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

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.

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

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

<p>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<sup>-7</sup> M, ≥1.4×10<sup>-14</sup> 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.</p>

Screening of phytochemicals from Curcuma longa for their inhibitory activity on SARS-CoV-2: An in-silico study

2021 ◽  
Vol 19 ◽  
Author(s):  
Preeya Negi ◽  
Lalita Das ◽  
Surya Prakash ◽  
Vaishali M. Patil
Keyword(s):  
Drug Discovery ◽  
In Silico ◽  
Curcuma Longa ◽  
Docking Studies ◽  
Primary Objective ◽  
In Silico Screening ◽  
Rational Drug ◽  
In Silico Study ◽  
Speed Up ◽  
Novel Coronavirus

Introduction: Natural products or phytochemicals have always been useful as effective therapeutics and for providing the lead for rational drug discovery approaches specific to anti-viral therapeutics. Methods: The ongoing pandemic caused by novel coronavirus has created a demand for effective therapeutics. Thus, to achieve the primary objective to search for effective anti-viral therapeutics, in silico screening of phytochemicals present in Curcuma longa extract (ex. Curcumin) has been planned. Results: The present work involves the evaluation of ADME properties and molecular docking studies. Conclusion: The application of rationalized drug discovery approaches to screen the diverse natural resources will speed up the anti-COVID drug discovery efforts and benefit the global community.

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

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

<p>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<sup>-7</sup> M, ≥1.4×10<sup>-14</sup> 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.</p>

scholarly journals In silico screening of mint leaves compound (Mentha piperita L.) as a potential inhibitor of SARS-CoV-2

2021 ◽  
pp. 81-86
Author(s):  
Diana Serlahwaty ◽  
Cindy Giovani
Keyword(s):  
Amino Acids ◽  
In Silico ◽  
Mentha Piperita ◽  
The Novel ◽  
In Silico Screening ◽  
Comparison Results ◽  
Study Results ◽  
Herbal Plants ◽  
The One ◽  
Novel Coronavirus

Introduction: The novel coronavirus in Wuhan, China, was identified at the end of December 2019 and resulted in a global outbreak. Therefore, it is necessary to perform screening of compounds in herbal plants with antiviral potential against COVID-19. Mint leaves (Mentha piperita L.) were reported as one of the proposed samples, and this study was performed in silico to evaluate the antiviral activity of the content. Methods: The proposed mechanism of action includes the inhibition of SARS-CoV-2 proteins from binding with the receptor. Subsequently, several receptors associated with SARS-CoV-2 were validated, and the one with the code PDB 5R7Y and an RMSD value of 1.9974 Å was obtained using the YASARA application. This study was performed on 15 virtual mint leaves and five previously studied comparison compounds with inhibitory capacity. Therefore, docking started with the PLANTS application, and the results were visualised using PyMol to further identify the amino acids contained in the ligand, while the statistical t-test was used for comparison. Results: The study results showed the existence of active compounds in mint leaves, including rutin, hesperidin, and isorhoifolin.

scholarly journals In silico screening of Moroccan medicinal plants with the ability to directly inhibit the novel coronavirus, SARS-CoV-2

2020 ◽  
Author(s):  
Reda Ben Mrid ◽  
Najat Bouchmaa ◽  
Imad Kabach ◽  
Mansour Sobeh ◽  
Abdelmajid Zyad ◽  
...  
Keyword(s):  
Medicinal Plants ◽  
In Silico ◽  
Literature Search ◽  
Natural Compounds ◽  
The Novel ◽  
In Silico Screening ◽  
Adme Properties ◽  
Orally Bioavailable ◽  
Novel Coronavirus ◽  
Natural Inhibitors

Abstract In the present study, we investigated natural compounds contained in Moroccan medicinal plants and that might be used as natural inhibitors of the novel coronavirus, SARS-CoV-2, that causes coronavirus disease 2019 (COVID-19). We first performed a literature search for natural inhibitors of SARS or MERS coronaviruses. We then selected natural compounds that have been biologically tested and confirmed to possess anti-coronavirus activity. Subsequently, we used a molecular docking to determine whether the selected molecules could interact with the virus proteins. The compounds selected from virtual screening were then subjected to an in-silico analysis of absorption, distribution, metabolism and excretion (ADME) properties to select only natural compounds that could be orally bioavailable. Thereafter, a second search has been launched to select Moroccan medicinal plants that contain at least 3 molecules from those natural compounds. As results, among 41 natural inhibitors of SARS or MERS coronaviruses, only 13 have been successfully passed the ADME filtering. These molecules, showed abilities to interact with the novel coronavirus as it was predicted. Using these molecules and based on the data extracted from literature, 29 Moroccan medicinal plants have been found to contain at least 3 of these coronavirus inhibitors. Therefore, the medicinal plants selected in this study might contain direct anti-SARS-CoV-2 compounds.

scholarly journals In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus

2020 ◽  
Vol 18 (2) ◽  
pp. 152-158 ◽  
Author(s):  
Deng-hai Zhang ◽  
Kun-lun Wu ◽  
Xue Zhang ◽  
Sheng-qiong Deng ◽  
Bin Peng
Keyword(s):  
In Silico ◽  
Herbal Medicines ◽  
In Silico Screening ◽  
Chinese Herbal Medicines ◽  
Chinese Herbal ◽  
Novel Coronavirus

scholarly journals Gold–Oligonucleotide Nanoconstructs Engineered to Detect Conserved Enteroviral Nucleic Acid Sequences

Biosensors ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 238
Author(s):  
Veeren M. Chauhan ◽  
Mohamed M. Elsutohy ◽  
C. Patrick McClure ◽  
William L. 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 ubiquitous mammalian pathogens that can produce mild to life-threatening disease. We developed a multimodal, rapid, accurate and economical point-of-care biosensor that can detect nucleic acid sequences conserved amongst 96% of all known enteroviruses. The biosensor harnesses the physicochemical properties of gold nanoparticles and oligonucleotides to provide colourimetric, spectroscopic and lateral flow-based identification of an exclusive enteroviral nucleic acid sequence (23 bases), which was identified through in silico screening. Oligonucleotides were designed to demonstrate specific complementarity towards the target enteroviral nucleic acid to produce aggregated gold–oligonucleotide nanoconstructs. The conserved target enteroviral nucleic acid sequence (≥1 × 10−7 M, ≥1.4 × 10−14 g/mL) initiates gold–oligonucleotide nanoconstruct 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–oligonucleotide 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 that 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 to overcome antimicrobial resistance.

In silico screening of FDA approved drugs predicts the therapeutic potentials of Antibiotic drugs against the papain like protease of SARS-CoV-2

2021 ◽  
pp. 4035-4039
Author(s):  
Vipul Kumar ◽  
Sudhakar Kancharla ◽  
Manoj Kumar Jena
Keyword(s):  
In Silico ◽  
Computational Study ◽  
Docking Study ◽  
Wild Type ◽  
In Silico Screening ◽  
Antibiotic Drugs ◽  
Experimental Validations ◽  
Novel Coronavirus ◽  
Approved Drugs ◽  
Fda Approved Drugs

Since the outbreak of severe acute respiratory syndrome corona Virus -2 (SARS-CoV-2) has happened in December 2019 in Wuhan, China, the cases of novel coronavirus disease (COVID-19) is rapidly increasing worldwide. In the absence of specific drugs against COVID-19, the fast and reliable choice would be repurposing of existing drugs. Here, we have chosen one of the crucial enzymes of the SARS-CoV-2, Papain like protease (PLpro) and its mutant C111S for the structure-based in-silico screening of the FDA approved drugs. Firstly, the alignment of the wild type and mutant PLpro was done, and no significant change in the global structure was observed. Then based on the docking study, we have reported the best 3 compounds against a mutant and wild type PLpro. These lead compounds include amikacin and mafenide, which are well-known antibiotics. The binding affinity, as well as number of polar and non-polar interactions, indicates their potential against the PLpro. This computational study strongly suggests the experimental validations of the predicted compounds for a confident claim.

Sign in / Sign up

Export Citation Format

Share Document