scholarly journals Cnicin as an Anti-SARS-CoV-2: An Integrated In Silico and In Vitro Approach for the Rapid Identification of Potential COVID-19 Therapeutics

Antibiotics ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 542
Author(s):  
Hani A. Alhadrami ◽  
Ahmed M. Sayed ◽  
Hossam M. Hassan ◽  
Khayrya A. Youssif ◽  
Yasser Gaber ◽  
...  
Keyword(s):  
Natural Products ◽  
In Silico ◽  
Structural Information ◽  
Chemical Constituents ◽  
Rapid Identification ◽  
Dependent Manner ◽  
Modeling Tools ◽  
Clinical Experiments

Since the emergence of the SARS-CoV-2 pandemic in 2019, it has remained a significant global threat, especially with the newly evolved variants. Despite the presence of different COVID-19 vaccines, the discovery of proper antiviral therapeutics is an urgent necessity. Nature is considered as a historical trove for drug discovery, especially in global crises. During our efforts to discover potential anti-SARS CoV-2 natural therapeutics, screening our in-house natural products and plant crude extracts library led to the identification of C. benedictus extract as a promising candidate. To find out the main chemical constituents responsible for the extract’s antiviral activity, we utilized recently reported SARS CoV-2 structural information in comprehensive in silico investigations (e.g., ensemble docking and physics-based molecular modeling). As a result, we constructed protein–protein and protein–compound interaction networks that suggest cnicin as the most promising anti-SARS CoV-2 hit that might inhibit viral multi-targets. The subsequent in vitro validation confirmed that cnicin could impede the viral replication of SARS CoV-2 in a dose-dependent manner, with an IC50 value of 1.18 µg/mL. Furthermore, drug-like property calculations strongly recommended cnicin for further in vivo and clinical experiments. The present investigation highlighted natural products as crucial and readily available sources for developing antiviral therapeutics. Additionally, it revealed the key contributions of bioinformatics and computer-aided modeling tools in accelerating the discovery rate of potential therapeutics, particularly in emergency times like the current COVID-19 pandemic.

scholarly journals AMPing Up the Search: A Structural and Functional Repository of Antimicrobial Peptides for Biofilm Studies, and a Case Study of Its Application to Corynebacterium striatum, an Emerging Pathogen

2021 ◽  
Vol 11 ◽  
Author(s):  
Shreeya Mhade ◽  
Stutee Panse ◽  
Gandhar Tendulkar ◽  
Rohit Awate ◽  
Yatindrapravanan Narasimhan ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
In Silico ◽  
Emerging Pathogen ◽  
Preference Scale ◽  
Modeling Tools ◽  
Interaction Models ◽  
Corynebacterium Striatum

Antimicrobial peptides (AMPs) have been recognized for their ability to target processes important for biofilm formation. Given the vast array of AMPs, identifying potential anti-biofilm candidates remains a significant challenge, and prompts the need for preliminary in silico investigations prior to extensive in vitro and in vivo studies. We have developed Biofilm-AMP (B-AMP), a curated 3D structural and functional repository of AMPs relevant to biofilm studies. In its current version, B-AMP contains predicted 3D structural models of 5544 AMPs (from the DRAMP database) developed using a suite of molecular modeling tools. The repository supports a user-friendly search, using source, name, DRAMP ID, and PepID (unique to B-AMP). Further, AMPs are annotated to existing biofilm literature, consisting of a vast library of over 10,000 articles, enhancing the functional capabilities of B-AMP. To provide an example of the usability of B-AMP, we use the sortase C biofilm target of the emerging pathogen Corynebacterium striatum as a case study. For this, 100 structural AMP models from B-AMP were subject to in silico protein-peptide molecular docking against the catalytic site residues of the C. striatum sortase C protein. Based on docking scores and interacting residues, we suggest a preference scale using which candidate AMPs could be taken up for further in silico, in vitro and in vivo testing. The 3D protein-peptide interaction models and preference scale are available in B-AMP. B-AMP is a comprehensive structural and functional repository of AMPs, and will serve as a starting point for future studies exploring AMPs for biofilm studies. B-AMP is freely available to the community at https://b-amp.karishmakaushiklab.com and will be regularly updated with AMP structures, interaction models with potential biofilm targets, and annotations to biofilm literature.

scholarly journals Trypanocidal Essential Oils: A Review

Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4568 ◽  
Author(s):  
Mayara Castro de Morais ◽  
Jucieudo Virgulino de Souza ◽  
Carlos da Silva Maia Bezerra Filho ◽  
Silvio Santana Dolabella ◽  
Damião Pergentino de Sousa
Keyword(s):  
Experimental Data ◽  
Natural Products ◽  
Essential Oils ◽  
Therapeutic Potential ◽  
Chemical Constituents ◽  
Mechanisms Of Action ◽  
New Drugs ◽  
Important Group

Trypanosomiases are diseases caused by parasitic protozoan trypanosomes of the genus Trypanosoma. In humans, this includes Chagas disease and African trypanosomiasis. There are few therapeutic options, and there is low efficacy to clinical treatment. Therefore, the search for new drugs for the trypanosomiasis is urgent. This review describes studies of the trypanocidal properties of essential oils, an important group of natural products widely found in several tropical countries. Seventy-seven plants were selected from literature for the trypanocidal activity of their essential oils. The main chemical constituents and mechanisms of action are also discussed. In vitro and in vivo experimental data show the therapeutic potential of these natural products for the treatment of infections caused by species of Trypanosoma.

scholarly journals Flexibility and mobility of SARS-CoV-2-related protein structures

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rudolf A. Römer ◽  
Navodya S. Römer ◽  
A. Katrine Wallis
Keyword(s):  
In Silico ◽  
Drug Targets ◽  
Large Scale ◽  
Structural Information ◽  
Protein Structures ◽  
Antiviral Drug ◽  
Docking Studies ◽  
Related Protein

AbstractThe worldwide CoVid-19 pandemic has led to an unprecedented push across the whole of the scientific community to develop a potent antiviral drug and vaccine as soon as possible. Existing academic, governmental and industrial institutions and companies have engaged in large-scale screening of existing drugs, in vitro, in vivo and in silico. Here, we are using in silico modelling of possible SARS-CoV-2 drug targets, as deposited on the Protein Databank (PDB), and ascertain their dynamics, flexibility and rigidity. For example, for the SARS-CoV-2 spike protein—using its complete homo-trimer configuration with 2905 residues—our method identifies a large-scale opening and closing of the S1 subunit through movement of the S$${}^\text{B}$$ B domain. We compute the full structural information of this process, allowing for docking studies with possible drug structures. In a dedicated database, we present similarly detailed results for the further, nearly 300, thus far resolved SARS-CoV-2-related protein structures in the PDB.

scholarly journals Applying Bioinformatic Platforms, In Vitro, and In Vivo Functional Assays in the Characterization of Genetic Variants in the GH/IGF Pathway Affecting Growth and Development

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2063
Author(s):  
Sabina Domené ◽  
Paula A. Scaglia ◽  
Mariana L. Gutiérrez ◽  
Horacio M. Domené
Keyword(s):  
In Silico ◽  
Growth And Development ◽  
Genetic Variant ◽  
Modeling Tools ◽  
In Vivo Models ◽  
Bioinformatic Tools ◽  
Functional Assays

Heritability accounts for over 80% of adult human height, indicating that genetic variability is the main determinant of stature. The rapid technological development of Next-Generation Sequencing (NGS), particularly Whole Exome Sequencing (WES), has resulted in the characterization of several genetic conditions affecting growth and development. The greatest challenge of NGS remains the high number of candidate variants identified. In silico bioinformatic tools represent the first approach for classifying these variants. However, solving the complicated problem of variant interpretation requires the use of experimental approaches such as in vitro and, when needed, in vivo functional assays. In this review, we will discuss a rational approach to apply to the gene variants identified in children with growth and developmental defects including: (i) bioinformatic tools; (ii) in silico modeling tools; (iii) in vitro functional assays; and (iv) the development of in vivo models. While bioinformatic tools are useful for a preliminary selection of potentially pathogenic variants, in vitro—and sometimes also in vivo—functional assays are further required to unequivocally determine the pathogenicity of a novel genetic variant. This long, time-consuming, and expensive process is the only scientifically proven method to determine causality between a genetic variant and a human genetic disease.

scholarly journals Preclinical Techniques to Investigate Exercise Training in Vascular Pathophysiology

2021 ◽  
Author(s):  
Gurneet Singh Sangha ◽  
Craig J. Goergen ◽  
Sushant M. Ranadive ◽  
Steven J. Prior ◽  
Alisa M Clyne
Keyword(s):  
In Silico ◽  
Cardiovascular Health ◽  
Dependent Manner ◽  
Preclinical Research ◽  
High Intensity Training ◽  
In Silico Studies ◽  
Tissue Systems ◽  
Arterial Plaques

Atherosclerosis is a dynamic process starting with endothelial dysfunction and inflammation and eventually leading to life-threatening arterial plaques. Exercise generally improves endothelial function in a dose-dependent manner by altering hemodynamics, specifically by increased arterial pressure, pulsatility, and shear stress. However, athletes who regularly participate in high-intensity training can develop arterial plaques, suggesting alternative mechanisms through which excessive exercise promotes vascular disease. Understanding the mechanisms that drive atherosclerosis in sedentary versus exercise states may lead to novel rehabilitative methods aimed at improving exercise compliance and physical activity. Preclinical tools, including in vitro cell assays, in vivo animal models, and in silico computational methods, broaden our capabilities to study the mechanisms through which exercise impacts atherogenesis, from molecular maladaptation to vascular remodeling. Here, we describe how preclinical research tools have and can be used to study exercise effects on atherosclerosis. We then propose how advanced bioengineering techniques can be used to address gaps in our current understanding of vascular pathophysiology, including integrating in vitro, in vivo, and in silico studies across multiple tissue systems and size scales. Improving our understanding of the anti-atherogenic exercise effects will enable engaging, targeted, and individualized exercise recommendations to promote cardiovascular health rather than treating cardiovascular disease that results from a sedentary lifestyle.

Natural Products as Potential Agents Against SARS-CoV and SARS-CoV-2

2021 ◽  
Vol 28 ◽  
Author(s):  
Joanda Paolla Raimundo e Silva ◽  
Chonny Alexander Herrera Acevedo ◽  
Thalisson Amorim de Souza ◽  
Renata Priscila Barros de Menezes ◽  
Zoe L. Sessions ◽  
...  
Keyword(s):  
Natural Products ◽  
In Silico ◽  
Principal Component ◽  
In Vivo Studies ◽  
In Vitro Assays ◽  
Future Research ◽  
Natural Substances ◽  
Effective Drugs

Background: Natural products are useful agents for the discovery of new lead-compounds and effective drugs to combat coronaviruses (CoV). Objective: The present work provides an overview of natural substances, plant extracts, and essential oils as potential antiSARS-CoV agents. In addition, this work evaluates their drug-like properties which are essential in the selection of compounds in order to accelerate the drug development process. Methods: The search was carried out using PubMed, ScienceDirect and SciFinder. Articles addressing plant-based natural products as potential SARS-CoV or SARS-CoV-2 agents within the last seventeen years were analyzed and selected. The descriptors for Chemometrics analyzes were obtained in alvaDesc and the principal component analyzes (PCA) were carried out in SIMCA version 13.0. Results: Based on in vitro assays and computational analyzes, this review covers twenty nine medicinal plant species and more than 300 isolated substances as potential anti-coronavirus agents. Among them, flavonoids and terpenes were the most promising compound classes. In silico analyses of drug-like properties corroborate these findings and indicate promising candidates for in vitro and in vivo studies to validate their activity. Conclusion: This paper highlights the role of ethnopharmacology in drug discovery and simulates the use of integrative (in silico/ in vitro) and chemocentric approaches to strengthen current studies and guide future research in the field of antivirals agents.

scholarly journals In Silico Predictions of Endocrine Disruptors Properties

Endocrinology ◽  
2019 ◽  
Vol 160 (11) ◽  
pp. 2709-2716 ◽  
Author(s):  
Melanie Schneider ◽  
Jean-Luc Pons ◽  
Gilles Labesse ◽  
William Bourguet
Keyword(s):  
Biological Activity ◽  
Endocrine Disruptors ◽  
In Silico ◽  
Chemical Structure ◽  
Structural Information ◽  
Broad Class ◽  
Computer Assisted ◽  
Screening Methods

Abstract Endocrine-disrupting chemicals (EDCs) are a broad class of molecules present in our environment that are suspected to cause adverse effects in the endocrine system by interfering with the synthesis, transport, degradation, or action of endogenous ligands. The characterization of the harmful interaction between environmental compounds and their potential cellular targets and the development of robust in vivo, in vitro, and in silico screening methods are important for assessment of the toxic potential of large numbers of chemicals. In this context, computer-aided technologies that will allow for activity prediction of endocrine disruptors and environmental risk assessments are being developed. These technologies must be able to cope with diverse data and connect chemistry at the atomic level with the biological activity at the cellular, organ, and organism levels. Quantitative structure–activity relationship methods became popular for toxicity issues. They correlate the chemical structure of compounds with biological activity through a number of molecular descriptors (e.g., molecular weight and parameters to account for hydrophobicity, topology, or electronic properties). Chemical structure analysis is a first step; however, modeling intermolecular interactions and cellular behavior will also be essential. The increasing number of three-dimensional crystal structures of EDCs’ targets has provided a wealth of structural information that can be used to predict their interactions with EDCs using docking and scoring procedures. In the present review, we have described the various computer-assisted approaches that use ligands and targets properties to predict endocrine disruptor activities.

scholarly journals In Silico Approaches to Identify Polyphenol Compounds as α-Glucosidase and α-Amylase Inhibitors against Type-II Diabetes

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1877
Author(s):  
Jirawat Riyaphan ◽  
Dinh-Chuong Pham ◽  
Max K. Leong ◽  
Ching-Feng Weng
Keyword(s):  
Natural Products ◽  
In Silico ◽  
Type Ii Diabetes ◽  
Postprandial Glucose ◽  
Type Ii Diabetes Mellitus ◽  
Type Ii ◽  
Amino Acid Residues ◽  
Discovery Studio

Type-II diabetes mellitus (T2DM) results from a combination of genetic and lifestyle factors, and the prevalence of T2DM is increasing worldwide. Clinically, both α-glucosidase and α-amylase enzymes inhibitors can suppress peaks of postprandial glucose with surplus adverse effects, leading to efforts devoted to urgently seeking new anti-diabetes drugs from natural sources for delayed starch digestion. This review attempts to explore 10 families e.g., Bignoniaceae, Ericaceae, Dryopteridaceae, Campanulaceae, Geraniaceae, Euphorbiaceae, Rubiaceae, Acanthaceae, Rutaceae, and Moraceae as medicinal plants, and folk and herb medicines for lowering blood glucose level, or alternative anti-diabetic natural products. Many natural products have been studied in silico, in vitro, and in vivo assays to restrain hyperglycemia. In addition, natural products, and particularly polyphenols, possess diverse structures for exploring them as inhibitors of α-glucosidase and α-amylase. Interestingly, an in silico discovery approach using natural compounds via virtual screening could directly target α-glucosidase and α-amylase enzymes through Monte Carto molecular modeling. Autodock, MOE-Dock, Biovia Discovery Studio, PyMOL, and Accelrys have been used to discover new candidates as inhibitors or activators. While docking score, binding energy (Kcal/mol), the number of hydrogen bonds, or interactions with critical amino acid residues have been taken into concerning the reliability of software for validation of enzymatic analysis, in vitro cell assay and in vivo animal tests are required to obtain leads, hits, and candidates in drug discovery and development.

scholarly journals Immune Modulatory Activities of Arginyl-Fructose (AF) and AF-Enriched Natural Products in In-Vitro and In-Vivo Animal Models

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2251
Author(s):  
Jin-A Yu ◽  
Jung-Yun Lee ◽  
Tae Yang Kim ◽  
Hanna Kang ◽  
Su-Young Lee ◽  
...  
Keyword(s):  
Natural Products ◽  
Treated Group ◽  
Dependent Manner ◽  
Red Ginseng ◽  
Mice Model ◽  
Mouse Splenocytes ◽  
Higher Weights ◽  
In Vivo Animal Models

The immune system plays an important role in maintaining body homeostasis. Recent studies on the immune-enhancing effects of ginseng saponins have revealed more diverse mechanisms of action. Maillard reaction that occurs during the manufacturing processes of red ginseng produces a large amount of Amadori rearrangement compounds (ARCs), such as arginyl-fructose (AF). The antioxidant and anti-hyperglycemic effects of AF have been reported. However, the possible immune enhancing effects of non-saponin ginseng compounds, such as AF, have not been investigated. In this study the effects of AF and AF-enriched natural product (Ginofos, GF) on proliferation of normal mouse splenocytes were evaluated in vitro and male BALB/c mice models. The proliferation of splenocytes treated with mitogens (concanavalin A, lipopolysaccharide) were further increased by addition of AF (p < 0.01) or GF (p < 0.01), in a dose dependent manner. After the 10 days of oral administration of compounds, changes in weights of spleen and thymus, serum immunoglobulin, and expression of cytokines were measured as biomarkers of immune-enhancing potential in male BALB/c mice model. The AF or GF treated groups had higher weights of the thymus (0.94 ± 0.25 and 0.86 ± 0.18, p < 0.05, respectively) than that of cyclophosphamide treated group (0.59 ± 0.18). This result indicates that AF or AF-enriched extract (GF) increased humoral immunity against CY-induced immunosuppression. In addition, immunoglobulin contents and expression of cytokines including IgM (p < 0.01), IgG (p < 0.05), IL-2 (p < 0.01), IL-4 (p < 0.01), IL-6 (p < 0.01), and IFN-γ (p < 0.05) were also significantly increased by supplementation of AF or GF. These results indicate that AF has immune enhancing effects by activation of adaptive immunity via increase of expression of immunoglobulins and cytokines such as IgM, IgG, IL-2, IL-4, IL-6 and thereby proliferating the weight of thymus. Our findings provide a pharmacological rationale for AF-enriched natural products such as ginseng and red ginseng that can possibly have immune-enhancement potential and should be further evaluated.

scholarly journals Aromatic Herbs, Medicinal Plant-Derived Essential Oils, and Phytochemical Extracts as Potential Therapies for Coronaviruses: Future Perspectives

Plants ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 800 ◽  
Author(s):  
Mohamed Nadjib Boukhatem ◽  
William N. Setzer
Keyword(s):  
Natural Products ◽  
Essential Oils ◽  
Viral Entry ◽  
Chemical Constituents ◽  
Herbal Medicines ◽  
Antiviral Drugs ◽  
Medicinal And Aromatic Plants ◽  
Aromatic Herbs

After its recent discovery in patients with serious pneumonia in Wuhan (China), the 2019 novel coronavirus (2019-nCoV), named also Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has spread quickly. Unfortunately, no drug or vaccine for treating human this coronavirus infection is available yet. Numerous options for controlling or preventing emerging 2019-nCoV infections may be predicted, including vaccines, interferon therapies, and small-molecule drugs. However, new interventions are likely to require months to years to develop. In addition, most of the existing antiviral treatments frequently lead to the development of viral resistance combined with the problem of side effects, viral re-emergence, and viral dormancy. The pharmaceutical industry is progressively targeting phytochemical extracts, medicinal plants, and aromatic herbs with the aim of identifying lead compounds, focusing principally on appropriate alternative antiviral drugs. Spices, herbal medicines, essential oils (EOs), and distilled natural products provide a rich source of compounds for the discovery and production of novel antiviral drugs. The determination of the antiviral mechanisms of these natural products has revealed how they interfere with the viral life cycle, i.e., during viral entry, replication, assembly, or discharge, as well as virus-specific host targets. Presently, there are no appropriate or approved drugs against CoVs, but some potential natural treatments and cures have been proposed. Given the perseverance of the 2019-nCoV outbreak, this review paper will illustrate several of the potent antiviral chemical constituents extracted from medicinal and aromatic plants, natural products, and herbal medicines with recognized in vitro and in vivo effects, along with their structure–effect relationships. As this review shows, numerous potentially valuable aromatic herbs and phytochemicals are awaiting assessment and exploitation for therapeutic use against genetically and functionally different virus families, including coronaviruses.

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