary phytochemicals in treating cancer.

scholarly journals Nanocarriers, Progenitor Cells, Combinational Approaches, and New Insights on the Retinal Therapy

2021 ◽  
Vol 22 (4) ◽  
pp. 1776
Author(s):  
Elham Pishavar ◽  
Hongrong Luo ◽  
Johanna Bolander ◽  
Antony Atala ◽  
Seeram Ramakrishna
Keyword(s):  
Drug Delivery ◽  
Progenitor Cells ◽  
Transfection Efficiency ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Therapeutic Approaches ◽  
Age Related ◽  
Nanofibrous Scaffolds ◽  
The Stability

Progenitor cells derived from the retinal pigment epithelium (RPECs) have shown promise as therapeutic approaches to degenerative retinal disorders including diabetic retinopathy, age-related macular degeneration and Stargardt disease. However, the degeneration of Bruch’s membrane (BM), the natural substrate for the RPE, has been identified as one of the major limitations for utilizing RPECs. This degeneration leads to decreased support, survival and integration of the transplanted RPECs. It has been proposed that the generation of organized structures of nanofibers, in an attempt to mimic the natural retinal extracellular matrix (ECM) and its unique characteristics, could be utilized to overcome these limitations. Furthermore, nanoparticles could be incorporated to provide a platform for improved drug delivery and sustained release of molecules over several months to years. In addition, the incorporation of tissue-specific genes and stem cells into the nanostructures increased the stability and enhanced transfection efficiency of gene/drug to the posterior segment of the eye. This review discusses available drug delivery systems and combination therapies together with challenges associated with each approach. As the last step, we discuss the application of nanofibrous scaffolds for the implantation of RPE progenitor cells with the aim to enhance cell adhesion and support a functionally polarized RPE monolayer.

scholarly journals Endothelial activation and dysfunction in COVID-19: from basic mechanisms to potential therapeutic approaches

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Yuefei Jin ◽  
Wangquan Ji ◽  
Haiyan Yang ◽  
Shuaiyin Chen ◽  
Weiguo Zhang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Endothelial Activation ◽  
World Health ◽  
Therapeutic Approaches ◽  
Inflammatory Reactions ◽  
Angiotensin Converting Enzyme 2 ◽  
Therapeutic Implications ◽  
Endothelial Inflammation ◽  
The World ◽  
Health Organization

AbstractOn 12 March 2020, the outbreak of coronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organization. As of 4 August 2020, more than 18 million confirmed infections had been reported globally. Most patients have mild symptoms, but some patients develop respiratory failure which is the leading cause of death among COVID-19 patients. Endothelial cells with high levels of angiotensin-converting enzyme 2 expression are major participants and regulators of inflammatory reactions and coagulation. Accumulating evidence suggests that endothelial activation and dysfunction participate in COVID-19 pathogenesis by altering the integrity of vessel barrier, promoting pro-coagulative state, inducing endothelial inflammation, and even mediating leukocyte infiltration. This review describes the proposed cellular and molecular mechanisms of endothelial activation and dysfunction during COVID-19 emphasizing the principal mediators and therapeutic implications.

scholarly journals Histamine Intolerance—The More We Know the Less We Know. A Review

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2228
Author(s):  
Martin Hrubisko ◽  
Radoslav Danis ◽  
Martin Huorka ◽  
Martin Wawruch
Keyword(s):  
Gold Standard ◽  
Multidisciplinary Approach ◽  
Adverse Reactions ◽  
Immunological Response ◽  
Food Intolerance ◽  
Therapeutic Approaches ◽  
Complex Time ◽  
Histamine Intolerance ◽  
The World ◽  
H1 Antihistamines

The intake of food may be an initiator of adverse reactions. Food intolerance is an abnormal non-immunological response of the organism to the ingestion of food or its components in a dosage normally tolerated. Despite the fact that food intolerance is spread throughout the world, its diagnosing is still difficult. Histamine intolerance (HIT) is the term for that type of food intolerance which includes a set of undesirable reactions as a result of accumulated or ingested histamine. Manifestations may be caused by various pathophysiological mechanisms or a combination of them. The problem with a “diagnosis” of HIT is precisely the inconstancy and variety of the manifestations in the same individual following similar stimuli. The diagnosing of HIT therefore requires a complex time-demanding multidisciplinary approach, including the systematic elimination of disorders with a similar manifestation of symptoms. Among therapeutic approaches, the gold standard is a low-histamine diet. A good response to such a diet is considered to be confirmation of HIT. Alongside the dietary measures, DAO supplementation supporting the degradation of ingested histamine may be considered as subsidiary treatment for individuals with intestinal DAO deficiency. If antihistamines are indicated, the treatment should be conscious and time-limited, while 2nd or 3rd generation of H1 antihistamines should take precedence.

scholarly journals Treatment of Rheumatoid Arthritis with Traditional Chinese Medicine

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Wen-Yuan Lee ◽  
Hsin-Yi Chen ◽  
Kuan-Chung Chen ◽  
Calvin Yu-Chian Chen
Keyword(s):  
Rheumatoid Arthritis ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Protein Complex ◽  
Chronic Inflammatory Disease ◽  
Dynamics Simulation ◽  
Current Therapy ◽  
Potential Candidate ◽  
Interleukin 6 Receptor ◽  
The Stability

Rheumatoid arthritis (RA) is a chronic inflammatory disease that will affect quality of life and, working efficiency, and produce negative thoughts for patients. Current therapy of RA is treated with disease-modifying antirheumatic drugs (DMARDs). Although most of these treatment methods are effective, most patients still have a pleasant experience either due to poor efficacy or side effects or both. Interleukin-6 receptor (IL6R) is important in the pathogenesis of RA. In this study, we would like to detect the potential candidates which inhibit IL6R against RA from traditional Chinese medicine (TCM). We use TCM compounds from the TCM Database@Taiwan for virtually screening the potential IL6R inhibitors. The TCM candidate compound, calycosin, has potent binding affinity with IL6R protein. The molecular dynamics simulation was employed to validate the stability of interaction in the protein complex with calycosin. The analysis indicates that protein complex with calycosin is more stable. In addition, calycosin is known to be one of the components ofAngelica sinensis, which has been indicated to have an important role in the treatment of rheumatoid arthritis. Therefore, calycosin is a potential candidate as lead compounds for further study in drug development process with IL6R protein against rheumatoid arthritis.

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