In-silico screening and experimental validation reveal L-Adrenaline as anti-biofilm molecule against biofilm-associated protein (Bap) producing Acinetobacter baumannii

A combined computational and experimental methodology is developed to predict new materials that can reversibly produce oxygen for chemical looping combustion, and then promising candidates are selected for experimental validation of these predictions.

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B6. In silico screening and experimental validation of novel inhibitors of nitric oxide from a database of natural products derived from traditional chinese medicine

Nitric Oxide ◽

10.1016/j.niox.2007.09.039 ◽

2007 ◽

Vol 17 ◽

pp. 17

Author(s):

V.B. Konkimalla ◽

M. Blunder ◽

R. Bauer ◽

T. Efferth

Keyword(s):

Nitric Oxide ◽

Natural Products ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

In Silico ◽

Experimental Validation ◽

In Silico Screening

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Distribution of Four Biofilm Associated Gene among A. baumannii by in Silico-PCR

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i57b34062 ◽

2021 ◽

pp. 317-324

Author(s):

J. D. Monesh Babu ◽

A. S. Smiline Girija ◽

P. Sankar Ganesh ◽

J. Vijayashree Priyadharsini

Keyword(s):

Acinetobacter Baumannii ◽

In Silico ◽

Biofilm Formation ◽

Experimental Validation ◽

Pcr Amplification ◽

Opportunistic Pathogen ◽

Clinical Strains ◽

Oral Biofilms ◽

Different Strains ◽

In Silico Pcr

Background: A.baumannii is an opportunistic pathogen known for its efficient biofilm formation that is attributed for its virulence. Acinetobacter baumannii is an inhabitant of oral biofilms as well. Many gene operons are involved in the biofilm formation that need to be monitored frequently. Aim: The aim of the present study was to detect the distribution of four biofilm associated genes among A.baumannii. Materials and Methods: Four biofilm forming genes viz., bfms, ptk, pgaB, and fimH of A.baumannii were selected. Forward and reverse primers of those four genes were used for in-silico PCR amplification. 19 strains of A.baumannii set as default on the server were chosen and the amplicon bands were observed Results: The present investigation documents the distribution of four vital biofilm associated gene among 19 different strains of A.baumannii among which bfms was distributed at a higher frequency followed by pgaB and ptk Conclusion: The finding of the study suggests the presence of pgaB, bfms, ptk among the 19 different strains of A.baumannii. However further experimental validation must be done to frequently monitor the presence of the genes among the clinical strains of A.baumannii.

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Gold-Aptamer-Nanoconstructs Engineered to Detect Conserved Enteroviral Nucleic Acid Sequences

10.26434/chemrxiv.8312324.v1 ◽

2019 ◽

Author(s):

Veeren Chauhan ◽

Mohamed M Elsutohy ◽

C Patrick McClure ◽

Will Irving ◽

Neil Roddis ◽

...

Keyword(s):

Nucleic Acid ◽

In Silico ◽

Point Of Care ◽

Lateral Flow ◽

Nucleic Acid Sequence ◽

In Silico Screening ◽

Lateral Flow Assays ◽

Life Threatening ◽

Software And Hardware ◽

Nucleic Acid Sequences

Enteroviruses are a ubiquitous mammalian pathogen that can produce mild to life-threatening disease. Bearing this in mind, we have developed a rapid, accurate and economical point-of-care biosensor that can detect a nucleic acid sequences conserved amongst 96% of all known enteroviruses. The biosensor harnesses the physicochemical properties of gold nanoparticles and aptamers to provide colourimetric, spectroscopic and lateral flow-based identification of an exclusive enteroviral RNA sequence (23 bases), which was identified through in silico screening. Aptamers were designed to demonstrate specific complementarity towards the target enteroviral RNA to produce aggregated gold-aptamer nanoconstructs. Conserved target enteroviral nucleic acid sequence (≥ 1x10-7 M, ≥1.4×10-14 g/mL), initiates gold-aptamer-nanoconstructs disaggregation and a signal transduction mechanism, producing a colourimetric and spectroscopic blueshift (544 nm (purple) > 524 nm (red)). Furthermore, lateral-flow-assays that utilise gold-aptamer-nanoconstructs were unaffected by contaminating human genomic DNA, demonstrated rapid detection of conserved target enteroviral nucleic acid sequence (< 60 s) and could be interpreted with a bespoke software and hardware electronic interface. We anticipate our methodology will translate in-silico screening of nucleic acid databases to a tangible enteroviral desktop detector, which could be readily translated to related organisms. This will pave-the-way forward in the clinical evaluation of disease and complement existing strategies at overcoming antimicrobial resistance.

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Molecular Mechanisms of Several Novel Dipeptides with Angiotensin-Iconverting Enzyme Inhibitory Activity from In-silico Screening of Silkworm Pupae Protein

Current Pharmaceutical Biotechnology ◽

10.2174/138920101508140930153336 ◽

2014 ◽

Vol 15 (8) ◽

pp. 691-699 ◽

Cited By ~ 2

Author(s):

Wei Wang ◽

Yu Zhang ◽

Nan Wang ◽

Zuoyi Zhu

Keyword(s):

Inhibitory Activity ◽

In Silico ◽

Molecular Mechanisms ◽

In Silico Screening ◽

Silkworm Pupae

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Design and in-silico screening of Peptide Nucleic Acid (PNA) inspired novel pronucleotide scaffolds targeting COVID-19

Current Computer - Aided Drug Design ◽

10.2174/1573409916666200923143935 ◽

2020 ◽

Vol 16 ◽

Author(s):

Bichismita Sahu ◽

Santosh Kumar Behera ◽

Rudradip Das ◽

Tanay Dalvi ◽

Arnab Chowdhury ◽

...

Keyword(s):

Nucleic Acid ◽

In Silico ◽

Peptide Nucleic Acid ◽

Large Set ◽

Nonstructural Proteins ◽

In Silico Screening ◽

Replication Process ◽

Enveloped Virus ◽

Treatment Regimens ◽

Novel Coronavirus

Introduction: The outburst of the novel coronavirus COVID-19, at the end of December 2019 has turned itself into a pandemic taking a heavy toll on human lives. The causal agent being SARS-CoV-2, a member of the long-known Coronaviridae family, is a positive sense single-stranded enveloped virus and quite closely related to SARS-CoV. It has become the need of the hour to understand the pathophysiology of this disease, so that drugs, vaccines, treatment regimens and plausible therapeutic agents can be produced. Methods: In this regard, recent studies uncovered the fact that the viral genome of SARS-CoV-2 encodes nonstructural proteins like RNA dependent RNA polymerase (RdRp) which is an important tool for its transcription and replication process. A large number of nucleic acid based anti-viral drugs are being repurposed for treating COVID-19 targeting RdRp. Few of them are in the advanced stage of clinical trials including Remdesivir. While performing close investigation of the large set of nucleic acid based drugs, we were surprised to find that the synthetic nucleic acid backbone is explored very little or rare. Results: We have designed scaffolds derived from peptide nucleic acid (PNA) and subjected them for in-silico screening systematically. These designed molecules have demonstrated excellent binding towards RdRp. Compound 12 was found to possess similar binding affinity as Remdesivir with comparable pharmacokinetics. However, the in-silico toxicity prediction indicates compound 12 may be a superior molecule which can be explored further due to its excellent safety-profile with LD50 (12,000mg/kg) as opposed to Remdesivir (LD50 =1000mg/kg). Conclusion: Compound 12 falls in the safe category of class 6. Synthetic feasibility, equipotent binding and very low toxicity of this peptide nucleic acid derived compounds can serve as a leading scaffold to design, synthesize and evaluate many of similar compounds for the treatment of COVID-19.

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In silico screening of pyridoxine carbamates for Anti-Alzheimer’s activities

Central Nervous System Agents in Medicinal Chemistry ◽

10.2174/1871524920666201119144535 ◽

2020 ◽

Vol 20 ◽

Author(s):

Dnyaneshwar Baswar ◽

Abha Sharma ◽

Awanish Mishra

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

In Silico ◽

Neurodegenerative Disorder ◽

Biological Activities ◽

Cholinergic Neurons ◽

In Silico Screening ◽

In Silico Studies ◽

Bbb Permeability ◽

Ld50 Value

Background: Alzheimer’s disease (AD), an irreversible complex neurodegenerative disorder, is most common type of dementia, with progressive loss of cholinergic neurons. Based on the multi- factorial etiology of Alzheimer’s disease, novel ligands strategy appears as up-coming approach for the development of newer molecules against AD. This study is envisaged to investigate anti-Alzheimer’s potential of 10 synthesized compounds. The screening of compounds (1-10) was carried out using in silico techniques. Methods: For in silico screening of physicochemical properties of compounds molinspiration property engine v.2018.03, Swiss ADME online web-server and pkCSM ADME were used. For pharmacodynamic prediction PASS software while toxicity profile of compounds were analyzed through ProTox-II online software. Simultaneously, molecular docking analysis was performed on mouse AChE enzyme (PDB ID:2JGE, obtained from RSCB PDB) using Auto Dock Tools 1.5.6. Results: Based on in silico studies, compound 9 and 10 have been found to have better drug likeness, LD50 value, and better anti-Alzheimer’s, nootropic activities. However, these compounds had poor blood brain barrier (BBB) permeability. Compound 4 and 9 were predicted with better docking score for AChE enzyme. Conclusion: The outcome of in silico studies have suggested, out of various substitutions at different positions of pyridoxine-carbamate, compound 9 have shown promising drug likeness, with better safety and efficacy profile for anti-Alzheimer’s activity. However, BBB permeability appears as one the major limitation of all these compounds. Further studies are required to confirm its biological activities.

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