A Highly Potent SARS-CoV-2 Blocking Lectin Protein

COVID-19 pandemic effected more than 180 million people around the globe causing more than four million deaths as of July 2021. Sars-CoV-2, the new coronavirus, has been identified as the primary cause of the infection. The number of vaccinated people is increasing however prophylactic drugs are highly demanded to ensure a secure social contact. There have been a number of drug molecules repurposed to fight against Sars-CoV-2, however the proofs for the effectiveness of these drug candidates is limited. Here we demonstrated griffithsin (GRFT), a lectin protein, to block the entry of the Sars-CoV2 into the Vero6 cell lines and IFNAR-/- mouse models by attaching to spike protein of the Sars-CoV-2. Given the current mutation frequency of the Sars-CoV-2 we believe that GRFT protein-based drugs will have a high impact in preventing the transmission both on Wuhan strain as well as any other emerging variants including delta variant causing high speed spread of COVID-19.

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Fast Prediction of Binding Affinities of the SARS-CoV-2 Spike Protein Mutant N501Y (UK Variant) with ACE2 and Miniprotein Drug Candidates

The Journal of Physical Chemistry B ◽

10.1021/acs.jpcb.1c00869 ◽

2021 ◽

Author(s):

Alexander H. Williams ◽

Chang-Guo Zhan

Keyword(s):

Spike Protein ◽

Binding Affinities ◽

Drug Candidates ◽

Fast Prediction

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The Position of ADME Predictions in Multi-Objective QSAR

International Journal of Quantitative Structure-Property Relationships ◽

10.4018/ijqspr.2021010101 ◽

2021 ◽

Vol 6 (1) ◽

pp. 1-8

Author(s):

Anna Tsantili-Kakoulidou

Keyword(s):

Drug Efficacy ◽

Clinical Development ◽

Efficacy And Safety ◽

Huge Amount ◽

Multi Objective ◽

Drug Candidates ◽

Drug Molecules ◽

Qsar Models ◽

Adme Properties ◽

Single Objective

ADME properties and toxicity predictions play an essential role in prioritization and optimization of drug molecules. According to recent statistics, drug efficacy and safety are principal reasons for drug failure. In this perspective, the position of ADME predictions in the evolution of traditional QSAR from the single objective of biological activity to a multi-task concept is discussed. The essential features of ADME and toxicity QSAR models are highlighted. Since such models are applied to prioritize existing or virtual project compounds with already established or predicted target affinity, a mechanistic interpretation, although desirable, is not a primary goal. However, a broad applicability domain is crucial. A future challenge with multi-objective QSAR is to adapt to the realm of big data by integrating techniques for the exploitation of the continuously increasing number of ADME data and the huge amount of clinical development endpoints for the sake of efficacy and safety of new drug candidates.

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Potential Drug Candidates for SARS-CoV-2 Using Computational Screening and Enhanced Sampling Methods

10.26434/chemrxiv.12254135.v1 ◽

2020 ◽

Author(s):

Sadanandam Namsani ◽

Debabrata Pramanik ◽

Mohd Aamir Khan ◽

Sudip Roy ◽

Jayant Singh

Keyword(s):

Free Energy ◽

High Performance ◽

Search Space ◽

Computational Method ◽

Enhanced Sampling ◽

Free Energy Surface ◽

Drug Candidates ◽

Drug Molecules ◽

Computational Screening ◽

Graphical Processing

<div><div><div><p>Here we report new chemical entities that are highly specific in binding towards the 3-chymotrypsin- like cysteine protease (3CLpro) protein present in the novel SARS-CoV2 virus. The viral 3CLpro</p><p>protein controls coronavirus replication. Therefore, 3CLpro is identified as a target for drug molecules. We have implemented an enhanced sampling method in combination with molecular dynamics and docking to bring down the computational screening search space to four molecules that could be synthesised and tested against COVID-19. Our computational method is much more robust than any other method available for drug screening e.g., docking, because of sampling of the free energy surface of the binding site of the protein (including the ligand) and use of explicit solvent. We have considered all possible interactions between all the atoms present in the protein, ligands, and water. Using high performance computing with graphical processing units we are able to perform large number of simulations within a month's time and converge to 4 most strongly bound ligands (by free energy and other scores) from a set of 17 ligands with lower docking scores. Based on our results and analysis, we claim with high confidence, that we have identified four potential ligands. Out of those, one particular ligand is the most promising candidate, based on free energy data, for further synthesis and testing against SARS-CoV-2 and might be effective for the cure of COVID-19.</p></div></div></div>

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Exploration on the Drug Solubility Enhancement in Aqueous Medium with the Help of Endo-Functionalized Molecular Tubes: A Computational Approach

Physical Chemistry Chemical Physics ◽

10.1039/d1cp01187a ◽

2021 ◽

Author(s):

Rabindranath Paul ◽

Sandip Paul

Keyword(s):

Pharmaceutical Industry ◽

Aqueous Medium ◽

Aqueous Solubility ◽

Solubility Enhancement ◽

Computational Approach ◽

Drug Solubility ◽

Drug Candidates ◽

Drug Molecules ◽

Molecular Tubes

One major problem in the pharmaceutical industry is the aqueous solubility of newly developed orally administered drug candidates. More than 50 % of the newly developed drug molecules suffer from...

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Virtual Screening of Phyto Chemicals Against SARS-CoV-2 Targets

International Journal of Quantitative Structure-Property Relationships ◽

10.4018/ijqspr.2021070105 ◽

2021 ◽

Vol 6 (3) ◽

pp. 61-76

Author(s):

Shahanas Naisam ◽

Vidhya V. S. ◽

Suvanish Kumar ◽

Nidhin Sreekumar

Keyword(s):

Dynamics Simulation ◽

Spike Protein ◽

Ligand Interaction ◽

Docking Analysis ◽

Drug Molecules ◽

In Vivo Analysis ◽

Protein Ligand Interaction ◽

The Stability ◽

3Cl Protease

The COVID-19 pandemic wave has recommenced and is spreading like wildfire across the globe. The well-reported antiviral potency of phyto compounds could offer potential drug molecules for the current predicament. The present study analyses the molecular interaction of selected phyto compounds and SARS-CoV-2 molecular target proteins, namely spike protein, RNA-dependent RNA polymerase, 3C-like proteases, and papain-like protease. Ten newly modeled ligands were also considered for the study. Molecular docking analysis was carried out independently using MOE, AutoDock Vina, Schrodinger-Glide, and the stability of protein-ligand interaction was validated through molecular dynamics simulation. Petunidin interacts with spike protein resulting in a good Gscore, binding energy, and H-bond interaction. Also, alions, letestuianin-A, (+)-pinitol show better interaction with RdRp, 3CL-protease, and papain-like protease, respectively. The presented work screens through 2314 ligands to yield top-ranked molecules which could be taken up to develop potential lead molecules via in-vivo analysis.

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Pan-HDAC Inhibitors Promote Tau Aggregation by Increasing the Level of Acetylated Tau

International Journal of Molecular Sciences ◽

10.3390/ijms20174283 ◽

2019 ◽

Vol 20 (17) ◽

pp. 4283 ◽

Cited By ~ 3

Author(s):

Hyeanjeong Jeong ◽

Seulgi Shin ◽

Jun-Seok Lee ◽

Soo Hyun Lee ◽

Ja-Hyun Baik ◽

...

Keyword(s):

Side Effects ◽

Mouse Models ◽

Cognitive Abilities ◽

Therapeutic Strategy ◽

Hdac Inhibitors ◽

Tau Pathology ◽

Drug Candidates ◽

Promising Target ◽

Epigenetic Remodeling ◽

Tau Aggregation

Epigenetic remodeling via histone acetylation has become a popular therapeutic strategy to treat Alzheimer’s disease (AD). In particular, histone deacetylase (HDAC) inhibitors including M344 and SAHA have been elucidated to be new drug candidates for AD, improving cognitive abilities impaired in AD mouse models. Although emerged as a promising target for AD, most of the HDAC inhibitors are poorly selective and could cause unwanted side effects. Here we show that tau is one of the cytosolic substrates of HDAC and the treatment of HDAC inhibitors such as Scriptaid, M344, BML281, and SAHA could increase the level of acetylated tau, resulting in the activation of tau pathology.

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Mechanism of Parameters Variation about Electronic Components Subjected to High Impact Loads

Applied Mechanics and Materials ◽

10.4028/www.scientific.net/amm.44-47.256 ◽

2010 ◽

Vol 44-47 ◽

pp. 256-259 ◽

Cited By ~ 1

Author(s):

Bo Li ◽

Ya Zhang ◽

Hong Xiang Zhang

Keyword(s):

Data Collection ◽

Stress Level ◽

Main Parameter ◽

High Speed ◽

Dynamic Testing ◽

High Impact ◽

Impact Loads ◽

Electronic Components ◽

Collection System ◽

High Speed Data

Large quantity dynamic testing experiments are carried out to testing the parameter of electronic components in high over loading impact condition with a standard hammer machine and a high speed data collection system. And the experiments were performed for about 5000 times to more than 30 types of resistors, capacitors, transistors to test their main parameter in different stress level and fixing mode. The parameter of some electronic components appears more or less unstable, namely temporary failure, and it is sensitive to different stress level and impact direct in experiments, which can offer important value of references for reliability lifespan.

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Cyclodextrin-Containing Polymers: Versatile Platforms of Drug Delivery Materials

Journal of Drug Delivery ◽

10.1155/2012/262731 ◽

2012 ◽

Vol 2012 ◽

pp. 1-17 ◽

Cited By ~ 33

Author(s):

Jeremy D. Heidel ◽

Thomas Schluep

Keyword(s):

Biological Properties ◽

Covalent Attachment ◽

Molecular Architecture ◽

Efficacy And Safety ◽

Future Directions ◽

Drug Candidates ◽

Drug Molecules ◽

Look Ahead ◽

Physicochemical And Biological Properties ◽

Potential Therapeutics

Nanoparticles are being widely explored as potential therapeutics for numerous applications in medicine and have been shown to significantly improve the circulation, biodistribution, efficacy, and safety profiles of multiple classes of drugs. One leading class of nanoparticles involves the use of linear, cyclodextrin-containing polymers (CDPs). As is discussed in this paper, CDPs can incorporate therapeutic payloads into nanoparticles via covalent attachment of prodrug/drug molecules to the polymer (the basis of the Cyclosert platform) or by noncovalent inclusion of cationic CDPs to anionic, nucleic acid payloads (the basis of the RONDEL platform). For each of these two approaches, we review the relevant molecular architecture and its rationale, discuss the physicochemical and biological properties of these nanoparticles, and detail the progress of leading drug candidates for each that have achieved clinical evaluation. Finally, we look ahead to potential future directions of investigation and product candidates based upon this technology.

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Behavior of Soft Spheres During Impact by High-Speed Photography

Journal of Engineering Materials and Technology ◽

10.1115/1.3225621 ◽

1983 ◽

Vol 105 (1) ◽

pp. 67-73 ◽

Cited By ~ 5

Author(s):

Yoichi Tatara

Keyword(s):

Deformation Process ◽

High Speed ◽

High Impact ◽

High Speed Photography ◽

Tennis Ball ◽

Hertz Model ◽

Hertz Theory ◽

Soft Spheres ◽

Almost All ◽

The Impact

Previously, it has been verified experimentally for durations of impact that the Hertz theory (the quasi-statical theory) holds during impact of spheres without any exception. However, no measurement of duration of impact has been presented for spheres of materials other than metal. This study presents exceptional cases of impacts of spheres during which the Hertz model does not directly hold. By the use of a high-speed camera running at a speed of 5000 frames/s, durations of impact are measured directly for impacts of two solid rubber spheres of the same size and content and impacts of a soft ball (Japanese type-soft tennis ball) on a rigid foundation. As a result, the measured durations of impact in the two impacting cases are found to be decreased as the impact velocity is increased, similar in tendency to durations of impact of elastic metal spheres during which the Hertz theory holds. However, the measured durations of impact are found to be clearly shorter than results calculated according to the Hertz theory, approximately half in the former impacts at high impact velocities, and about 70 percent of the Hertzian results in the latter impacts at almost all impact velocities. Deformation process of the ball impacting on the foundation is also presented to indicate both durations in the compressive process and the restitution one to be shorter than those expected by the Hertz theory. The other results observed on the films are noted to investigate the origin of the great discrepancies between the measured and Hertzian durations (that is, the impacting mechanism of the rubber spheres or the rubber ball packed with air treated here).

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