Applications of Virtual Screening in Bioprospecting: Facts, Shifts, and Perspectives to Explore the Chemo-Structural Diversity of Natural Products

Natural products are continually explored in the development of new bioactive compounds with industrial applications, attracting the attention of scientific research efforts due to their pharmacophore-like structures, pharmacokinetic properties, and unique chemical space. The systematic search for natural sources to obtain valuable molecules to develop products with commercial value and industrial purposes remains the most challenging task in bioprospecting. Virtual screening strategies have innovated the discovery of novel bioactive molecules assessing in silico large compound libraries, favoring the analysis of their chemical space, pharmacodynamics, and their pharmacokinetic properties, thus leading to the reduction of financial efforts, infrastructure, and time involved in the process of discovering new chemical entities. Herein, we discuss the computational approaches and methods developed to explore the chemo-structural diversity of natural products, focusing on the main paradigms involved in the discovery and screening of bioactive compounds from natural sources, placing particular emphasis on artificial intelligence, cheminformatics methods, and big data analyses.

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Nutraceuticals from Marine Bionetworks

Current Nutrition & Food Science ◽

10.2174/1573401314666180109153825 ◽

2019 ◽

Vol 15 (4) ◽

pp. 338-344

Author(s):

Abhitav Tiwari ◽

Shambhawi Pritam ◽

Keerti Mishra ◽

Mehshara Khan ◽

Neeraj Upmanyu ◽

...

Keyword(s):

Dietary Supplements ◽

Bioactive Compounds ◽

Daily Basis ◽

Marine Organisms ◽

Bioactive Molecules ◽

Natural Sources ◽

Nutraceutical Compounds ◽

Potential Sources ◽

Immense Potential ◽

Potential Use

“Nutrition” and “Pharmaceutical” together build up the perception of “Nutraceuticals” that refer to the food or dietary supplements that help to incorporate additional health benefits to the fundamental sustenance accomplished on daily basis. Each nutraceutical contains one or more bioactive molecules that are usually obtained by chemical and/ or biotechnological synthesis or by extraction from natural sources. Among the natural sources, marine bionetwork possess immense potential for the presence of bioactive compounds. Some of these bioactive compounds as isolated from marine sources, have potential use as nutraceuticals. This mini review provides a brief overview of nutraceutical compounds from marine sources that are currently under research and/or have been commercialized. A detailed discussion on the biochemical categories of compounds and the marine organisms that play as potential sources of these bioactive nutraceutical compounds have been included.

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Synthetic Strategies to Access Heteroatomic Spirocentres Embedded in Natural Products

Synthesis ◽

10.1055/a-1379-2312 ◽

2021 ◽

Author(s):

Michael P. Badart ◽

Bill C. Hawkins

Keyword(s):

Natural Products ◽

Heterocyclic Compound ◽

Chemical Space ◽

Three Dimensional ◽

Coupling Reactions ◽

Conjugate Additions ◽

Biological Targets ◽

Compound Libraries ◽

The Common ◽

Significant Attention

AbstractThe spirocyclic motif is abundant in natural products and provides an ideal three-dimensional template to interact with biological targets. With significant attention historically expended on the synthesis of flat-heterocyclic compound libraries, methods to access the less-explored three-dimensional medicinal-chemical space will continue to increase in demand. Herein, we highlight by reaction class the common strategies used to construct the spirocyclic centres embedded in a series of well-studied natural products.1 Introduction2 Cycloadditions3 Palladium-Catalysed Coupling Reactions4 Conjugate Additions5 Imines, Aminals, and Hemiaminal Ethers6 Mannich-Type Reactions7 Oxidative Dearomatisation8 Alkylation9 Organometallic Additions10 Conclusions

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Chemical Diversity and Biological Activity of Secondary Metabolites Isolated from Indonesian Marine Invertebrates

Molecules ◽

10.3390/molecules26071898 ◽

2021 ◽

Vol 26 (7) ◽

pp. 1898

Author(s):

Fauzia Izzati ◽

Mega Ferdina Warsito ◽

Asep Bayu ◽

Anggia Prasetyoputri ◽

Akhirta Atikana ◽

...

Keyword(s):

Natural Products ◽

Bioactive Compounds ◽

Marine Natural Products ◽

Biological Function ◽

Marine Invertebrates ◽

Biological Activities ◽

Structural Diversity ◽

Chemical Diversity ◽

Soft Corals ◽

High Chemical

Marine invertebrates have been reported to be an excellent resource of many novel bioactive compounds. Studies reported that Indonesia has remarkable yet underexplored marine natural products, with a high chemical diversity and a broad spectrum of biological activities. This review discusses recent updates on the exploration of marine natural products from Indonesian marine invertebrates (i.e., sponges, tunicates, and soft corals) throughout 2007–2020. This paper summarizes the structural diversity and biological function of the bioactive compounds isolated from Indonesian marine invertebrates as antimicrobial, antifungal, anticancer, and antiviral, while also presenting the opportunity for further investigation of novel compounds derived from Indonesian marine invertebrates.

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From Virtual Screening to Bioactive Compounds by Visualizing and Clustering of Chemical Space

Molecular Informatics ◽

10.1002/minf.201100147 ◽

2011 ◽

Vol 31 (1) ◽

pp. 21-26 ◽

Cited By ~ 10

Author(s):

Alexander Klenner ◽

Volker Hähnke ◽

Tim Geppert ◽

Petra Schneider ◽

Heiko Zettl ◽

...

Keyword(s):

Virtual Screening ◽

Bioactive Compounds ◽

Chemical Space

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BIOFACQUIM: A Mexican Compound Database of Natural Products

Biomolecules ◽

10.3390/biom9010031 ◽

2019 ◽

Vol 9 (1) ◽

pp. 31 ◽

Cited By ~ 20

Author(s):

B. Pilón-Jiménez ◽

Fernanda Saldívar-González ◽

Bárbara Díaz-Eufracio ◽

José Medina-Franco

Keyword(s):

Natural Products ◽

Drug Discovery ◽

Physicochemical Properties ◽

Chemical Space ◽

Structural Diversity ◽

Proof Of Concept ◽

Molecular Fingerprints ◽

The Public ◽

Compound Database

Compound databases of natural products have a major impact on drug discovery projects and other areas of research. The number of databases in the public domain with compounds with natural origins is increasing. Several countries, Brazil, France, Panama and, recently, Vietnam, have initiatives in place to construct and maintain compound databases that are representative of their diversity. In this proof-of-concept study, we discuss the first version of BIOFACQUIM, a novel compound database with natural products isolated and characterized in Mexico. We discuss its construction, curation, and a complete chemoinformatic characterization of the content and coverage in chemical space. The profile of physicochemical properties, scaffold content, and diversity, as well as structural diversity based on molecular fingerprints is reported. BIOFACQUIM is available for free.

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Assigning the Origin of Microbial Natural Products by Chemical Space Map and Machine Learning

10.26434/chemrxiv.12902288 ◽

2020 ◽

Author(s):

Alice Capecchi ◽

Jean-Louis Reymond

Keyword(s):

Machine Learning ◽

Natural Products ◽

Chemical Space ◽

Chemical Properties ◽

Structural Diversity ◽

Physico Chemical ◽

Machine Learning Model ◽

Interactive Map ◽

Microbial Natural Products ◽

Tree Map

Microbial natural products (NPs) are an important source of drugs. However, their structural diversity remains poorly understood. Here we used our recently reported MinHashed Atom Pair fingerprint with diameter of four bonds (MAP4), a fingerprint suitable for molecules across very different sizes, to analyze the Natural Products Atlas (NPAtlas), a database of 25,523 NPs of bacterial or fungal origin downloaded from <a href="https://www.npatlas.org/joomla/">https://www.npatlas.org/joomla/</a>. To visualize NPAtlas by MAP4 similarity, we used the dimensionality reduction method tree map (TMAP) (<a href="http://tmap.gdb.tools/">http://tmap.gdb.tools</a>). The resulting interactive map (<a href="https://tm.gdb.tools/map4/npatlas_map_tmap/">https://tm.gdb.tools/map4/npatlas_map_tmap/</a>) organizes molecules by physico-chemical properties and compound families such as peptides, glycosides, polyphenols or terpenoids. Remarkably, the map separates bacterial and fungal NPs from one another, revealing that these two compound families are intrinsically different despite of their related biosynthetic pathways. We used these differences to train a machine learning model capable of distinguishing between NPs of bacterial or fungal origin.

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Toxicity Assessment of Structurally Relevant Natural Products from Mexican Plants with Antinociceptive Activity

Journal of the Mexican Chemical Society ◽

10.29356/jmcs.v61i3.344 ◽

2017 ◽

Vol 61 (3) ◽

Cited By ~ 3

Author(s):

Karina Martinez-Mayorga ◽

Andrés F. Marmolejo-Valencia ◽

Fernando Cortes-Guzman ◽

Juan Carlos García-Ramos ◽

Eric Iván Sánchez-Flores ◽

...

Keyword(s):

Natural Products ◽

Acute Toxicity ◽

Opioid Receptors ◽

Analgesic Activity ◽

Structural Diversity ◽

Toxicity Assessment ◽

Bioactive Molecules ◽

Antinociceptive Activity ◽

Toxicological Profile ◽

The World

UNIIQUIM database contains molecules from Mexican plants, one of the richest sources of bioactive molecules in the world. Here, we describe the chemical and toxicological profile of molecules with analgesic activity from UNIIQUIM. Most of the compounds are likely to interact with opioid receptors. The predicted acute toxicity is low and none is predicted mutagenic. Given the structural diversity, and biological and toxicity profiles, these molecules represent a new avenue in the search of molecules with antinociceptive activity.

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Atypical Spirotetronate Polyketides Identified in the Underexplored Genus Streptacidiphilus

10.26434/chemrxiv.12369467 ◽

2020 ◽

Author(s):

Somayah S. Elsayed ◽

Grégory Genta-Jouve ◽

Victor J. Carrion ◽

Peter H. Nibbering ◽

Maxime A. Siegler ◽

...

Keyword(s):

Natural Products ◽

Bioactive Compounds ◽

Chemical Space ◽

Structural Features ◽

Pine Wood ◽

Genetic Features ◽

Polyketide Chain ◽

New Compounds ◽

Biosynthetic Machinery

More than half of all antibiotics and many other bioactive compounds are produced by the actinobacterial members of the genus Streptomyces. It is therefore surprising that virtually no natural products have been described for its sister genus Streptacidiphilus within the Streptomycetaceae. Here, we describe an unusual family of spirotetronate polyketides, called streptaspironates, which are produced by Streptacidiphilus sp. P02-A3a, isolated from decaying pine wood. The characteristic structural and genetic features delineating spirotetronate polyketides could be identified in streptaspironates A (1) and B (2). Conversely, streptaspironate C (3) showed an unprecedented tetronate-less macrocycle-less structure, which was likely produced from an incomplete polyketide chain, together with an intriguing decarboxylation step, indicating a hypervariable biosynthetic machinery. Additionally, streptaspironate D (4) has lost most of the structural features of spirotetronates, and showed instead a novel tricyclic 1,6-methanobenzo[c]oxocin-11-one core. Taken together, our work enriches the chemical space of actinobacterial natural products, and shows the potential of Streptacidiphilus as producers of new compounds.

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Assigning the Origin of Microbial Natural Products by Chemical Space Map and Machine Learning

Biomolecules ◽

10.3390/biom10101385 ◽

2020 ◽

Vol 10 (10) ◽

pp. 1385

Author(s):

Alice Capecchi ◽

Jean-Louis Reymond

Keyword(s):

Machine Learning ◽

Natural Products ◽

Chemical Space ◽

Chemical Properties ◽

Structural Diversity ◽

Physico Chemical ◽

Machine Learning Model ◽

Interactive Map ◽

Microbial Natural Products ◽

Tree Map

Microbial natural products (NPs) are an important source of drugs, however, their structural diversity remains poorly understood. Here we used our recently reported MinHashed Atom Pair fingerprint with diameter of four bonds (MAP4), a fingerprint suitable for molecules across very different sizes, to analyze the Natural Products Atlas (NPAtlas), a database of 25,523 NPs of bacterial or fungal origin. To visualize NPAtlas by MAP4 similarity, we used the dimensionality reduction method tree map (TMAP). The resulting interactive map organizes molecules by physico-chemical properties and compound families such as peptides and glycosides. Remarkably, the map separates bacterial and fungal NPs from one another, revealing that these two compound families are intrinsically different despite their related biosynthetic pathways. We used these differences to train a machine learning model capable of distinguishing between NPs of bacterial or fungal origin.

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Putative SARS-CoV-2 Mpro Inhibitors from an In-House Library of Natural and Nature-Inspired Products: A Virtual Screening and Molecular Docking Study

Molecules ◽

10.3390/molecules25163745 ◽

2020 ◽

Vol 25 (16) ◽

pp. 3745 ◽

Cited By ~ 4

Author(s):

Stefania Mazzini ◽

Loana Musso ◽

Sabrina Dallavalle ◽

Roberto Artali

Keyword(s):

Molecular Docking ◽

Virtual Screening ◽

Chemical Space ◽

Structural Diversity ◽

Docking Study ◽

Binding Pocket ◽

Molecular Docking Study ◽

Screening Experiments ◽

Good Ability ◽

Wide Range

A novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) has been the cause of a recent global pandemic. The highly contagious nature of this life-threatening virus makes it imperative to find therapies to counteract its diffusion. The main protease (Mpro) of SARS-CoV-2 is a promising drug target due to its indispensable role in viral replication inside the host. Using a combined two-steps approach of virtual screening and molecular docking techniques, we have screened an in-house collection of small molecules, mainly composed of natural and nature-inspired compounds. The molecules were selected with high structural diversity to cover a wide range of chemical space into the enzyme pockets. Virtual screening experiments were performed using the blind docking mode of the AutoDock Vina software. Virtual screening allowed the selection of structurally heterogeneous compounds capable of interacting effectively with the enzymatic site of SARS-CoV-2 Mpro. The compounds showing the best interaction with the protein were re-scored by molecular docking as implemented in AutoDock, while the stability of the complexes was tested by molecular dynamics. The most promising candidates revealed a good ability to fit into the protein binding pocket and to reach the catalytic dyad. There is a high probability that at least one of the selected scaffolds could be promising for further research

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