scholarly journals In Silico Designing of a Multi-Epitope Based Vaccine Candidate Against Human Adenovirus Type B3 Respiratory Infections by Utilising Various Immunoinformatics Approaches

2021 ◽  
Vol 29 (1) ◽  
Author(s):  
Somnath Panda ◽  
Urmila Banik ◽  
Arun Kumar Adhikary
Keyword(s):  
Molecular Docking ◽  
Physicochemical Properties ◽  
In Silico ◽  
Vaccine Development ◽  
Vaccine Candidate ◽  
Respiratory Infections ◽  
Human Adenovirus ◽  
Adenovirus Type ◽  
Conventional Vaccine

Human adenovirus type B3 (HAdV-B3) causes severe respiratory infections, hence an efficient vaccine is required. Unfortunately, the presence of numerous hexon variations makes conventional vaccine designing difficult which warrants an alternative method. Therefore, an in silico multi-epitope vaccine had been constructed against appropriate hexon variants of HAdV-B3. The allergenicity, antigenicity, structure, physicochemical properties along with molecular docking with TLR-3 and TLR-9 had also been predicted. The constructed vaccine had 23 different epitopes. It showed non-allergic but antigenic nature with 30hours of half-life in vitro and exhibited thermostable nature. We anticipate that this will considerably reduce the time and expense of biological work needed for future vaccine development.

The Antiviral and Antimalarial Drug Repurposing in Quest of Chemotherapeutics to Combat COVID-19 Utilizing Structure-Based Molecular Docking

2020 ◽  
Vol 23 ◽  
Author(s):  
Sisir Nandi ◽  
Mohit Kumar ◽  
Mridula Saxena ◽  
Anil Kumar Saxena
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Drug Repurposing ◽  
Clinical Settings ◽  
The Novel ◽  
In Silico Docking ◽  
Biochemical Mechanisms ◽  
Novel Coronavirus ◽  
In Silico Molecular Docking

Background: The novel coronavirus disease (COVID-19) is caused by a new strain (SARS-CoV-2) erupted in 2019. Nowadays, it is a great threat that claims uncountable lives worldwide. There is no specific chemotherapeutics developed yet to combat COVID-19. Therefore, scientists have been devoted in the quest of the medicine that can cure COVID- 19. Objective: Existing antivirals such as ASC09/ritonavir, lopinavir/ritonavir with or without umifenovir in combination with antimalarial chloroquine or hydroxychloroquine have been repurposed to fight the current coronavirus epidemic. But exact biochemical mechanisms of these drugs towards COVID-19 have not been discovered to date. Method: In-silico molecular docking can predict the mode of binding to sort out the existing chemotherapeutics having a potential affinity towards inhibition of the COVID-19 target. An attempt has been made in the present work to carry out docking analyses of 34 drugs including antivirals and antimalarials to explain explicitly the mode of interactions of these ligands towards the COVID-19protease target. Results: 13 compounds having good binding affinity have been predicted towards protease binding inhibition of COVID-19. Conclusion: Our in silico docking results have been confirmed by current reports from clinical settings through the citation of suitable experimental in vitro data available in the published literature.

In Silico Appraisal, Synthesis, Antibacterial Screening and DNA Cleavage for 1,2,5-thiadiazole Derivative

2019 ◽  
Vol 15 (5) ◽  
pp. 445-455 ◽  
Author(s):  
Suraj N. Mali ◽  
Sudhir Sawant ◽  
Hemchandra K. Chaudhari ◽  
Mustapha C. Mandewale
Keyword(s):  
Molecular Docking ◽  
Dna Cleavage ◽  
In Silico ◽  
Oral Absorption ◽  
Inhibition Mechanism ◽  
Hydrogen Binding ◽  
Docking Score ◽  
Antibacterial Screening ◽  
Mycobacteria Tuberculosis

Background: : Thiadiazole not only acts as “hydrogen binding domain” and “two-electron donor system” but also as constrained pharmacophore. Methods:: The maleate salt of 2-((2-hydroxy-3-((4-morpholino-1, 2,5-thiadiazol-3-yl) oxy) propyl) amino)- 2-methylpropan-1-ol (TML-Hydroxy)(4) has been synthesized. This methodology involves preparation of 4-morpholino-1, 2,5-thiadiazol-3-ol by hydroxylation of 4-(4-chloro-1, 2,5-thiadiazol-3-yl) morpholine followed by condensation with 2-(chloromethyl) oxirane to afford 4-(4-(oxiran-2-ylmethoxy)-1,2,5-thiadiazol- 3-yl) morpholine. Oxirane ring of this compound was opened by treating with 2-amino-2-methyl propan-1- ol to afford the target compound TML-Hydroxy. Structures of the synthesized compounds have been elucidated by NMR, MASS, FTIR spectroscopy. Results: : The DSC study clearly showed that the compound 4-maleate salt is crystalline in nature. In vitro antibacterial inhibition and little potential for DNA cleavage of the compound 4 were explored. We extended our study to explore the inhibition mechanism by conducting molecular docking, ADMET and molecular dynamics analysis by using Schrödinger. The molecular docking for compound 4 showed better interactions with target 3IVX with docking score of -8.508 kcal/mol with respect to standard ciprofloxacin (docking score= -3.879 kcal/mol). TML-Hydroxy was obtained in silico as non-carcinogenic and non-AMES toxic with good percent human oral absorption profile (69.639%). TML-Hydroxy showed the moderate inhibition against Mycobacteria tuberculosis with MIC 25.00 μg/mL as well as moderate inhibition against S. aureus, Bacillus sps, K. Pneumoniae and E. coli species. Conclusion: : In view of the importance of the 1,2,5-thiadiazole moiety involved, this study would pave the way for future development of more effective analogs for applications in medicinal field.

Virtual Screening, Molecular docking and in-silico ADME-Tox analysis for identification of potential main protease (Mpro) enzyme inhibitors

2020 ◽  
Vol 18 ◽  
Author(s):  
Debadash Panigrahi ◽  
Ganesh Prasad Mishra
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
In Silico ◽  
Data Bank ◽  
Future Research ◽  
Reference Compound ◽  
Unexpected Death ◽  
Main Protease ◽  
In Silico Admet

Objective:: Recent pandemic caused by SARS-CoV-2 described in Wuhan China in December-2019 spread widely almost all the countries of the world. Corona virus (COVID-19) is causing the unexpected death of many peoples and severe economic loss in several countries. Virtual screening based on molecular docking, drug-likeness prediction, and in silico ADMET study has become an effective tool for the identification of small molecules as novel antiviral drugs to treat diseases. Methods:: In the current study, virtual screening was performed through molecular docking for identifying potent inhibitors against Mpro enzyme from the ZINC library for the possible treatment of COVID-19 pandemic. Interestingly, some compounds are identified as possible anti-covid-19 agents for future research. 350 compounds were screened based on their similarity score with reference compound X77 from ZINC data bank and were subjected to docking with crystal structure available of Mpro enzyme. These compounds were then filtered by their in silico ADME-Tox and drug-likeness prediction values. Result:: Out of these 350 screened compounds, 10 compounds were selected based on their docking score and best docked pose in comparison to the reference compound X77. In silico ADME-Tox and drug likeliness predictions of the top compounds were performed and found to be excellent results. All the 10 screened compounds showed significant binding pose with the target enzyme main protease (Mpro) enzyme and satisfactory pharmacokinetic and toxicological properties. Conclusion:: Based on results we can suggest that the identified compounds may be considered for therapeutic development against the COVID-19 virus and can be further evaluated for in vitro activity, preclinical, clinical studies and formulated in a suitable dosage form to maximize their bioavailability.

scholarly journals In silico molecular docking and in vitro antimicrobial efficacy of phytochemicals against multi-drug-resistant enteroaggregative Escherichia coli and non-typhoidal Salmonella spp.

Gut Pathogens ◽  
2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Padikkamannil Abishad ◽  
Pollumahanti Niveditha ◽  
Varsha Unni ◽  
Jess Vergis ◽  
Nitin Vasantrao Kurkure ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Molecular Docking ◽  
In Silico ◽  
Docking Studies ◽  
Antimicrobial Efficacy ◽  
Drug Resistant ◽  
Protein Motifs ◽  
Phytochemical Compounds ◽  
In Silico Molecular Docking

Abstract Background In the wake of emergence of antimicrobial resistance, bioactive phytochemical compounds are proving to be important therapeutic agents. The present study envisaged in silico molecular docking as well as in vitro antimicrobial efficacy screening of identified phytochemical ligands to the dispersin (aap) and outer membrane osmoporin (OmpC) domains of enteroaggregative Escherichia coli (EAEC) and non-typhoidal Salmonella spp. (NTS), respectively. Materials and methods The evaluation of drug-likeness, molecular properties, and bioactivity of the identified phytocompounds (thymol, carvacrol, and cinnamaldehyde) was carried out using Swiss ADME, while Protox-II and StopTox servers were used to identify its toxicity. The in silico molecular docking of the phytochemical ligands with the protein motifs of dispersin (PDB ID: 2jvu) and outer membrane osmoporin (PDB ID: 3uu2) were carried out using AutoDock v.4.20. Further, the antimicrobial efficacy of these compounds against multi-drug resistant EAEC and NTS strains was determined by estimating the minimum inhibitory concentrations and minimum bactericidal concentrations. Subsequently, these phytochemicals were subjected to their safety (sheep and human erythrocytic haemolysis) as well as stability (cationic salts, and pH) assays. Results All the three identified phytochemicals ligands were found to be zero violators of Lipinski’s rule of five and exhibited drug-likeness. The compounds tested were categorized as toxicity class-4 by Protox-II and were found to be non- cardiotoxic by StopTox. The docking studies employing 3D model of dispersin and ompC motifs with the identified phytochemical ligands exhibited good binding affinity. The identified phytochemical compounds were observed to be comparatively stable at different conditions (cationic salts, and pH); however, a concentration-dependent increase in the haemolytic assay was observed against sheep as well as human erythrocytes. Conclusions In silico molecular docking studies provided useful insights to understand the interaction of phytochemical ligands with protein motifs of pathogen and should be used routinely before the wet screening of any phytochemicals for their antibacterial, stability, and safety aspects.

scholarly journals In Vitro and In Vivo Evaluation of Human Adenovirus Type 49 as a Vector for Therapeutic Applications

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1483
Author(s):  
Emily A. Bates ◽  
John R. Counsell ◽  
Sophie Alizert ◽  
Alexander T. Baker ◽  
Natalie Suff ◽  
...  
Keyword(s):  
Viral Vector ◽  
Ex Vivo ◽  
Human Adenovirus ◽  
Adenovirus Type ◽  
Cell Types ◽  
In Vivo Evaluation ◽  
In Vivo Biodistribution ◽  
Adenovirus Type 5

The human adenovirus phylogenetic tree is split across seven species (A–G). Species D adenoviruses offer potential advantages for gene therapy applications, with low rates of pre-existing immunity detected across screened populations. However, many aspects of the basic virology of species D—such as their cellular tropism, receptor usage, and in vivo biodistribution profile—remain unknown. Here, we have characterized human adenovirus type 49 (HAdV-D49)—a relatively understudied species D member. We report that HAdV-D49 does not appear to use a single pathway to gain cell entry, but appears able to interact with various surface molecules for entry. As such, HAdV-D49 can transduce a broad range of cell types in vitro, with variable engagement of blood coagulation FX. Interestingly, when comparing in vivo biodistribution to adenovirus type 5, HAdV-D49 vectors show reduced liver targeting, whilst maintaining transduction of lung and spleen. Overall, this presents HAdV-D49 as a robust viral vector platform for ex vivo manipulation of human cells, and for in vivo applications where the therapeutic goal is to target the lung or gain access to immune cells in the spleen, whilst avoiding liver interactions, such as intravascular vaccine applications.

Construction and characterization of a replication-competent human adenovirus type 3-based vector as a live-vaccine candidate and a viral delivery vector

Vaccine ◽  
2009 ◽  
Vol 27 (8) ◽  
pp. 1145-1153 ◽  
Author(s):  
Qiwei Zhang ◽  
Xiaobo Su ◽  
Donald Seto ◽  
Bo-jian Zheng ◽  
Xingui Tian ◽  
...  
Keyword(s):  
Vaccine Candidate ◽  
Human Adenovirus ◽  
Adenovirus Type ◽  
Live Vaccine ◽  
Delivery Vector ◽  
Type 3

scholarly journals Computational Analysis for Physicochemical Properties of Compounds in Senna auriculata Leaves Methanolic Extract to have Antidiabetic Potentials and their Molecular Interaction with α-amylase

2021 ◽  
pp. 30-42
Author(s):  
Abdulaziz Bin Dukhyil
Keyword(s):  
Molecular Docking ◽  
Physicochemical Properties ◽  
Methanolic Extract ◽  
Natural Compounds ◽  
Physicochemical Analysis ◽  
Dynamics Simulation ◽  
Carbohydrate Hydrolysis ◽  
Catalytic Active Site ◽  
Inhibitory Potential

Aims: Diabetes mellitus (DM) is chronic disorder well known for increased glucose level in blood. This disease can be controlled by inhibiting the enzyme (e.g., α-amylase) involve in carbohydrate hydrolysis. Senna auriculata leaves methanolic extract (SALME) have potential antidiabetic properties and it was also found to be safe in preclinical studies. In this study the aim was to explore the molecular interactions of α-amylase and bioactive compounds in SALME and their physicochemical properties. Methodology: Computational approach such as molecular docking and physicochemical analysis prediction was applied to understand the antidiabetic potential of natural compounds present in SALME. Results: The results showed from physicochemical analysis that out of 11 only 7 compounds are having drug like properties which are orally and intestinally better bioavailable. Furthermore, molecular docking analysis explained that three compounds (C3, C4, and C7) have lower binding energy, ΔG (-8, -9.1, -9.5 kcal/mol) and better binding affinity, Ki (7.31 x 105, 4.68 x 106, and 9.2 x 106 M-1, respectively) than the acarbose ΔG (-7.8 kcal/mol) and Ki (6.18 x 105 M-1), a well-known FDA approved medication for DM. The study also explained the binding pattern that the catalytic residue such as Asp197, Glu233 and Asp300 are involved in stabilizing the natural compounds with in the catalytic active site of target enzyme. Conclusions: From the results it has been concluded that these three compounds found in SALME have better inhibitory potential for α-amylase in comparison with acarbose. Further validation of the findings is required through molecular dynamics simulation, ADME-T study, and in-vitro enzyme inhibition by the purified compounds.

scholarly journals Anti-Adenovirus Activity of the Medical Intranasal Drug Nazoferon

2021 ◽  
Vol 83 (2) ◽  
pp. 73-81
Author(s):  
O.Yu. Povnitsa ◽  
◽  
L.O. Biliavska ◽  
Yu.B. Pankivska ◽  
S.D. Zagorodnya ◽  
...  
Keyword(s):  
Respiratory Infections ◽  
Low Cost ◽  
Rapid Development ◽  
Colorimetric Method ◽  
Antiviral Drug ◽  
Human Adenovirus ◽  
Human Adenoviruses ◽  
Direct Acting Antiviral ◽  
Optimal Drug

Currently, 90 different types of human adenoviruses (HAdV) are known, which have been classified into seven species from A to G and new adenovirus types continue to emerge. Antigenic diversity of viruses inhibits the process of creating universal vaccines and causes the development of resistance to direct-acting antiviral drugs. In addition to the rapid development of drug resistance, too narrow a range of existing drugs and a significant number of side effects limits the treatment of adenoviral infections. There is currently no specific etiotropic antiviral drug. Therefore, the development of new effective drugs and the selection of the optimal drug for the treatment of infections caused by adenoviruses remain relevant. The aim of the study was to investigate the antiviral properties of the drugs Nazoferon spray and Nazoferon drops in a model of human adenovirus serotype 3. Methods. Determination of cytotoxicity and antiviral action of drugs was performed by standard colorimetric method using MTT. The titer of the virus, synthesized in the presence of drugs was determined by the end point of dilution of the virus, which causes 50% development of the cytopathic effect of the virus on cells (СPE). Results. Low cytotoxicity of Nazoferon spray and Nazoferon drops (manufactured by JSC Farmak, Ukraine) was shown, CC50 is 53854 IU/ml and 54357 IU/ml, respectively. Quantitative and qualitative composition of excipients had no cytotoxic effect. In prophylactic regimens, interferon preparations did not inhibit the reproduction of adenovirus in vitro. Taking into account that most of the virions remain associated with the cells during the reproduction of adenovirus in the cell, we used test to determine infectivity lysates of infected and treated cells. The infectious titer of the synthesized HAdV3 was reduced by 3.2 log10 and 3.7 log10 for Nazoferon spray and drops, respectively. Conclusions. Nazoferon spray and drops can be recommended as anti-adenoviral drugs that block the reproduction of adenovirus, and due to their bioavailability and low cost have significant advantages in the treatment of acute respiratory infections (ARIs) caused by human adenoviruses.

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