ROLE OF OMICS IN DRUG DISCOVERY FROM NATURAL SOURCES

ROLE OF OMICS IN DRUG DISCOVERY FROM NATURAL SOURCES

Nallamaddi Praneetha Reddy and P. Veeresh Babu *

Department of Pharmacology, Gokaraju Rangaraju College of Pharmacy, Bachupally, Hyderabad, Telangana, India.

ABSTRACT: The healing homes of plant life have been identified because time was immemorial. Many pathological conditions have been handled using plant-derived drug treatments. Recent advances in analytical and computational strategies have opened new avenues to technique complex natural merchandise and to use their structures to derive new and revolutionary drugs. Indeed, we're in the era of omics as applied to herbal products. Predictive computational software programs have contributed to the invention of molecular targets for natural products. The rapid adoption of omics procedures to research facts using genomics, transcriptomics, proteomics, and metabolomics has opened a new manner toward natural drug discovery. The records of omics, the technology utilized in omics gear, role of omics in natural drug discovery, its strengths and challenges of omics equipment are discussed in this review.

Keywords: Omic tools, Omic technologies, Natural drug discovery, Genome mining, DARTS, Mass spectrometry, NMR analysis

INTRODUCTION: Natural drugs consisting of plants, animals, and minerals sources had been the idea for treating human diseases. Ancient understanding has been the idea of modern medication and could remain an important supply of destiny remedy. A natural drug is a chemical compound produced using a dwelling organism observed in nature that typically has a pharmacological or biological hobby for use in pharmaceutical drug discovery and drug layout. The success of herbal drugs changed the mode of treatment ¹. Natural merchandise is extracted from various resources such as flowers, microorganisms, marine organisms, terrestrial vertebrates, and invertebrates.

Some drugs observed from plant life ‘Tiotropium bromide, Nitisinone, Galantamine hydrobromide, microorganisms ‘Micafungin sodium, Tigecycline, Everolimus, Telithromycin’, marine organisms ‘Dolabela auricularia, Squalamine’. The assets of medication had been mentioned in unique ².

Advantages of Natural Drugs:

• Treat diseases with little or no side effects.
• They have high relevance for infectious diseases.
• The higher rigidity of natural products can be valuable in drug discovery tackling protein–protein interactions.
• They are enriched with bioactive compounds with a wider area of chemical space.
• Natural products and their structural analogues have historically made a major contribution to pharmacotherapy ³.

Advantages when Compared to Synthetic Drugs: Low/Minimum cost, high potency and efficiency, enhanced tolerance, more protection, fewer side-effects, complete accessibility, recyclable ⁴.

Global Market: According to the World Health Organization (WHO) 4 billion humans, eighty percent of the sector population use herbal medicine for some components of number one health care. Also, it's expected that at least 25% of allallopathic drug treatments contain a plant derivative. The forecast is that the global market place for herbal products is predicted to be $5 Trillion with the aid of 2050. The exports of Ayurvedic and Unani medicines to different countries from India have improved from Rs. 17 crores in 1992-ninety-three to ninety-eight crores in 1998-99 ⁵.

FIG. 1: GLOBAL MARKET SHARE OF HERBAL DRUGS

Indian Trade: The annual turnover of the Indian herbal medicinal enterprise is set at Rs.2,300 crores as against the pharmaceutical industry’s turnover of Rs. 14,500 crores with a growth rate of 15 percent. The export of medicinal vegetation from India has emerged as massive in the last few years. India is the second biggest manufacturer of castor seeds in the world, generating about 1,25,000 Tonnes per annum ⁶.

OMICS: Omics is defined as the collective characterization and quantification of all the precise organic molecules, which include genes, metabolites, proteins, and RNA which can be associated with the structure, function, and dynamics of an organism or organisms. The suffix name is used for gadgets like the genome. The phrases ‘Gene’ and ‘chromosome’ were merged by Hans Winkler to describe a body of genes referred to as a genome. Omics include a mass or huge quantity of measurements according to the end point ⁷.

The suffix “omics” represents the modern technological development made in the past 3 years that permits us to concurrently examine lots of molecules. Despite the abundance and variety of the experimental and computational procedures available for omics interrogation, translating knowledge won by way of diving into varied ranges of omics into clinical practice ⁸. It is considered that there are 4 essential sorts of omics: Genomics, Transcriptomics, Proteomics, and Metabolomics. Over time other omics like Multiomics, Epigenomics, Nutrigenomics, Lipidomics, Drugomics, and so forth have been added ⁹.

History of Omics: A couple of proteins or metabolites with a practical shape were decided on and recognized in studies of the pre-omics period. After coming into the genomic generation, the gain of omics technologies is to research thousands of proteins/genes/metabolites in preference to only some. In latest years, omics technologies are used for biomarker discovery phylogenetic tree and device-wide know-how of toxicity or movement mechanism of xenobiotics, identification of signaling molecules associated with all improvement of the cell (boom, metabolism, and death) ¹⁰. A limited number of gene polymorphisms were analyzed in the pre-genomic period. One to 10 centered-orientated genes have been studied in the population. Omics has delivered new technologies and has been used inside the definition of recent generation technology. Thousands of records from special omics want to be correctly incorporated for deciphering information. Efficient integration of facts permits accurate and sturdy effects; however, omics facts are quite hard because records integration is computational. Thus, the capacity to manipulate and examine these varieties of data has ended up being an ability set. The surge in improvements of next-generation sequencing (NGS) technology and progressing enomic statistics evaluation have led to a high-throughput information era for genomes (single nucleotide polymorphisms (SNPs), and copy number editions (CNVs) ¹¹.

Sanger sequencing, also referred to as the primary generation of DNA sequencing, was invented in 1977. The period “transcriptome” appeared for the primary time in the Nineteen Nineties. Serial evaluation of gene expression (SAGE), one of the earliest sequencing-based transcriptomic tactics, was created in 1995. It employed Sanger sequencing of concatenated random transcript fragments. Ever because the first excessive-throughput era, DNA microarray, turned into established, technology to explore omics was evolved by using leaps and limits. Beyond this, omics technologies had been accelerated to research various omics at the epi-degree along with epigenome and epi transcriptome. This unexpectedly growing and ever-developing field, omics, has empowered us to uncover the problematic molecular mechanism underlying one-of-a-kind phenotypic manifestations ¹².

FIG. 2: OVERVIEW OF THE PROGRESSIVE ADVANCE IN THE METHODS TO STUDY GENES, TRANSCRIPTS AND PROTEINS IN THE INFORMATICS SCIENCES. THE ARROW REPRESENTS THE DEVELOPMENT, OVER TIME, OF THE MANY DISCIPLINES NOW INVOLVED IN BIOMEDICAL SCIENCE ACCOMPANIED BY THE FUNDAMENTAL ADVANCES IN INFORMATICS AND COMMUNITY RESOURCES. THE BROAD ROOTS OF THE OMICS REVOLUTION ARE REPRESENTED BY THE WIDER START OF THE ARROW BEFORE THE YEAR “1950”, WHEN THE FOUNDATIONS FOR A PARADIGM SHIFT IN SCIENCE.

Advantages:

• In recent years, omics technologies are used for biomarker discovery which includes new sickness biomarkers and gadget-extensive know-how of toxicity, the identity of signaling molecules associated with all improvement degrees of cellular (increase, metabolism, and demise), and early detect ion of cancer ¹³.
• Omics aids in the knowledge of biological approaches in assessment to preceding traditional strategies. It ensures extra accurate and unique diagnosis and remedies of disease through statistical analysis. Especially, it would provide an opportunity to diagnose illnesses at a very early level and take defensive measurements for toxicities because omics make clear the mechanisms underlying the toxicity, drug discovery, and development of diseases ¹⁴.
• Many factors have an impact on the nation of health and disorder, and an individual’s genetic background is an essential determinant. Examining this genetic background is, consequently, critical for identifying personal mutations that discriminate between fitness and disease. Since the elucidation of the omics facts has been generated with growing pace and efficiency, permitting the transition from research centered on man or woman genes and genetic fragments ¹⁵.

Omics Tools and Technologies: Omics technologies are aimed at primarily four omics research fields namely, genomics, transcriptomics, proteomics or metabolomics.

FIG. 3: TOOLS AND TECHNOLOGIES COMMONLY USED IN OMICS

Genomics: Genomics is the look at of organism's entire genome (WGS). In Homosapiens, the haploid genome consists of 3 billion DNA base pairs, encoding about 20,000 genes. Genomic strategies are committed to the research of interindividual variations at each germline and somatic tier through sequencing the genome of interest. The development from the DNA microarray era, first-era Sanger sequencing, the subsequent generation sequencing (NGS), and 0.33 era of lengthy reads sequencing (TGS) has enabled the sequencing of the whole genome with sufficient in-intensity to signify the mutational panorama of a given pattern ¹⁶.

Transcriptomics: The transcriptome is the total supplement of ribonucleic acid (RNA) transcripts in a cell and consists of coding (1–4% messenger) and non-coding. The analysis of mRNAs gives direct perception into the cell and tissue-precise gene expression features along with presence/absence and quantification of a transcript, assessment of opportunity splicing to expect protein isoforms, and quantitative assessment of genotype effect on gene expression the usage of expression quantitative trait loci analyses (eQTL) orallele-specific expression(ASE). Tools used are the Gene Expression Omnibus, Array Express or the Expression Atlas, or the Eukaryotic Genome database in Ensemble ¹⁷.

Proteomics: Proteomics is the study of the proteome via a combination of approaches together with proteomics, structural proteomics, and protein-protein interactions analysis.

The 4-nucleotide codes of DNA and mRNA are translated into a greater complicated code of 20 amino acids, with primary sequence polypeptides of various lengths folded into one in every of a huge variety of feasible conformations and chemical modifications ¹⁸.

Proteomics is recognized for its potential to describe cell/tissue differentiation and the discovery of diagnostic markers for disease. Eventual protein characteristic relies upon how a protein is folded. 3-d protein structures are generated via X-ray, nuclear magnetic resonance (NMR), and cryo-electron microscopy to (i) visualize protein domain names, (ii) infer molecular mechanisms and protein characteristics (iii) observe structural adjustments following ailment-related mutations and (iv) discover or increase drugs ¹⁹.

Metabolomics: Metabolites are defined as low molecular weight biomolecules (<1,500 Da) participating in cell metabolism, featuring as energy assets, signaling molecules, and metabolic intermediates with protein modulatory roles in complicated organic systems. Metabolome is known as a set of all metabolites in a cell that encompasses all biomolecules besides the genome, transcriptome, proteome, and metals.

Methods for metabolome interrogation consist of Fourier rework-infrared (FT-IR) spectroscopy, Raman spectroscopy, NMR spectroscopy, MS-based approaches inclusive of MS, MS/MS, liquid chromatography (LC)-MS) fuel chromatography (GC)-MS ²⁰.

Epigenomics: Epigenomics explains changes inside the law of gene sports without enhancing genetic sequences, which serves as a primary regulatory mechanism for gene transcription. It includes the characterization of higher-order chromatin shape and DNA/RNA adjustments inclusive of DNA/RNA methylation, Histone adjustments non-coding RNA adjustments ²¹.

Epitranscriptomics: Epitranscriptomics seeks to explain the role of RNA shape and modifications in regulating gene expression, wherein RNA modification specializes in changed nucleotides in mRNA like m6A adjustments ²².

Drugomics: Drugomics collections also are created for drugs. There are databases and meta-databases (e.g., Drug2Gene and Drug Bank) that gather drug–protein–gene interactions. These are useful to discover present drugs for a particular goal or to right away become aware of all acknowledged targets of a selected drug. An extra database, a part of the so-known Connectivity Map assignment, provides an interface to browse a group of genome-huge transcriptional profiles from cellular cultures handled with tablets. This resource is used as an excessive-throughput approach to evaluate the modulation of gene expression encouraged with the aid of positive capsules ²³.

Immunomics: The period “immunomics” was first added in 2001 and refers to the interrogation of immunology through the integration of information from genomics, proteomics, and transcriptomics, to translate molecular immunology into clinics ²⁴.

Microbiomics: Microbiomics is the technological know-how of gathering, characterizing, and quantifying molecules accountable for the shape, characteristics, and dynamics of amicrobial network with the aid of integrating omics records such as genomics, transcriptomics, proteomics, and Metabolomics ²⁵.

Role of Omics in Natural Drug Discovery: Innovative drug design from natural merchandise is wanted to fight international health challenges with brand-new technological innovation. Most important is the need for modern computational and analytical techniques for the identification of chemical components of crude plant extracts to identify compounds inflicting the preferred therapeutic effect and optimize extraction to exclude interfering components. Technological advances, which include the development of recent analytical and bioinformatic techniques, will resource the design of the latest systems, the synthesis of these new compounds, and the organic checking out of such compounds are in want for the use of omics technology for the duration of drug design and trying out to allow for the speedy manufacturing of medication from plant-primarily based natural merchandise ²⁶.

The excellent, unique identity and reliability of the plant species from which the herbal product is received could be essential for successful modern drug discovery.

FIG. 4: TECHNIQUES AVAILABLE FOR THE DISCOVERY OF NATURAL PRODUCTS

Genomics in Plant-Based Natural Products Identification and Biomarker Identification: Genomic techniques are vital in establishing an accurate identity method for plants and herbal product species. It is utilized in natural product identification, natural product, or compound concentrated on and bio-farming. Markers developed from species through genomic techniques may be included in DNA chips to offer a powerful, high-throughput device for genotyping and plant species authentication ²⁷.

Genomic Techniques Include: DNA barcoding is a mounted strategy that depends upon series variety in brief, trendy DNA areas (four hundred–800 bp) for species degree identity. DNA barcoding utilizing genomics presents a greater robust and specific identity in comparison to conventional techniques of morphological identity and local conventional names. DNA barcoding of herbal merchandise has been carried out in the authentication of herbal products.

DNA barcoding changed into utilized in a technique for the identification of plant species which includes Amaranthus hybridus L. and crude tablets ²⁸.

Genomic Mining is a method primarily based on identifying genes in all likelihood to control the biosynthesis of scaffold systems and can be used to identify natural products BGCs. Biosynthetic gene clusters (BGCs) are organized genes with unique enzymatic pastimes concerned with generating specialized metabolites. These tools for gene cluster evaluation may be applied in aggregate with spectroscopic strategies to accelerate the identification of natural merchandise and decide the stereochemistry of metabolic products. Retro biosynthesis for Targeted BGC Identification of Known Natural Products is given in ²⁹. Genome mining is a powerful device for identifying new compounds with natural resources healing houses. For instance, a new erythromycin-producing organism turned into diagnosed and remoted by using Chen et al. The usage of whole-genome sequencing and excessive-overall performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS).

Next-generation sequencing (NGS) data processing is promising for identifying therapeutically applicable viruses from an extensive range of specimen kinds. It has been installed that microorganisms may be an ability source of many natural tablets through NGS ³⁰.

Transcriptomics in Plant-Based Natural Products: Transcriptomics era ought to permit the multiplexed size of the expression of 1 to several hundred genes at a time. Only a multiplexed assay can completely enable the gene signature of multigenic diseases or purposeful responses to be used to find out broadly acting, probably extra powerful pills. The techniques concerned are RNA-Seq Technology is essential software for next-era sequencing technology (NGS). The 0.33-generation sequencing platform has found long fragment collection detection, with a much broader range of flux and detection. Using the RNA-seq to investigate the transcriptome sequencing of the organism can supplement and increase the gene database of this species, gain many expressed series tags (ESTs) facts, and discover some new useful genes, which is beneficial to the subsequent gene cloning and relevant molecular markers development ³¹.

Discovering the molecular mechanism of disorder is an essential premise for the improvement of recent target pills. Transcriptome studies can pick out the shape and characteristics of genes at the critical stage. RNA-seq is a powerful tool for detecting differentially expressed alleles of transcripts in particular biological processes and can reveal new molecular mechanisms of illnesses as no reference genome is needed. Potential drug target genes are a vital step in drug discovery. Detection of drug-brought-on genome-extensive gene expression changes can be performed by using RNA-seq. Saini et al. Screened a series of biomarkers and candidate pills associated with age-associated macular degeneration (AMD) ³². As a result, they located nicotinamide (NAM) can improve the disorder-associated phenotypes via inhibiting drusen protein, infection and supplement elements, up-regulated nucleosome, ribosome, and chromatin-editing genes through RNA-seq generation. Applications of RNA-seqare mentioned in ³³.

Gene expression microarray era (also known as Gene Chip, DNA/RNA chip, or Biochip), known as microarray, is invented in the 1990s. This technique refers back to the solving of many probe molecules (nucleic acids with known sequences) on the aid and hybridization with classified sample molecules. The number and sequence statistics of sample molecules are acquired by detecting the hybridization signal energy of each probe molecule (Gabig and Wegrzyn, 2001). The fundamental steps of a microarray experiment encompass acquiring mRNA from appropriate biological samples, labeling the RNA or cDNA copies with fluorescence, hybridizing the categorized RNA or cDNA with microarray for some time accompanied by using washing off the excess, scanning the microarray underneath a laser, and studying records by a suitable software program. Microarray detection can gain big sample records in a short time. Microarray technology makes it feasible to be widely utilized in drug screening, especially in figuring out the authenticity of conventional Chinese medicinal drug (TCM) formulae, screening of powerful elements, pharmacological mechanism studies, and chemical drug synthesis ³⁴.

Proteomics in Natural product Discovery: Proteomic tactics to innovative drug discovery from herbal products have the ability to elucidate the protein expression, protein function, metabolic and biosynthetic pathways based totally on therapeutic consequences translating to consistency in pleasant and profile of the product. The therapeutic effects of natural merchandise may be elucidated using proteomics and imaging strategies to efficiently observe the metabolism of herbal products and their compounds. Proteomics is a powerful way to clarify multi-target effects of complex herbal product arrangements in addition to the invention of more than one compound and fractions, characterization of herbal products and in the end a molecular diagnostic platform ³⁵.

As the vital issue of chemical proteomics, molecular probe draws on a linker connects lively compounds structure to the reporter institution (stationary segment medium, fluorophore, alkyne, or biotin) to form an active molecular by-product. In the target fishing manner, active compounds can bind to goal proteins and reporter group labels or improve goal proteins. After elution and digestion, proteomic strategies which include mass spectrometry or protein microarray can discover the enriched targets ³⁶. Drug Affinity Responsive Target Stability (DARTS) is one of the strategies used to perceive target proteins using label loose natural products. The principle of this system is to become aware of the modifications within the stability of an herbal product bound protein as opposed to an unbound protein whilst subjected to proteolytic remedy. This procedure has been used to validate diverse compounds, like resveratrol and rapamycin ³⁷.

Target Identification of Label-Free Natural Products: Mass spectrometry is used within the identity of sure protein. Modification of natural products, however, can result in reduced or lack of activity. These new and progressed strategies measure the responses of herbal product-goal protein complex to proteomic and thermal treatment. Using this new approach, it's far feasible to pick out several target proteins for a natural product character using proteomic analysis ³⁸.

Stability of Proteins from Costs of Oxidation (SPROX): This technique measures the irreversible oxidation of methionine residues on track proteins. A mixture of candidate drug compound and proteins is incubated with an oxidizing agent and guanidinium hydrochloride to oxidize methionine. Generated peptides are then analyzed through mass spectrometry to assess selective methionine oxidation. Analyses of oxidized and non-oxidized methionine-containing peptides versus the guanidinium hydrochloride awareness display that proteins bound to ligands display a bigger transition midpoint shift than control samples. Indeed, numerous target proteins of compounds which include resveratrol and cyclophilin A were confirmed using SPROX. This approach calls for exceptionally concentrated proteins for evaluation.

Modifications of the SPROX technique, named stable isotope labelling with amino acids in cell subculture (SILAC)-based totally SPROX is an improvement of the unique method and has the gain of overlaying more goal proteins. This technique is constrained to the most effective identifying methionine containing proteins. Other methods are mentioned in ³⁹.

Metabolomics Approaches in Natural Product Discovery: Secondary metabolites (SMs) from microbes were recognized as a prime herbal source of medications for a variety of metabolic and neurological illnesses. SMs include herbal products, such as pigments, alkaloids, poisons, and antimicrobials derived from cultivated microbes, in addition to SMs derived from non-cultivable microorganisms. However, separating SMs from various assets is a time-eating procedure. Metabolomics uses very advanced instruments to provide complete identity and structural records on the whole cell metabolome underneath designated instances.

Metabolomic profiling of natural merchandise seeks to become aware of and quantify the whole set of its feature metabolites. Metabolomic profiling of natural merchandise the usage of technologies which include extremely-overall performance high performance liquid chromatography quadruple TOF MS (UPLC–MS) has enabled identity of compounds that confer therapeutic properties on herbs including Newbouldia laevis, Cassia abbreviata, Hyptissuaveolens and Panax herbs. As a best control measure and to show consistency in species utilization, metabolomics has been used in identity of processed Panax ginseng and Panax quinquefolius using Nuclear Magnetic Resonance (NMR) based metabolomics, UPLC–QTOF MS and multivariate statistical evaluation. Metabonomics method to profiling natural merchandise for drug discovery has been hailed as a crucial phenotyping device. Enzymes or other proteins within that affected precise metabolic pathway can grow to be key to reading perturbation, which may in the end yield the discovery of novel pharmacologically essential pathways. The identity of novel drug goals is frequently followed by the discovery of novel disorder-associated metabolic changes. For example, trimethylamine (TMA) is an intestine microbial (e.g., Acinetobacter spp.) made of choline and L-carnitine metabolism, and TMA is the precursor to trimethylamine-N-oxide (TMAO) ⁴⁰.

NMR analysis of Natural Products (NP) extracts is easy and reproducible, and provides direct quantitative statistics and particular structural records, even though it has rather low sensitivity that means that it normally enables profiling best of fundamental ingredients. The programs of NMR in NP research are versatile 36 and the technique is used each at once for metabolomics of unfractionated NP extracts and for structural characterization of compounds and fractions acquired with suitable separation techniques, most customarily LC.

Dereplication of secondary metabolites in bioactive extracts includes the determination of molecular mass and formulation and pass-searching within the literature or structural NP databases with taxonomic data, which significantly assists the identity process. Such metadata, which can be tough to question within the literature, are often compiled in proprietary databases, such as the Dictionary of Natural Products. Another useful platform for metabolite identity is METLIN49, which incorporates a high-decision MS/MS database with a fragment similarity seek characteristic. This is useful for the identity of unknown compounds. To accelerate the identity of bioactive NPs in extracts, metabolomics facts may be matched to the biological sports of these extracted NP’s.

Application of liquid chromatography–high-decision mass spectrometry (LC–HRMS) metabolomics within the screening of herbal product (NP) extracts is the work of Kurita et Fifty-eight, wherein 234 bacterial extracts have been subjected to photo-primarily based phenotypic bioactivity screening and LC–HRMS metabolomics. Clustering of the ensuing statistics allowed prioritization of promising extracts for similar evaluation, resulting in the discovery of the new NPs, quinocinnolinomycins⁴⁰.

Multi-Omics-Based Natural Product Target Identification and Discovery: High-throughput omics methods such as proteomics, genomics, transcriptomics, metabolomics, and bioinformatics-based analysis can offer profound strong records and feature extraordinary capability to become aware of herbal product goals and mechanisms. A general of 359 differential proteins and a hundred and ten metabolites had been screened and specially associated with sphingolipid metabolism, supplement and coagulation cascades, glycerophospholipid metabolism, and so on.

The effective mechanism of total flavonoids extracted from Astragali radix towards cyclophosphamide-precipitated leucopenia have been proven by means of systems biology. Using metabolomics techniques, PI3K-Akt and Jak-STAT signaling pathway had been regulated via general flavonoids. Total flavonoids exhibited defensive consequences through selling cellular proliferation, modulating immunologic functions. Numerous metabolites proteins and genes have been located and regulated via BYF; capacity targets have been related to inflammatory reaction, lipid metabolism and oxidative stress. Integrating transcriptomics, proteomics, and metabolomics have been carried out to expose the impact and mechanism of Bufei Jianpi components (BJF). Long-time period anti-COPD effect targets of BJF had been detected and related to focal adhesion, antioxidant hobby and lipid metabolism ⁴¹. An incorporated evaluation of miRNAome, metabolome and proteome were performed to show the underlying efficacy mechanism of geniposide at the hepatoprotection. The extensively differentially expressed 28 miRNAs, 7 metabolites and 20 proteins have been diagnosed, respectively. Geniposide could modify citrate cycle metabolism pathways via concentrating on dehydrogenase and promoting useful recuperation. Multi-omics changed into applied to explore the pharmacological movements and healing mechanisms of Zhen-Wu-Bu-Qi Decoction that exhibited anti-inflammatory residences and guarded towards colon injury through manipulating PI3KMAPK/NF-κB signaling pathway ⁴².

FIG. 5: ROLE OF VARIOUS OMICS TECHNIQUES IN THE NATURAL DRUG DISCOVERY

Applications of Omics Tools in Drug Discovery:

Drug Safety and Toxicology: Drug side results have a vital position in drug safety. However, the conventional approach is no longer capable of confirming or clarifying the whole range of molecular responses to pills. Omics technology at the moment is well established and is considered low priced strategies. Advanced approach for drug aspect effects research is the single cellular technique, advanced to cope with cellular heterogeneity. Single mobile omics could be used to discover the complexity of individual cell behaviors underneath the same remedy situations ⁴³.

FIG. 6: STEPS INVOLVED IN THE DRUG DISCOVERY BY OMICS

Drug Targets: A drug goal can be defined as a molecule in the frame, typically a protein, that is intrinsically associated with a selected disorder process and that could be addressed by using a drug to produce a desired healing. Drug objectives must showcase the following numerous basic capabilities: involvement in a crucial biological pathway; functionally and structurally characterized; and druggable (able to bind to small molecules, implying the presence of a binding website). Traditionally, structure-based evaluation has been used to look for suitable drug objectives, which results in the concept of ‘druggability’. A drug goal indeed is regularly defined as proteins that own protein folds that choose interactions with drug-like chemical substances. Many proteins are druggable consistent with their structure; however, their binding will no longer lead to therapeutic benefit ⁴⁴.

Strengths and Challenges of Omic Tools:

Strengths:

• Sequencing-based totally technologies, that are the maximum superior of the omics technologies in terms of availability of laboratory reagents for standardized protocols, analytical equipment and public databases for statistics sharing, provide specific opportunities to acquire high great from small amounts of tissues or individual cells to cope with a huge variety of organic questions.
• Developments in MS have dramatically extended sensitivity while reducing the quantity of sample required for excessive-throughput analyses and now allow for the detection of minimal variations in protein abundances, identification of submit-translational modifications and different applications from an extensive variety of samples and tissues.
• Depending on the application and instrumentation, metabolomics captures small molecule records in strong (i.e., stable-nation NMR), liquid ((liquid chromatography MS (LC-MS), capillary electrophoresis MS (CE-MS)) or fuel section (gasoline chromatography MS (GC-MS)) the usage of spectroscopy (i.e., NMR) and MS.
• Proteomics is advancing our know-how in drug discovery, such as diagnosis, protein-based biomarker development and therapeutics.
• The visualization of omics data the use of information from microarrays, RNA deep sequencing, mass spectrometry (MS), nuclear magnetic resonance (NMR) and protein interactions, large development has been made to develop extra tools and approaches for incorporated omics evaluation ⁴⁴.

Challenges: (i) Experimental challenges, (ii) Individual omics datasets, (iii) Integration issues, (iv) Data issues and (v) Biological knowledge ⁴⁵.

FIG. 7: CHALLENGES OF OMICS

CONCLUSION: Access to big-scale omics datasets (genomics, transcriptomics, proteomics, metabolomics, metagenomics, phenomics, etc.) has revolutionized biology and caused the emergence of structures techniques to strengthen our expertise of organic strategies, drug discovery, drug goal discovery, drug discovery from natural merchandise. By lowering time and value to generate these datasets, omics information integration has created interesting possibilities and big demanding situations. Discovering natural product goals and characterizing their interactions with target protein are crucial to recognize each of their mechanism of action, therapeutic results, and capability facet results and toxicities. Here in, multi-omics strategies are held up to demonstrate the utility of combined genomics, proteomics, metabolomics, and bioinformatics techniques in target identity.

ACKNOWLEDGEMENTS: Authors are grateful to the Principal and Management of Gokaraju Rangaraju College of Pharmacy for their encouragement and providing all the facilities required in collecting the literature and preparing this manuscript.

CONFLICTS OF INTEREST: Both the authors have no conflicts of interest to declare.

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    How to cite this article:

    Reddy NP and Babu PV: Role of omics in drug discovery from natural sources. Int J Pharm Sci & Res 2024; 15(2): 290-01. doi: 10.13040/IJPSR.0975-8232.15(2).290-01.

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