Discovery of a Low Toxicity O-GlcNAc Transferase (OGT) Inhibitor by Structure-based Virtual Screening of Natural Products

Abstract Background: The novel coronavirus (2019-nCoV) causes a severe respiratory illness that was unknown in the human before. Its alarmingly quick transmission to many countries across the world resulted in a worldwide health emergency. It has caused a notable percentage of morbidity and mortality. Therefore, an imminent need for drugs to combat this disease has been increased. Global collaborative efforts from scientists are underway to find a therapy to treat infections and reduce death cases. Herbal medicines and purified natural products have been reported to have antiviral activity against Coronaviruses (CoVs).Methods: In this study, a High Throughput Virtual Screening (HTVS) protocol was used as a fast method on the discovery of novel drug candidates as the COVID-19 main protease inhibitors. Over 180,000 natural product-based compounds were obtained from the ZINC database and virtually screened against the COVID-19 main protease. In this study, the Glide docking program was applied for high throughput virtual screening. Extra precision (XP) and in a combination of Prime module, induced-fit docking (IFD) approach was also used. Additionally, the ADME properties of all compounds were analyzed, and the final selection was carried out based on the Lipinski rule of five. Results: The nineteen compounds were selected and introduced as new potential inhibitors. The compound ZINC08765174 (1-[3-(1H-indol-3-yl) propanoyl]-N-(4-phenylbutan-2-yl)piperidine-3-carboxamide) showed a strong binding affinity (-11.5 kcal/mol) to the crucial residues of COVID-19 main protease comparing to peramivir (-9.8 kcal/mol) as a positive control.Conclusions: The excellent ADME properties proposed the opportunity of this compound to be a promising candidate for the treatment of COVID-19.

Download Full-text

Virtual screening for the discovery of bioactive natural products

Progress in Drug Research - Natural Compounds as Drugs Volume I ◽

10.1007/978-3-7643-8117-2_6 ◽

2008 ◽

pp. 211-249 ◽

Cited By ~ 39

Author(s):

Judith M. Rollinger ◽

Hermann Stuppner ◽

Thierry Langer

Keyword(s):

Natural Products ◽

Virtual Screening ◽

Bioactive Natural Products

Download Full-text

Review of Alternative Solvents for Green Extraction of Food and Natural Products: Panorama, Principles, Applications and Prospects

Molecules ◽

10.3390/molecules24163007 ◽

2019 ◽

Vol 24 (16) ◽

pp. 3007 ◽

Cited By ~ 42

Author(s):

Chemat ◽

Abert Vian ◽

Ravi ◽

Khadhraoui ◽

Hilali ◽

...

Keyword(s):

Natural Products ◽

Current Knowledge ◽

Green Solvents ◽

Food Ingredients ◽

Green Extraction ◽

Alternative Solvents ◽

Low Toxicity ◽

Extraction Processes ◽

Extraction Cycle ◽

Almost All

In recent years, almost all extraction processes in the perfume, cosmetic, pharmaceutical, food ingredients, nutraceuticals, biofuel and fine chemical industries rely massively on solvents, the majority of which have petroleum origins. The intricate processing steps involved in the industrial extraction cycle makes it increasingly difficult to predict the overall environmental impact; despite the tremendous energy consumption and the substantial usage of solvents, often the yields are indicated in decimals. The ideal alternative solvents suitable for green extraction should have high solvency, high flash points with low toxicity and low environmental impacts, be easily biodegradable, obtained from renewable (non-petrochemical) resources at a reasonable price and should be easy to recycle without any deleterious effect to the environment. Finding the perfect solvent that meets all the aforementioned requirements is a challenging task, thus the decision for the optimum solvent will always be a compromise depending on the process, the plant and the target molecules. The objective of this comprehensive review is to furnish a vivid picture of current knowledge on alternative, green solvents used in laboratories and industries alike for the extraction of natural products focusing on original methods, innovation, protocols, and development of safe products.

Download Full-text

Acetylcholinesterase Inhibitory Activity of Scopolin and Scopoletin Discovered by Virtual Screening of Natural Products†

Journal of Medicinal Chemistry ◽

10.1021/jm049655r ◽

2004 ◽

Vol 47 (25) ◽

pp. 6248-6254 ◽

Cited By ~ 123

Author(s):

Judith M. Rollinger ◽

Ariane Hornick ◽

Thierry Langer ◽

Hermann Stuppner ◽

Helmut Prast

Keyword(s):

Natural Products ◽

Virtual Screening ◽

Inhibitory Activity ◽

Acetylcholinesterase Inhibitory Activity

Download Full-text

Nanosystems for the Encapsulation of Natural Products: The Case of Chitosan Biopolymer as a Matrix

Pharmaceutics ◽

10.3390/pharmaceutics12070669 ◽

2020 ◽

Vol 12 (7) ◽

pp. 669 ◽

Cited By ~ 4

Author(s):

Anastasia Detsi ◽

Eleni Kavetsou ◽

Ioanna Kostopoulou ◽

Ioanna Pitterou ◽

Antonella Rozaria Nefeli Pontillo ◽

...

Keyword(s):

Natural Products ◽

Review Article ◽

Modified Chitosan ◽

The Past ◽

Natural Extracts ◽

Naturally Occurring ◽

Natural Polysaccharide ◽

Low Toxicity ◽

Valuable Compounds ◽

Chitosan Biopolymer

Chitosan is a cationic natural polysaccharide, which has emerged as an increasingly interesting biomaterialover the past few years. It constitutes a novel perspective in drug delivery systems and nanocarriers’ formulations due to its beneficial properties, including biocompatibility, biodegradability and low toxicity. The potentiality of chemical or enzymatic modifications of the biopolymer, as well as its complementary use with other polymers, further attract the scientific community, offering improved and combined properties in the final materials. As a result, chitosan has been extensively used as a matrix for the encapsulation of several valuable compounds. In this review article, the advantageous character of chitosan as a matrix for nanosystemsis presented, focusing on the encapsulation of natural products. A five-year literature review is attempted covering the use of chitosan and modified chitosan as matrices and coatings for the encapsulation of natural extracts, essential oils or pure naturally occurring bioactive compounds are discussed.

Download Full-text

A primer on natural product-based virtual screening

Physical Sciences Reviews ◽

10.1515/psr-2018-0105 ◽

2019 ◽

Vol 4 (6) ◽

Cited By ~ 1

Author(s):

Eleni Koulouridi ◽

Marilia Valli ◽

Fidele Ntie-Kang ◽

Vanderlan da Silva Bolzani

Keyword(s):

Natural Products ◽

Drug Discovery ◽

Molecular Modeling ◽

Virtual Screening ◽

Natural Product ◽

General Purpose ◽

Target Type ◽

Computational Techniques ◽

Specific Subset ◽

Virtual Libraries

Abstract Databases play an important role in various computational techniques, including virtual screening (VS) and molecular modeling in general. These collections of molecules can contain a large amount of information, making them suitable for several drug discovery applications. For example, vendor, bioactivity data or target type can be found when searching a database. The introduction of these data resources and their characteristics is used for the design of an experiment. The description of the construction of a database can also be a good advisor for the creation of a new one. There are free available databases and commercial virtual libraries of molecules. Furthermore, a computational chemist can find databases for a general purpose or a specific subset such as natural products (NPs). In this chapter, NP database resources are presented, along with some guidelines when preparing an NP database for drug discovery purposes.

Download Full-text

In Silico De Novo Curcuminoid Derivatives From the Compound Library of Natural Products Research Laboratories Inhibit COVID-19 3CLpro Activity

Natural Product Communications ◽

10.1177/1934578x20953262 ◽

2020 ◽

Vol 15 (9) ◽

pp. 1934578X2095326

Author(s):

Jai-Sing Yang ◽

Jo-Hua Chiang ◽

Shih‑Chang Tsai ◽

Yuan-Man Hsu ◽

Da-Tian Bau ◽

...

Keyword(s):

Natural Products ◽

Virtual Screening ◽

Binding Affinity ◽

High Throughput ◽

In Silico ◽

De Novo ◽

Compound Library ◽

Therapeutic Success ◽

High Throughput Virtual Screening

The coronavirus disease 2019 (COVID‐19) outbreak caused by the 2019 novel coronavirus (2019-nCOV) is becoming increasingly serious. In March 2019, the Food and Drug Administration (FDA) designated remdesivir for compassionate use to treat COVID-19. Thus, the development of novel antiviral agents, antibodies, and vaccines against COVID-19 is an urgent research subject. Many laboratories and research organizations are actively investing in the development of new compounds for COVID-19. Through in silico high-throughput virtual screening, we have recently identified compounds from the compound library of Natural Products Research Laboratories (NPRL) that can bind to COVID-19 3Lpro polyprotein and block COVID-19 3Lpro activity through in silico high-throughput virtual screening. Curcuminoid derivatives (including NPRL334, NPRL339, NPRL342, NPRL346, NPRL407, NPRL415, NPRL420, NPRL472, and NPRL473) display strong binding affinity to COVID-19 3Lpro polyprotein. The binding site of curcuminoid derivatives to COVID-19 3Lpro polyprotein is the same as that of the FDA-approved human immunodeficiency virus protease inhibitor (lopinavir) to COVID-19 3Lpro polyprotein. The binding affinity of curcuminoid derivatives to COVID-19 3Lpro is stronger than that of lopinavir and curcumin. Among curcuminoid derivatives, NPRL-334 revealed the strongest binding affinity to COVID-19 3Lpro polyprotein and is speculated to have an anti-COVID-19 effect. In vitro and in vivo ongoing experiments are currently underway to confirm the present findings. This study sheds light on the drug design for COVID-19 3Lpro polyprotein. Basing on lead compound development, we provide new insights on inhibiting COVID-19 attachment to cells, reducing COVID-19 infection rate and drug side effects, and increasing therapeutic success rate.

Download Full-text

Cover Picture: Inhibitors of HIV-1 Integrase-Human LEDGF/p75 Interaction Identified from Natural Products via Virtual Screening (Chin. J. Chem. 12/2012)

Chinese Journal of Chemistry ◽

10.1002/cjoc.201290035 ◽

2012 ◽

Vol 30 (12) ◽

pp. 2729-2729

Author(s):

Guoping Hu ◽

Xi Li ◽

Yaozong Li ◽

Xianqiang Sun ◽

Guixia Liu ◽

...

Keyword(s):

Natural Products ◽

Virtual Screening ◽

Hiv 1

Download Full-text

Identification of new p300 histone acetyltransferase inhibitors from natural products by a customized virtual screening method

RSC Advances ◽

10.1039/c6ra11240d ◽

2016 ◽

Vol 6 (66) ◽

pp. 61137-61140 ◽

Cited By ~ 19

Author(s):

Guo-Bo Li ◽

Lu-Yi Huang ◽

Hui Li ◽

Sen Ji ◽

Lin-Li Li ◽

...

Keyword(s):

Natural Products ◽

Virtual Screening ◽

Histone Acetyltransferase ◽

Screening Method ◽

Natural Compounds

The natural compounds NP-2, NP-3, NP-9, and NP-15 were found to be potent p300 HAT inhibitors by a customized structure-based virtual screening method.

Download Full-text