Exploring the molecular interaction of pheniramine with Enterococcus faecalis homoserine kinase: In-silico studies.

Infections caused by the bacteria Enterococcus faecalis (also known as E. faecalis) are common in hospitals. This bacterium is resistant to a wide range of medicines and causes a variety of nosocomial infections. An increase in the number of infections caused by multidrug-resistant (MDR) bacteria is causing substantial economic and health issues around the world. Consequently, new therapeutic techniques to tackle the growing threat of E. faecalis infections must be developed as soon as possible. In this regard, we have targeted a protein that is regarded to be critical for the survival of bacteria in this experiment. Homoserine kinase (HSK) is a threonine metabolism enzyme that belongs to the GHMP kinase superfamily. It is a crucial enzyme in threonine metabolism. This enzyme is responsible for a critical step in the threonine biosynthesis pathway. Given the important function that E. faecalis Homoserine Kinase (ESK) plays in bacterial metabolism, we report here cloning, expression, purification and structural studies of E. faecalis HSK using homology modelling. In addition, we have reported on the model's molecular docking and Molecular Dynamic Stimulation (MD Stimulation) investigations to validate the results of the docking experiments. The results were promising. In silico investigations came up with the conclusion: pheniramine has good binding affinity for the E. faecalis HSK.

The potential application of genome editing by using CRISPR/Cas9, and its engineered and ortholog variants for studying the transcription factors involved in the maintenance of phosphate homeostasis in model plants.

Phosphorus (P), an essential macronutrient, is pivotal for growth and development of plants. Availability of phosphate (Pi), the only assimilable P, is often suboptimal in rhizospheres. Pi deficiency triggers an array of spatiotemporal adaptive responses including the differential regulation of several transcription factors (TFs). Studies on MYB TF PHR1 in Arabidopsis thaliana (Arabidopsis) and its orthologs OsPHRs in Oryza sativa (rice) have provided empirical evidence of their significant roles in the maintenance of Pi homeostasis. Since the functional characterization of PHR1 in 2001, several other TFs have now been identified in these model plants. This raised a pertinent question whether there are any likely interactions across these TFs. Clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) system has provided an attractive paradigm for editing genome in plants. Here, we review the applications and challenges of this technique for genome editing of the TFs for deciphering the function and plausible interactions across them. This technology could thus provide a much-needed fillip towards engineering TFs for generating Pi use efficient plants for sustainable agriculture. Furthermore, we contemplate whether this technology could be a viable alternative to the controversial genetically modified (GM) rice or it may also eventually embroil into a limbo.

Exploring insights of syntaxin superfamily proteins from Entamoeba histolytica: a prospective simulation, protein-protein interaction, and docking study.

Entamoeba histolytica (Eh), a parasitic protozoan and the causative agent of invasive Amoebiasis, invade the host tissue through an effective secretory pathway. There are several lines of evidence suggesting that amoebic trophozoite pore-forming complex amoebapore and a large class of proteases enzymes including rhomboid proteases, cysteine proteases, and metalloproteases are implicated in host tissue invasion. For successful delivery of these molecules/cargos, trophozoites heavily rely on sorting machinery from the endoplasmic reticulum, Golgi to plasma membrane. Although, sole secretion machinery in E. histolytica is not characterized yet. Therefore, here our aim is to understand the properties of key molecules N-ethylmaleimide-sensitive fusion protein attached to protein receptors (SNAREs) in E. histolytica. SNAREs proteins are an important component of the membrane-trafficking machinery and have been associated in a range of processes including vesicle tethering, fusion as well as specificity of vesicular transport in all eukaryotic cells. SNARE proteins are architecturally simple, categorized by the presence of one copy of a homologous coiled-coil forming motif. However, the structural information and protein-protein interaction study of Eh-associated syntaxin proteins are still not known. Here, we characterize the syntaxin 1 like molecule and VAMP from Eh through physiochemical profiling, modeling, atomistic simulation, protein-protein interaction, and docking approaches on the proteins containing SNARE and synaptobrevin domain. The modeled structures and the critical residues recognized through protein interaction and docking study may provide better structural and functional insights into these proteins and may aid in the development of newer diagnostic assays.

In silico prediction, molecular docking and binding studies of acetaminophen and dexamethasone to Enterococcus faecalis diaminopimelate epimerase.

Enterococcus faecalis (E. faecalis) is a Gram-positive coccoid, non-sporulating, facultative anaerobic, multidrug resistance bacterium responsible for almost 65% to 80% of all enterococcal nosocomial infections. It usually causes infective endocarditis, urinary tract and surgical wound infections. The increase in E. faecalis resistance to conventionally available antibiotic has rekindled intense interest in developing useful antibacterial drugs. In E. faecalis, diaminopimelate epimerase (DapF) is involved in the lysine biosynthetic pathway. The product of this pathway is precursors of peptidoglycan synthesis, which is a component of bacterial cell wall. Also, because mammals lack this enzyme, consequently E. faecalis diaminopimelate epimerase (EfDapF) represents a potential target for developing novel class of antibiotics. In this regard, we have successfully cloned, overexpressed the gene encoding DapF in BL-21(DE3) and purified with Ni-NTA Agarose resin. In addition to this, binding studies were performed using fluorescence spectroscopy in order to confirm the bindings of the identified lead compounds (acetaminophen and dexamethasone) with EfDapF. Docking studies revealed that acetaminophen found to make hydrogen bonds with Asn72 and Asn13 while dexamethasone interacted by forming hydrogen bonds with Asn205 and Glu223. Thus, biochemical studies indicated acetaminophen and dexamethasone, as potential inhibitors of EfDapF and eventually can reduce the catalytic activity of EfDapF.

Valorization of Dairy Wastes: Integrative Approaches for Value Added Products.

The era of rapid industrialization succeeded by a shift in organizational focus on research and technology development which has fueled many industries along with the dairy industry to grow at an exponential rate. The dairy industry has achieved remarkable growth in the last decade in India. Waste produced by dairy industry consists of a high organic load thus cannot be discharged untreated. Even though treatment and management of waste are well documented, but the main problem is concerned with sludge produced after treatment. There is a gap in the application of various methods for effective treatment of the waste, hence there is a need for technology-oriented research in this area because of a paradigm shift in perspectives towards sustainable management of waste to recover value added products including energy as energy demand is also rising. Sludge which is generally land spread can also be used for energy generation. This paper discusses the environmental effects of waste generated due to dairy industrial activities; various methods used for the advanced treatment of dairy waste. This review article aims to present and discuss the state-of-art information for recovery of value-added products (single cell protein, biofertilizers, biopolymers and biosurfactants) from dairy waste with emphasis on integration of technologies for environmental sustainability. This paper also includes challenges and future perspectives in this field.

A comparative in silico analysis of Rab5 proteins from pathogenic species to find its role in the pathogenesis.

The enteric protozoan parasite, Entamoeba histolytica (Eh), is the causative agent of amoebic dysentery and liver abscess in humans. It infects around 50 million people worldwide, which is a third general cause of death from parasitic diseases after malaria and schistosomiasis. The other prevalent form of the disease is Visceral leishmaniasis caused by Leishmania donovani which is a human blood parasite. On the other hand, the Toxoplasma gondii is an obligate intracellular protozoan parasite; it causes serious opportunistic infections in HIV-positive persons. The biological processes in all living organisms are mostly mediated by the proteins, and recognizing new target proteins and finding their function in pathogenesis will help in choosing better diagnostic markers. In eukaryotes, Rab protein plays a major role in pathogenesis. Rabs represent the largest branch in the Ras superfamily of GTPases. Among them, the Rab5 is important in the endocytosis and thus involved in pathogenesis. In this paper, we discussed the physiochemical profiling, modelling, and docking of the Rab5 protein from pathogenic species that is Entamoeba histolytica, Leishmania donovani, and Toxoplasma gondii. The modeled structures from this study and the key residues identified would give a better understanding of the three-dimensional structure and functional insights into these proteins and help in developing new drug targets.

Identification and evaluation of quercetin as a potential inhibitor of naphthoate synthase from Enterococcus faecalis.

Enterococcus faecalis is a gram-positive, rod-shape bacteria responsible for around 65% to 80% of all enterococcal nosocomial infections. It is multidrug resistant (MDR) bacterium resistant to most of the first-line antibiotics. Due to the emergence of MDR strains, there is an urgent need to find novel targets to develop new antibacterial drugs against E. faecalis. In this regard, we have identified naphthoate synthase (1,4-dihydroxy-2-naphthoyl-CoA synthase, EC: 4.1.3.36; DHNS) as an anti-E. faecalis target, as it is an essential enzyme for menaquinone (vitamin K2 ) synthetic pathway in the bacterium. Thus, inhibiting naphtholate synthase may consequently inhibit the bacteria's growth. In this regard, we report here cloning, expression, purification, and preliminary structural studies of naphthoate synthase along with in silico modeling, molecular dynamic simulation of the model and docking studies of naphthoate synthase with quercetin, a plant alkaloid. Biochemical studies have indicated quercetin, a plant flavonoid as the potential lead compound to inhibit catalytic activity of EfDHNS. Quercetin binding has also been validated by spectrofluorimetric studies in order to confirm the bindings of the ligand compound with EfDHNS at ultralow concentrations. Reported studies may provide a base for structure-based drug development of antimicrobial compounds against E. faecalis.

Structural and thermodynamic characterization of metal binding in Vps29 from Entamoeba histolytica: implication in retromer function.

Vps29 is the smallest subunit of retromer complex with metallo-phosphatase fold. Although the role of metal in Vps29 is in quest, its metal binding mutants has been reported to affect the localization of the retromer complex in human cells. In this study, we report the structural and thermodynamic consequences of these mutations in Vps29 from the protozoan parasite, Entamoeba histolytica (EhVps29). EhVps29 is a zinc binding protein as revealed by X-ray crystallography and isothermal titration calorimetry. The metal binding pocket of EhVps29 exhibits marked differences in its 3-dimensional architecture and metal coordination in comparison to its human homologs and other metallo-phosphatases. Alanine substitutions of the metal-coordinating residues showed significant alteration in the binding affinity of EhVps29 for zinc. We also determined the crystal structures of metal binding defective mutants (D62A and D62A/H86A) of EhVps29. Based on our results, we propose that the metal atoms or the bound water molecules in the metal binding site are important for maintaining the structural integrity of the protein. Further cellular studies in the amoebic trophozoites showed that the overexpression of wild type EhVps29 leads to reduction in intracellular cysteine protease activity suggesting its crucial role in secretion of the proteases.

Structure of Leishmania donovani coronin coiled coil domain reveals an antiparallel 4 helix bundle with inherent asymmetry.

Coiled coils are ubiquitous structural motifs that serve as a platform for protein-protein interactions and play a central role in myriad physiological processes. Though the formation of a coiled coil requires only the presence of suitably spaced hydrophobic residues, sequence specificities have also been associated with specific oligomeric states. RhXXhE is one such sequence motif, associated with parallel trimers, found in coronins and other proteins. Coronin, present in all eukaryotes, is an actin-associated protein involved in regulating actin turnover. Most eukaryotic coronins possess the RhXXhE trimerization motif. However, a unique feature of parasitic kinetoplastid coronin is that the positions of R and E are swapped within their coiled coil domain, but were still expected to form trimers. To understand the role of swapped motif in oligomeric specificity, we determined the X-ray crystal structure of Leishmania donovani coronin coiled coil domain (LdCoroCC) at 2.2Å, which surprisingly, reveals an anti-parallel tetramer assembly. Small angle X-ray scattering studies and chemical crosslinking confirm the tetramer in solution and is consistent with the oligomerization observed in the full length protein. Structural analyses reveal that LdCoroCC possesses an inherent asymmetry, in that one of the helices of the bundle is axially shifted with respect to the other three. The analysis also identifies steric reasons that cause this asymmetry. The bundle adapts an extended a-d-e core packing, the e residue being polar (with an exception) which results in a thermostable bundle with polar and apolar interfaces, unlike the existing a-d-e core antiparallel homotetramers with apolar core. Functional implications of the anti-parallel association in kinetoplastids are discussed.

Novel protein-protein interaction between spermidine synthase and S-adenosylmethionine decarboxylase from Leishmania donovani.

Polyamine biosynthesis pathway has long been considered an essential drug target for trypanosomatids including Leishmania. S-adenosylmethionine decarboxylase (AdoMetDc) and spermidine synthase (SpdSyn) are enzymes of this pathway that catalyze successive steps, with the product of the former, decarboxylated S-adenosylmethionine (dcSAM), acting as an aminopropyl donor for the latter enzyme. Here we have explored the possibility of and identified the protein-protein interaction between SpdSyn and AdoMetDc. The protein-protein interaction has been identified using GST pull down assay. Isothermal titration calorimetry reveals that the interaction is thermodynamically favorable. Fluorescence spectroscopy studies also confirms the interaction, with SpdSyn exhibiting a change in tertiary structure with increasing concentrations of AdoMetDc. Size exclusion chromatography suggests the presence of the complex as a hetero-oligomer. Taken together, these results suggest that the enzymes indeed form a heteromer. Computational analyses suggest that this complex differs significantly from the corresponding human complex, implying that this complex could be a better therapeutic target than the individual enzymes.

Insights into the GTP/GDP cycle of RabX3, a novel GTPase from Entamoeba histolytica with tandem G-domains.

Members of the small GTPase Ras superfamily regulate a host of systems through their ability to catalyze the GTP/GDP cycle. All family members reported thus far possess a single GTPase domain with a P-loop containing a nucleoside triphosphate hydrolase fold. Here for the first time we report a novel member from Entamoeba histolytica, EhRabX3, which harbors two GTPase domains in tandem and exhibits unique biochemical properties. A combination of biochemical and microcalorimetric studies revealed that EhRabX3 binds to a single guanine nucleotide through its N-terminal domain. Unlike most of the members of the Ras superfamily, the dissociation of the nucleotide from EhRabX3 is independent of Mg(2+), perhaps indicating a novel mechanism of nucleotide exchange by this protein. We found that EhRabX3 is extremely sluggish in hydrolyzing GTP, and that could be attributed to its atypical nucleotide binding pocket. It harbors substitutions at two positions that confer oncogenicity to Ras because of impaired GTP hydrolysis. Engineering these residues into the conserved counterparts enhanced their GTPase activity by at least 20-fold. In contrast to most of the members of the Ras superfamily, EhRabX3 lacks the prenylation motif. Using indirect immunofluorescence and biochemical fractionation, we demonstrated that the protein is distributed all over the cytosol in amoebic trophozoites. Collectively, this unique ancient GTPase exhibits a striking evolutionary divergence from the other members of the superfamily.

Free Radicals, Mitochondrial Dysfunction and Sepsis-induced Organ Dysfunction: A Mechanistic Insight.

Sepsis is a complex clinical condition and a leading cause of death worldwide. During Sepsis, there is a derailment in the host response to infection, which can progress to severe sepsis and multiple organ dysfunction or failure, which leads to death. Free radicals, including reactive oxygen species (ROS) generated predominantly in mitochondria, are one of the key players in impairing normal organ function in sepsis. ROS contributing to oxidative stress has been reported to be the main culprit in the injury of the lung, heart, liver, kidney, gastrointestinal, and other organs. Here in the present review, we describe the generation, and essential properties of various types of ROS, their effect on macromolecules, and their role in mitochondrial dysfunction. Furthermore, the mechanism involved in the ROS-mediated pathogenesis of sepsis-induced organ dysfunction has also been discussed.

Cloning, overexpression, purification and crystallization of the CRN12 coiled-coil domain from Leishmania donovani.

Leishmania donovani coronin CRN12 is an actin-binding protein which consists of two domains: an N-terminal WD repeat domain and a C-terminal coiled-coil domain. The coiled-coil domain is 53 residues in length. Helix-helix interactions in general and coiled coils in particular are ubiquitous in the structure of proteins and play a significant role in the association among proteins, including supramolecular assemblies and transmembrane receptors that mediate cellular signalling, transport and actin dynamics. The L. donovani coronin CRN12 coiled-coil domain (5.8 kDa) was cloned, overexpressed, purified to homogeneity and the N-terminal 6×His tag was successfully removed by thrombin cleavage. Crystals of recombinant L. donovani coronin CRN12 coiled-coil domain were grown by vapour diffusion using a hanging-drop setup. Diffraction-quality crystals were obtained and data extending to 2.46 Šresolution were collected at 100 K on BM14, ESRF, Grenoble, France. The crystal belonged to the monoclinic space group C2, with unit-cell parameters a = 118.0, b = 50.6, c = 46.0 Å, ß = 111.0°. Matthews coefficient (VM) calculations suggested the presence of 4-6 molecules in the asymmetric unit, corresponding to a solvent content of ∼33-55%, and are consistent with self-rotation function calculations.

Fast Track Diagnostic Tools for Clinical Management of Sepsis: Paradigm Shift from Conventional to Advanced Methods.

Sepsis is one of the deadliest disorders in the new century due to specific limitations in early and differential diagnosis. Moreover, antimicrobial resistance (AMR) is becoming the dominant threat to human health globally. The only way to encounter the spread and emergence of AMR is through the active detection and identification of the pathogen along with the quantification of resistance. For better management of such disease, there is an essential requirement to approach many suitable diagnostic techniques for the proper administration of antibiotics and elimination of these infectious diseases. The current method employed for the diagnosis of sepsis relies on the conventional culture of blood suspected infection. However, this method is more time consuming and generates results that are false negative in the case of antibiotic pretreated samples as well as slow-growing microbes. In comparison to the conventional method, modern methods are capable of analyzing blood samples, obtaining accurate results from the suspicious patient of sepsis, and giving all the necessary information to identify the pathogens as well as AMR in a short period. The present review is intended to highlight the culture shift from conventional to modern and advanced technologies including their limitations for the proper and prompt diagnosing of bloodstream infections and AMR detection.

Hydrogen Production from Gadolinium-Promoted Yttrium-Zirconium-Supported Ni Catalysts through Dry Methane Reforming.

Hydrogen production from dry reforming of methane (DRM) not only concerns with green energy but also involves the consumption of two greenhouse gases CH4 and CO2. The lattice oxygen endowing capacity, thermostability, and efficient anchoring of Ni has brought the attention of the DRM community over the yttria-zirconia-supported Ni system (Ni/Y + Zr). Herein, Gd-promoted Ni/Y + Zr is characterized and investigated for hydrogen production through DRM. The H2-TPR → CO2-TPD → H2-TPR cyclic experiment indicates that most of the catalytic active site (Ni) remains present during the DRM reaction over all catalyst systems. Upon Y addition, the tetragonal zirconia-yttrium oxide phase stabilizes the support. Gadolinium promotional addition up to 4 wt % modifies the surface by formation of the cubic zirconium gadolinium oxide phase, limits the size of NiO, and makes reducible NiO moderately interacted species available over the catalyst surface and resists coke deposition. The 5Ni4Gd/Y + Zr catalyst shows about ∼80% yield of hydrogen constantly up to 24 h at 800 °C.

Overexpression, purification, crystallization and preliminary X-ray analysis of putative molybdenum cofactor biosynthesis protein C (MoaC2) from Mycobacterium tuberculosis H37Rv.

Rv0864 (MoaC2) from Mycobacterium tuberculosis is one of the enzymes in the molybdenum cofactor (Moco) biosynthesis pathway. Together with MoaA, MoaC is involved in the conversion of guanosine triphosphate (GTP) to precursor Z, the first step in Moco synthesis. Full-length MoaC2 (17.5 kDa, 167 residues) was cloned in Escherichia coli and purified to homogeneity. Crystals of recombinant M. tuberculosis MoaC2 were grown by vapour diffusion using a hanging-drop setup. Diffracting crystals grew in a condition in which 3 µl protein solution at 10.5 mg ml(-1) was mixed with 1.5 µl reservoir solution (0.025 M potassium sodium tartrate tetrahydrate pH 8.0) and equilibrated against 1000 µl reservoir solution. Diffraction data extending to 2.5 Å resolution were collected at 100 K. The crystal belonged to the cubic space group P2(1)3, with unit-cell parameter 94.5 Å. Matthews coefficient (V(M)) calculations suggested the presence of two molecules in the asymmetric unit, corresponding to a solvent content of about 39%. Molecular-replacement calculations using the E. coli homologue as the search model gave an unambiguous solution.

Endogenous cysteine protease inhibitors in upmost pathogenic parasitic protozoa.

The regulation of the activity of proteases by endogenous inhibitors is a common trend in almost all forms of life. Here, we review the endogenous inhibitors of cysteine proteases of three major pathogenic parasitic protozoa. The review focuses on members of the genus Plasmodium, Entamoeba, and Leishmania. Research in this domain has revealed the presence of only chagasin-like inhibitors of cysteine proteases that house a ß-barrel immunoglobulin-fold and inhibit the target proteases using a 3-loop inhibitory mechanism in these pathogens. Inhibitors of cysteine proteases are highly evolvable enzymes that target a broad spectrum of pathogenic cysteine proteases with a proclivity for those involved in host-parasite interactions. A common trend reflects a limited sequence homology between cysteine proteases and their inhibitors. The inhibitors are also known to participate in other housekeeping functions of the parasites. Generalizations about their roles are thus best avoided. In this review, the reader will find comprehensive information on the cellular localization of inhibitors of cysteine proteases, their structure, function, and the associated mechanisms of action. The reader will also find a thorough analysis of the role of these inhibitors in parasite pathology and the common trends interlinking them with parasite biology and evolution.

Identification of Protein Drug Targets of Biofilm Formation and Quorum Sensing in Multidrug Resistant Enterococcus faecalis.

Enterococcus faecalis (E. faecalis) is an opportunistic multidrug-resistant (MDR) pathogen found in the guts of humans and farmed animals. Due to the occurrence of (MDR) strain there is an urgent need to look for an alternative treatment approach. E. faecalis is a Gram-positive bacterium, which is among the most prevalent multidrug resistant hospital pathogens. Its ability to develop quorum sensing (QS) mediated biofilm formation further exacerbates the pathogenicity and triggers lifethreatening infections. Therefore, developing a suitable remedy for curing E. faecalis mediated enterococcal infections is an arduous task. Several putative virulence factors and proteins are involved in the development of biofilms in E. faecalis. Such proteins often play important roles in virulence, disease, and colonization by pathogens. The elucidation of the structure-function relationship of such protein drug targets and the interacting compounds could provide an attractive paradigm towards developing structure-based drugs against E. faecalis. This review provides a comprehensive overview of the current status, enigmas that warrant further studies, and the prospects toward alleviating the antibiotic resistance in E. faecalis. Specifically, the role of biofilm and quorum sensing (QS) in the emergence of MDR strains had been elaborated along with the importance of the protein drug targets involved in both the processes.

Deciphering the Role of S-adenosyl Homocysteine Nucleosidase in Quorum Sensing Mediated Biofilm Formation.

S-adenosylhomocysteine nucleosidase (MTAN) is a protein that plays a crucial role in several pathways of bacteria that are essential for its survival and pathogenesis. In addition to the role of MTAN in methyl-transfer reactions, methionine biosynthesis, and polyamine synthesis, MTAN is also involved in bacterial quorum sensing (QS). In QS, chemical signaling autoinducer (AI) secreted by bacteria assists cell to cell communication and is regulated in a cell density-dependent manner. They play a significant role in the formation of bacterial biofilm. MTAN plays a major role in the synthesis of these autoinducers. Signaling molecules secreted by bacteria, i.e., AI-1 are recognized as acylated homoserine lactones (AHL) that function as signaling molecules within bacteria. QS enables bacteria to establish physical interactions leading to biofilm formation. The formation of biofilm is a primary reason for the development of multidrug-resistant properties in pathogenic bacteria like Enterococcus faecalis (E. faecalis). In this regard, inhibition of E. faecalis MTAN (EfMTAN) will block the QS and alter the bacterial biofilm formation. In addition to this, it will also block methionine biosynthesis and many other critical metabolic processes. It should also be noted that inhibition of EfMTAN will not have any effect on human beings as this enzyme is not present in humans. This review provides a comprehensive overview of the structural-functional relationship of MTAN. We have also highlighted the current status, enigmas that warrant further studies, and the prospects for identifying potential inhibitors of EfMTAN for the treatment of E. faecalis infections. In addition to this, we have also reported structural studies of EfMTAN using homology modeling and highlighted the putative binding sites of the protein.

Targeting COPD with PLGA-Based Nanoparticles: Current Status and Prospects.

Chronic obstructive pulmonary disease (COPD) is pulmonary emphysema characterized by blockage in the airflow resulting in the long-term breathing problem, hence a major cause of mortality worldwide. Excessive generation of free radicals and the development of chronic inflammation are the major two episodes underlying the pathogenesis of COPD. Currently used drugs targeting these episodes including anti-inflammatory, antioxidants, and corticosteroids are unsafe, require high doses, and pose serious side effects. Nanomaterial-conjugated drugs have shown promising therapeutic potential against different respiratory diseases as they are required in small quantities which lower overall treatment costs and can be effectively targeted to diseased tissue microenvironment hence having minimal side effects. Poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) are safe as their breakdown products are easily metabolized in the body. Drugs loaded on the PLGA NPs have been shown to be promising agents as anticancer, antimicrobial, antioxidants, and anti-inflammatory. Surface modification of PLGA NPs can further improve their mechanical properties, drug loading potential, and pharmacological activities. In the present review, we have presented a brief insight into the pathophysiological mechanism underlying COPD and highlighted the role, potential, and current status of PLGA NPs loaded with drugs in the therapy of COPD.