scholarly journals In Silico Studies on Psilocybin Drug Derivatives Against SARS-CoV-2 and Cytokine Storm of Human Interleukin-6 Receptor

2022 ◽  
Vol 12 ◽  
Author(s):  
Faez Iqbal Khan ◽  
Fakhrul Hassan ◽  
Dakun Lai
Keyword(s):  
Free Energy ◽  
Structural Dynamics ◽  
Interleukin 6 ◽  
In Silico ◽  
Chemotherapeutic Agents ◽  
Cytokine Storm ◽  
Anticancer Properties ◽  
In Silico Studies ◽  
Interleukin 6 Receptor ◽  
Different Sources

Various metabolites identified with therapeutic mushrooms have been found from different sources and are known to have antibacterial, antiviral, and anticancer properties. Over thousands soil growth-based mushroom metabolites have been discovered, and utilized worldwide to combat malignancy. In this study, psilocybin-mushroom that contains the psychedelic compounds such as psilacetin, psilocin, and psilocybine were screened and found to be inhibitors of SARS-CoV-2 Mprotease. It has been found that psilacetin, psilocin, and psilocybine bind to Mprotease with −6.0, −5.4, and −5.8 kcal/mol, respectively. Additionally, the psilacetin was found to inhibit human interleukin-6 receptors to reduce cytokine storm. The binding of psilacetin to Mprotease of SARS-CoV-2 and human interleukin-6 receptors changes the structural dynamics and Gibbs free energy patterns of proteins. These results suggested that psilocybin-mushroom could be utilized as viable potential chemotherapeutic agents for SARS-CoV-2.

scholarly journals Peptides with Dual Antimicrobial–Anticancer Activity: Strategies to Overcome Peptide Limitations and Rational Design of Anticancer Peptides

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4245
Author(s):  
Yamil Liscano ◽  
Jose Oñate-Garzón ◽  
Jean Paul Delgado
Keyword(s):  
Anticancer Activity ◽  
In Silico ◽  
Rational Design ◽  
A Priori ◽  
Current Status ◽  
Anticancer Properties ◽  
Anticancer Peptides ◽  
In Silico Studies ◽  
Wide Range ◽  
Improved Stability

Peptides are naturally produced by all organisms and exhibit a wide range of physiological, immunomodulatory, and wound healing functions. Furthermore, they can provide with protection against microorganisms and tumor cells. Their multifaceted performance, high selectivity, and reduced toxicity have positioned them as effective therapeutic agents, representing a positive economic impact for pharmaceutical companies. Currently, efforts have been made to invest in the development of new peptides with antimicrobial and anticancer properties, but the poor stability of these molecules in physiological environments has triggered a bottleneck. Therefore, some tools, such as nanotechnology and in silico approaches can be applied as alternatives to try to overcome these obstacles. In silico studies provide a priori knowledge that can lead to the development of new anticancer peptides with enhanced biological activity and improved stability. This review focuses on the current status of research in peptides with dual antimicrobial–anticancer activity, including advances in computational biology using in silico analyses as a powerful tool for the study and rational design of these types of peptides.

scholarly journals In vitro selection of an RNA aptamer yields an interleukin-6/interleukin-6 receptor interaction inhibitor

2021 ◽  
Author(s):  
Takehiro Ando ◽  
Mizuki Yamamoto ◽  
Yukio Takamori ◽  
Keita Tsukamoto ◽  
Daisuke Fuji ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
In Vitro Selection ◽  
Receptor Interaction ◽  
Rna Aptamer ◽  
Cytokine Storm ◽  
Interleukin 6 Receptor ◽  
Systematic Evolution ◽  
Exponential Enrichment ◽  
Selection Of

ABSTRACT Interleukin-6 (IL-6) binds to IL-6 receptor (IL-6R) subunit, related to autoimmune diseases and cytokine storm in COVID-19. In this study we performed Systematic Evolution of Ligands by Exponential enrichment (SELEX) and identified a novel RNA aptamer. This RNA aptamer not only bound to IL-6R with a dissociation constant of 200 nM, but also inhibited the interaction of IL-6R with IL-6.

scholarly journals Cytokine Storm, Corticosteroids and İnterleukin-6 Receptor Antibodies in Context of Antiinflammatory Treatment in COVID-19

2020 ◽  
pp. 67-75
Author(s):  
Ozgur Karcioglu ◽  
Goksu Afacan ◽  
Bilgen Ozkaya ◽  
Ebru Yilmaz ◽  
Eylem Ersan ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
Viral Infections ◽  
Signs And Symptoms ◽  
Clinical Findings ◽  
Rapid Progression ◽  
Cytokine Storm ◽  
Inflammatory Status ◽  
Interleukin 6 Receptor ◽  
Short Time ◽  
Receptor Antibodies

It is well established that cytokine storm is associated with more severe clinical course of COVID-19. Many clinical findings of COVID-19 and other severe viral infections (e.g. fever, muscle pain, respiratory distress, cough), are directly attributed to cytokine storm. For example, IL-6 and IL-10 can be used as predictors for expedient diagnosis of patients with higher risk of deterioration. Hyper-inflammatory status in patients with severe COVID-19 is to be mitigated to alleviate signs and symptoms in cytokine storm. In case of deterioration of oxygenation and rapid progression of imaging (CT) findings, glucocorticoids can be used for a short time (3-5 days) for patients in whom overactivation of the body's inflammatory response is suspected. On the other hand, interleukin-6 receptor antibodies tocilizumab, sarilumab, siltuximab can be used as immunomodulators, to suppress inflammation and to alleviate fever and other manifestations of immune response. Their beneficial efficacy is especially remarkable during the cytokine storm period. It should be kept in mind that the agents to be used in the management of any given patient should be tailored for each situation.

scholarly journals An In Silico Study of a Novel rpoB Insertion in a Cluster of Clinical Strains of Mycobacterium tuberculosis Highly-Rifampicin Resistant

2017 ◽  
Author(s):  
Maria Lucia R. Rossetti ◽  
Pedro Almeida da Silva ◽  
Raquel Maschmann ◽  
Andrea von Groll ◽  
Leonardo S. Esteves ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Virtual Screening ◽  
Rna Polymerase ◽  
In Silico ◽  
Chemotherapeutic Agents ◽  
Single Amino Acid ◽  
Mutant Form ◽  
Clinical Strains ◽  
In Silico Studies ◽  
Biological Cost

Rifampicin is one of the most important chemotherapeutic agents used in the treatment of tuberculosis. M. tuberculosis clinical strains resistant to rifampicin harbor mainly mutation in an 81-base pair region of rpoB. These mutations mainly consist of single amino acid substitutions. However insertions also can be related with rifampicin resistance strains. Herein, we described an insertion of 12 nucleotides in clinical isolates of M. tuberculosis resistant to rifampicin, all obtained from inmates. To evaluate the importance this insertion in surviving and drug resistance, it were carried out fitness experimental assays as well as in silico studies of 3D structural models, molecular docking simulations and virtual screening. The medical records of the seven patients showed all were previously treated to tuberculosis. Growth curves shown that the insertion determines a biological cost when compared to wild type rpoB and katG; or the double mutated rpoB S531L and katG S315T. From docking and molecular dynamics simulations it can be inferred that the insertion does not affect the process of synthesis of RNA transcripts. On the other hand, in the mutant RNAP-RIF complex rifampicin confirmed a low affinity interaction for the mutant form. Interesting, virtual screening for potential inhibitors for wtRNAP and mRNAP using a library of 1446 compounds approved by the FDA showed that the best ligands were mainly compounds with antibiotic activity, although the targets involved in the pharmacological action are other than RNAP. In conclusion, seven strains of M. tuberculosis RIF resistant that present an insertion of four amino acids in RNA polymerase showed by growth curve assays, a biological cost. Further, bioinformatics tools had characterized the putative drug resistance dynamic as well as the maintenance of RNA polymerase activity.

scholarly journals Use of tocilizumab in the combination treatment of a COVID-19 patient with concomitant rheumatoid arthritis (a case report)

2021 ◽  
Vol 23 (5) ◽  
pp. 739-748
Author(s):  
V. A. Vizir ◽  
A. S. Sadomov ◽  
O. V. Demidenko
Keyword(s):  
Rheumatoid Arthritis ◽  
Monoclonal Antibody ◽  
Combination Treatment ◽  
Interleukin 6 ◽  
Clinical Case ◽  
Clinical Laboratory ◽  
Cytokine Storm ◽  
X Ray ◽  
Interleukin 6 Receptor ◽  
Receptor Monoclonal Antibody

The aim is to familiarize practitioners with the clinical case of tocilizumab use in the combination treatment of the coronavirus disease (COVID-19) patient with concomitant rheumatoid arthritis. Materials and methods. The clinical case shows our own follow-up of COVID-19 clinical course in the patient with concomitant rheumatoid arthritis during combination treatment with the use of a recombinant humanized anti-interleukin-6 receptor monoclonal antibody tocilizumab. Results. The patient with a severe COVID-19 course, whose examination and treatment results are given in the article, was comorbid for rheumatoid arthritis. The cytokine storm development at the hospital stage was confirmed by an increase in markers of systemic inflammation: C-reactive protein, D-dimer, fibrinogen, an almost 50-fold increase in serum interleukin-6 level, as well as absolute and relative lymphocytopenia. Despite the anti-inflammatory therapy administered with systemic corticosteroids, the patient’s condition progressively worsened. After assessing the indications and contraindications, it was decided to use the interleukin-6 receptor inhibitor tocilizumab, followed by rapid clinical, laboratory and X-ray positive response to the treatment. The understanding of tocilizumab use in patients with COVID-19 at the current stage was formed based on the comparative analysis of our own clinical case data and the results of relevant clinical trials, world recommendations and guidelines. Conclusions. The use of recombinant humanized anti-interleukin-6 receptor monoclonal antibody tocilizumab in the combination treatment of severe COVID-19 with concomitant rheumatoid arthritis is pathogenetically based and decreases the main clinical and laboratory signs of cytokine storm, respiratory failure, improves chest x-ray findings and reduces the length of hospital stay. Further large randomized placebo-controlled trials including the population of patients with various comorbid conditions are needed to clarify conclusively the place and role of anti-cytokine drugs in the treatment of COVID-19 patients.

scholarly journals ZIKA VIRUS SERENE PROTEASE COMPLEX (NS2B-NS3) INHIBITION BY 2-AMINO-5-{[(1Z)-AMINO({[(Z)-BENZOYL]IMINO})METHYL]AMINO}-N-(5-AMINO-7-{[CARBAMOYL(PHENYL)METHYL]AMINO}-6-OXOHEPTYL)PENTANAMIDE, IN SILICO STUDIES

2017 ◽  
Vol 10 (5) ◽  
pp. 210
Author(s):  
Kalpana Virendra Singh ◽  
Ramchander Merugu ◽  
Jeeven Singh Solanki
Keyword(s):  
Free Energy ◽  
Serine Protease ◽  
Zika Virus ◽  
In Silico ◽  
Hydrophobic Interactions ◽  
Free Energy Calculations ◽  
Protease Inhibition ◽  
Docking Simulations ◽  
In Silico Studies ◽  
Ns3 Protease

Objective: The present in silico study is taken to report 2-amino-5-{[(1Z) -amino ({[(Z) -benzoyl] imino}) methyl] amino} -N-(5-amino-7-{[carbamoyl (phenyl) methyl] amino} -6-oxoheptyl) pentanamide as Zika virus (ZIKV) NS2B-NS3 protease inhibitor.Methods: In silico studies performed on online docking servers. NS2B-NS3 serine protease from ZIKV with PDB ID: 5GJ4 a hydrolase with total structure weight of 102878.54 is selected as the target. Docking server is used for carrying out docking calculations. Lamarckian genetic algorithm and the Solis and Wets local search methods are used for performing docking simulations. Free energy calculations, hydrogen bond (HB) formation, polar and hydrophobic interactions and HB plot are studied in this study.Results: Binding pocket is found on a serine protease NS2B chain A. Binding site predictions propose NKK as the suitable ligand for binding, which has structure closely related to the proposed ligand2-amino-5-{[(1Z) -amino ({[(Z) -benzoyl] imino}) methyl] amino} -N-(5-amino-7-{[carbamoyl (phenyl) methyl] amino} -6-oxoheptyl) pentanamide. Free energy of binding is - 4.08 kcal/Mol and inhibition constant (Ki) is very less 1.02 mm. The ligand binds to chain A of NS2B and chain B of NS3 serine protease. The legend is bound to serine protease complex through strong HB, formed between THR 60 (A) and N6 of ligand, GLU62 (A) and N8 of ligand, ARG 55 (A) and N3 of ligand and ASN108 (B) and N7 of ligand apart from polar and hydrophobic interactions.Conclusion: Docking studies performed establishes the proposed ligand2-amino-5-{[(1Z)-amino ({[(Z)-benzoyl] imino}) methyl] amino} -N-(5- amino-7-{[carbamoyl (phenyl) methyl] amino}-6-oxoheptyl) pentanamide as a molecule which can be used for the inhibition of ZIKV NS2B-NS3 serine protease.Keywords: Zika virus, NS2B-NS3 protease, Inhibition, In silico.

scholarly journals On the role of bacterial metalloproteases in COVID-19 associated cytokine storm

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
László Földvári-Nagy ◽  
Tamás Schnabel ◽  
Gabriella Dörnyei ◽  
Tamás Korcsmáros ◽  
Katalin Lenti
Keyword(s):  
Mortality Rate ◽  
Interleukin 6 ◽  
Viral Infections ◽  
Inflammatory Responses ◽  
Membrane Receptors ◽  
Critical Element ◽  
Cytokine Storm ◽  
Interleukin 6 Receptor ◽  
Membrane Bound ◽  
Prophylactic Use

AbstractThe cytokine release syndrome or cytokine storm, which is the hyper-induction of inflammatory responses has a central role in the mortality rate of COVID-19 and some other viral infections. Interleukin-6 (IL-6) is a key player in the development of cytokine storms. Shedding of interleukin-6 receptor (IL-6Rα) results in the accumulation of soluble interleukin-6 receptors (sIL-6R). Only relatively few cells express membrane-bound IL-6Rα. However, sIL-6R can act on potentially all cells and organs through the ubiquitously expressed gp130, the coreceptor of IL-6Rα. Through this, so-called trans-signaling, IL-6–sIL-6R is a powerful factor in the development of cytokine storms and multiorgan involvement. Some bacteria (e.g., Serratia marcescens, Staphylococcus aureus, Pseudomonas aeruginosa, Listeria monocytogenes), commonly considered to cause co-infections during viral pneumonia, can directly induce the shedding of membrane receptors, including IL-6Rα, or enhance endogenous shedding mechanisms causing the increase of sIL-6R level. Here we hypothesise that bacteria promoting shedding and increase the sIL-6R level can be an important contributing factor for the development of cytokine storms. Therefore, inhibition of IL-6Rα shedding by drastically reducing the number of relevant bacteria may be a critical element in reducing the chance of a cytokine storm. Validation of this hypothesis can support the consideration of the prophylactic use of antibiotics more widely and at an earlier stage of infection to decrease the mortality rate of COVID-19.

IN-SILICO STUDIES OF ANTI-PROLIFERATIVE CURCUMIN ANALOGS

2021 ◽  
pp. 24-26
Author(s):  
Monu Kumar Shukla
Keyword(s):  
In Silico ◽  
3D Qsar ◽  
Qsar Model ◽  
Physicochemical Characteristics ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Qsar Studies ◽  
Anticancer Properties ◽  
Curcumin Analogues ◽  
In Silico Studies

Prostate cancer affects males more than women. Curcumin, a bioactive component of turmeric, reported to have anticancer properties on several cancer cell lines. Researchers utilised molecular docking to generate new curcumin analogues, quantify their characteristics, and anticipate its mode of action. In this research article QSAR studies were performed on 40 curcumin analogues using V-life MDS 3.5 software. The physicochemical characteristics were computed using Molinspiration Cheminformatics software. The best QSAR model for 2D and 3D QSAR was selected. Then ten compounds were designed and improved based on model results directly linked to activity. The in-silico approach predicted the good biological activity of compounds. Docking studies were performed using Akt1 as a probable target. Among the developed compounds, MKS50 has the best docking score (-7.175 kcal/mol). This study will provide a new path for the design, synthesis, and biological evaluation of novel curcumin analogues.

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