scholarly journals SARS-CoV-2 transcriptome analysis and molecular cataloguing of immunodominant epitopes for multi-epitope based vaccine design

2020 ◽  
Author(s):  
Sandeep Kumar Kushwaha ◽  
Veerbhan Kesarwani ◽  
Samraggi Choudhury ◽  
Sonu Gandhi ◽  
Shailesh Sharma
Keyword(s):  
Molecular Docking ◽  
Immune Responses ◽  
B Cell ◽  
Cell Lines ◽  
Docking Studies ◽  
B Cell Receptors ◽  
B Cell Epitopes ◽  
Cell Receptors ◽  
Molecular Docking Studies ◽  
Mhc Molecules

AbstractSARS-CoV-2 is a single-stranded RNA virus that has caused more than 0.29 million deaths worldwide as of May 2020, and influence of COVID-19 pandemic is increasing continuously in the absence of approved vaccine and drug. Moreover, very limited information is available about SARS-CoV-2 expressed regions and immune responses. In this paper an effort has been made, to facilitate vaccine development by proposing multiple epitopes as potential vaccine candidates by utilising SARS-CoV-2 transcriptome data. Here, publicly available RNA-seq data of SARS-CoV-2 infection in NHBE and A549 human cell lines were used to construct SARS-CoV-2 transcriptome to understand disease pathogenesis and immune responses. In the first step, epitope prediction, MHC class I and II gene identification for epitopes, population coverage, antigenicity, immunogenicity, conservation and crossreactivity analysis with host antigens were performed by using SARS-CoV-2 transcriptome, and in the second step, structural compatibility of identified T-and B-cell epitopes were evaluated with MHC molecules and B-cell receptors through molecular docking studies. Quantification of MHC gene expression was also performed that indicated high variation in allele types and expression level of MHC genes with respect to cell lines. In A549 cell line, HLA-A*30:01:01:01 and HLA-B*44:03:01:01 were highly expressed, whereas 92 variants of HLA-A*24 genes such as HLA-A*24:02:01:01, HLA-A*24:286, HLA-A*24:479Q, HLA-A*24:02:134 and HLA-A*24:02:116 were highly expressed in NHBE cell lines. Prevalence of HLA-A*24 alleles was suggested as risk factors for H1N1 infection, and associated with type-1 diabetes. HLA-C*03:03, linked with male infertility factors was also highly expressed in SARS-CoV-2 infected NHBE cell lines. Finally, three potential T-cell and five B-cell epitopes were selected for molecular docking studies with twenty-two MHC molecules and two B-cell receptors respectively. The results of in silico analysis indicated that proposed epitopes have high potential to recognize immune response of SARS-CoV-2 infection. This study will facilitate in vitro and in vivo vaccine related research studies.

scholarly journals Synthesis, cytotoxicity evaluation and molecular docking studies on 2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone derivatives

RSC Advances ◽  
2021 ◽  
Vol 11 (50) ◽  
pp. 31433-31447
Author(s):  
Nopawit Khamto ◽  
Lada Chaichuang ◽  
Puracheth Rithchumpon ◽  
Worrapong Phupong ◽  
Phuangthip Bhoopong ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Docking Studies ◽  
Molecular Docking Studies ◽  
Biological Potency

Semi-synthetic DMC derivatives were synthesised and displayed biological potency against various cancer cell lines.

New furochromone derivatives as promising in‐vitro anti‐proliferative agents toward HepG ‐2 and MCF ‐7 cell lines with molecular docking studies

2020 ◽  
Vol 57 (7) ◽  
pp. 2748-2761
Author(s):  
Nagwa M. Fawzy ◽  
Khadiga M. Ahmed ◽  
Heba M. Abo‐Salem ◽  
Magdy S. Aly
Keyword(s):  
Molecular Docking ◽  
Cell Lines ◽  
Docking Studies ◽  
Molecular Docking Studies ◽  
Mcf 7

Novel Pyrazolyl Benzoxazole Conjugates: Design, Synthesis, Molecular Docking Studies and in vitro Anticancer Activities

2019 ◽  
Vol 16 (8) ◽  
pp. 619-626
Author(s):  
Arunkumar Thiriveedhi ◽  
Ratnakaram Venkata Nadh ◽  
Navuluri Srinivasu ◽  
Narayana Murthy Ganta
Keyword(s):  
Molecular Docking ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Docking Studies ◽  
Anticancer Activities ◽  
Molecular Docking Studies ◽  
Hybrid Molecules ◽  
Mcf 7

Nowadays, hybrid drugs have gained a significant role in the treatment of different health problems. Most of the hybrid molecules with different heterocyclic moieties were proved to be potent anti-tumor agents in cancer chemotherapy. Hence, the present study is aimed at the evaluation of in vitro anticancer activity of novel hybrid molecules (pyrazolyl benzoxazole conjugates) and to investigate their anticancer activity by molecular docking studies. Designed, synthesized and characterized the novel pyrazolyl benzoxazole conjugates. Anticancer activity of these compounds was determined by SRB assay. Then molecular docking studies were carried out against proto-oncogene tyrosine-protein kinase (ATP-Src, PDB: 2BDF), a putative target for cancer. All the synthesized compound derivatives were evaluated against MCF-7, KB, Hop62 and A549 cancer cell lines. Compounds 9b and 9c exhibited excellent anticancer activities with GI50 values of <0.1 µM against MCF-7 and A549 cell lines. Compound 9e exhibited good antitumor activity on MCF-7 and A-549 with GI50 values of 0.12 µM and 0.19 µM respectively. Compound 9g showed better anticancer activity on A-549 cancer cell line with GI50 of 0.34 µM. The two-hybrid molecules 9b and 9c are found to be comparably potent with the standard drug doxorubicin and may act as drug lead compounds in medicinal chemistry aspect. The present docking investigation proved that having benzoxazole of compound 9c at the position of benzofuran of reference compound (N-acetyl pyrazoline derivative) might be valid for contributing to anti-cancer activity.

Design, Synthesis, Anticancer Activity and Molecular Docking Studies of 2,5-Disubstituted-1,3,4-Oxadiazoles Containing Benzimidazole Moiety

2020 ◽  
Vol 17 (12) ◽  
pp. 959-968
Author(s):  
Ramamurthy Katikireddy ◽  
Ramu Kakkerla ◽  
M.P.S. Murali Krishna ◽  
Gandamalla Durgaiah ◽  
Y.N. Reddy
Keyword(s):  
Molecular Docking ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Hek293 Cell ◽  
Docking Studies ◽  
Design Synthesis ◽  
Molecular Docking Studies ◽  
Pin1 Protein

A series of benzimidazolyl-1,3,4-oxadiazoles (7a-k) were synthesized and evaluated for in vitro anticancer activity against HeLa, MCF7, A549, and HEK293 cell lines. The results indicate that compounds 7b, 7j and 7k have shown excellent anticancer activity and while most of the compounds were non toxic to normal HEK293 cell lines. Molecular docking results of the synthesized compounds with the target Pin1 protein were also discussed.

scholarly journals Anticancer and Molecular Docking Studies of 1-(5-substituted phenyl) isoxazol-3-yl)-5-phenyl-1H-tetrazoles

2019 ◽  
pp. 1-12
Author(s):  
N. Kaushik ◽  
N. Kumar ◽  
A. Kumar ◽  
S. Kumar ◽  
B. K. Chaudhary
Keyword(s):  
Molecular Docking ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Leukemia Cell ◽  
Docking Studies ◽  
High Dose ◽  
Molecular Docking Studies ◽  
Leukemia Cell Lines ◽  
Drug Discovery Program

Cancer a leading cause of human mortality worldwide is characterised by the unseemly growth of cellular mass and signalled through the enlargement of stress.  Management of cancer treatment is still buried and has been recently alerting the need to discover a drug molecule with lesser side effects. The objective of the present study is to explore the anticancer activity and docking studies of 1-(5-substituted phenyl) isoxazol-3-yl)-5-phenyl-1H-tetrazole derivatives. The compounds were evaluated for in-vitro anticancer activity under the drug discovery program of National Cancer Institute (NCI), USA. Only seven compounds were selected and screened for anticancer activity at a single high dose (10-5 M) using NCI 60 cancer cell lines. Among all the selected compounds, 4b and 4i exhibited significant anticancer activity against Leukemia cell lines. Molecular docking studies for the 5-phenyl-1-(5-substituted phenylisoxazol-3-yl)-1H-tetrazole analogues was done by Schrodinger software. Docking results stated that the compounds 4b and 4i has good dock score among the other derivatives which shows good binding efficiency towards receptor.

Furanone-functionalized benzothiazole derivatives: synthesis, in vitro cytotoxicity, ADME, and molecular docking studies

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Asif Husain ◽  
Silky Bedi ◽  
Shazia Parveen ◽  
Shah Alam Khan ◽  
Aftab Ahmad ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Human Cancer ◽  
Docking Studies ◽  
In Vitro Cytotoxicity ◽  
Standard Drug ◽  
Molecular Docking Studies ◽  
Benzothiazole Derivatives

Abstract In the present study, a novel series of new furanone-based benzothiazole derivatives (4a-j) were synthesized from 4-(benzo[d]thiazol-2-yl)-4-oxobutanoic acid (3) as potential anticancer agents. In vitro cytotoxicity against three human cancer cell lines (A549, MCF7, and DUI45) revealed substantial activity. Di-substituted compound, 4i emerged as a promising anticancer compound which showed IC50 values of 7.2 ± 0.5, 6.6 ± 1.4, and 7.3 ± 0.1 µM against A549, MCF7, and DUI45 cell lines, respectively. Four compounds 4c, 4e, 4f, and 4i evaluated for their acute toxicity were found to be non-toxic on the two vital organs (liver and heart). Further, these compounds were found to be more efficient and less hepatotoxic in comparison to standard drug doxorubicin. Molecular docking studies carried out with VEGFR-2 revealed compounds 4a and 4i as potential VEGFR-2 kinase inhibitors. In silico ADME evaluation was carried out to estimate and predict drug-likeness. Compound 4i demonstrated the best ADME parameters. Based on the results of docking analyses, ADME, and in vitro cytotoxicity, compound 4i is identified as the lead compound for further development of anticancer agents.

scholarly journals The Role of Aggregates of Therapeutic Protein Products in Immunogenicity: An Evaluation by Mathematical Modeling

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Liusong Yin ◽  
Xiaoying Chen ◽  
Abhinav Tiwari ◽  
Paolo Vicini ◽  
Timothy P. Hickling
Keyword(s):  
Mathematical Modeling ◽  
T Cell ◽  
Immune Responses ◽  
B Cell ◽  
Drug Efficacy ◽  
Therapeutic Protein ◽  
Mitigation Strategies ◽  
B Cell Receptors ◽  
Cell Receptors

Therapeutic protein products (TPP) have been widely used to treat a variety of human diseases, including cancer, hemophilia, and autoimmune diseases. However, TPP can induce unwanted immune responses that can impact both drug efficacy and patient safety. The presence of aggregates is of particular concern as they have been implicated in inducing both T cell-independent and T cell-dependent immune responses. We used mathematical modeling to evaluate several mechanisms through which aggregates of TPP could contribute to the development of immunogenicity. Modeling interactions between aggregates and B cell receptors demonstrated that aggregates are unlikely to induce T cell-independent immune responses by cross-linking B cell receptors because the amount of signal transducing complex that can form under physiologically relevant conditions is limited. We systematically evaluate the role of aggregates in inducing T cell-dependent immune responses using a recently developed multiscale mechanistic mathematical model. Our analysis indicates that aggregates could contribute to T cell-dependent immune response by inducing high affinity epitopes which may not be present in the nonaggregated TPP and/or by enhancing danger signals to break tolerance. In summary, our computational analysis is suggestive of novel insights into the mechanisms underlying aggregate-induced immunogenicity, which could be used to develop mitigation strategies.

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