Identification of coastal pesticide pollutants as potent inhibitors of Bacillus pasteurii urease mediated calcium carbonate precipitation: a computational approach.

Microbially induced calcite precipitation (MICP) through urease enzyme has attained a lot of recognition in various fields of civil engineering and geotechnology for stabilizing the strength of soil and various concrete materials. The activity of urease has been found to be affected by various factors like temperature, substrate concentrations, pH of the medium, presence of inhibitors, etc. Through this study, the outcome of the interaction of pesticides (commonly found in Indian coastal regions) on Bacillus pasteurii urease, a major organism reported for MICP studies has been investigated in silico. The results from the study revealed that the enzyme has higher interactions of -4.1, -3.2, and -3.4 kJ/mol with common pesticides like dichloro diphenyl dichloro ethane(DDD), dichloro diphenyl trichloroe thane (DDT), and methyl parathion of organochlorides and organophosphates class. From the molecular dynamics simulation analysis, complex 1 (DDD -receptor) has been found to have the highest and more compact structure followed by methyl parathion -receptor. Prime MM-GBSA analysis also revealed the highest binding energy of -27.8 kcal/mol with the protein and DDD. Thus, it can be inferred from the current study that pesticides, particularly, DDD, DDT, and methyl parathion present in the coastal areas may have an impact on urease. This interaction can result in the inhibition of the urease activity of B. pasteurii, thus preventing the biomineralization process. This study would be the first report on the computational approach to understanding the interaction of prominent pesticides on the coastal region and B. pasteurii urease.Communicated by Ramaswamy H. Sarma.

Targeting BRF2: insights from in silico screening and molecular dynamic simulations.

The Transcription factor II B (TFIIB)­related factor 2 (BRF2) containing TFIIIB complex recruits RNA polymerase III multi-subunit complex to selective gene promoters that altogether are responsible for synthesizing a variety of small non-coding RNAs, including a special type of selenocysteine tRNA (tRNASec), micro-RNA (miRNA), and other regulatory RNAs. BRF2 has been identified as a potential oncogene that promotes cancer cell survival under oxidative stress through its genetic activation. The structure of the BRF2 protein was modeled using the Robetta server, refined, and validated using the Ramachandran plot. A virtual approach utilizing molecular docking was used to screen a natural compound library to determine potential compounds that can interact with the molecular pin motif of the BRF2 protein using Maestro (Schrodinger). Subsequent molecular dynamics simulation studies of the top four ligands that exhibited low glide scores were performed using GROMACS. The findings derived from the simulations, in conjunction with the exploration of hydrogen bonding patterns, evaluation of the free energy landscape, and thorough analysis of residue decomposition, collectively converged to emphasize the robust interaction characteristics exhibited by Ligand 366 (Deacetyl lanatoside C) and ligand 336 (Neogitogenin)-with the BRF2 protein. These natural compounds may be potential inhibitors of BRF2, which could modulate the regulation of selenoprotein synthesis in cancer cells. Targeting BRF2 using these promising compounds may offer a new therapeutic approach to sensitize cancer cells to ferroptosis and apoptosis.Communicated by Ramaswamy H. Sarma.

Total Synthesis of Pyrrolidine and Piperidine Natural Products via TMSOTf-Mediated "5/6-endo-dig" Reductive Hydroamination of Enynyl Amines.

Stereoselective syntheses of pyrrolidines and piperidines bearing hydrophobic chains have been achieved through a metal free, Lewis acid-mediated 5/6-endo-dig reductive hydroamination cascade of enynyl amines. The brevity of the developed strategy allowed for the collective stereoselective total synthesis of various alkaloids, including (±)-pyrrolidine cis-225H, (±)-epi-197B, (±)-epi-225C, the family of (+)-solenopsins and (+)-isosolenopsins, and the formal synthesis of (±)-bgugaine and (+)-azimic acid.

Dynamic matrices with DNA-encoded viscoelasticity for cell and organoid culture.

Three-dimensional cell and organoid cultures rely on the mechanical support of viscoelastic matrices. However, commonly used matrix materials lack control over key cell-instructive properties. Here we report on fully synthetic hydrogels based on DNA libraries that self-assemble with ultrahigh-molecular-weight polymers, forming a dynamic DNA-crosslinked matrix (DyNAtrix). DyNAtrix enables computationally predictable and systematic control over its viscoelasticity, thermodynamic and kinetic parameters by changing DNA sequence information. Adjustable heat activation allows homogeneous embedding of mammalian cells. Intriguingly, stress-relaxation times can be tuned over four orders of magnitude, recapitulating mechanical characteristics of living tissues. DyNAtrix is self-healing, printable, exhibits high stability, cyto- and haemocompatibility, and controllable degradation. DyNAtrix-based cultures of human mesenchymal stromal cells, pluripotent stem cells, canine kidney cysts and human trophoblast organoids show high viability, proliferation and morphogenesis. DyNAtrix thus represents a programmable and versatile precision matrix for advanced approaches to biomechanics, biophysics and tissue engineering.

Identification of CXCR4 inhibitors as a key therapeutic small molecule in renal fibrosis.

The final stage of almost all chronic kidney diseases is renal fibrosis. Simple wounds or persistent inflammation can cause tissue inflammation, which, in the case of the kidney, results in scarring. Vascular sclerosis, tubulointerstitial fibrosis and glomerular fibrosis are all types of kidney fibrosis. Renal damage and fibrosis are caused by elevated expression of CXCR4. This study aimed to identify possible pharmacological agents which could bind to and inhibit isoform I of CXCR4 and determine their strength of interactions. The I-TASSER, Galaxyweb and Robetta were used to predict and refine the structure of the CXCR4 protein. ModBase was used to improve the loops, and then the quality was evaluated by using the ERRAT value (92.15) and Ramachandran plot. The improved 3D structure was subjected to small molecule database docking using Maestro (from Schrodinger) and the glide module. GROMACS was used to simulate molecules with the three top low glide scores and the best ADME properties. The best glide score was achieved by ligand ID 4990 (-11.5). Simulations, free energy landscape and residue decomposition analysis revealed that 4990 interacted more consistently with CXCR4 than the other two small molecules.Communicated by Ramaswamy H. Sarma.

Cu(II)/PTABS-Promoted, Regioselective SNAr Amination of Polychlorinated Pyrimidines with Mechanistic Understanding.

Regioselective amination of polyhalogenated heteroarenes (especially pyrimidines) has extensive synthetic and commercial relevance for drug synthesis applications but is plagued by the lack of effective synthetic strategies. Herein, we report the Cu(II)/PTABS-promoted highly regioselective nucleophilic aromatic substitution (SNAr) of polychlorinated pyrimidines assisted by DFT predictions of the bond dissociation energies of different C-Cl bonds. The unique reactivity of Cu(II)-PTABS has been attributed to the coordination/activation mechanism that has been known to operate in these reactions, but further insights into the catalytic species have also been provided.

Heavy and less common metals in rainwater and the kinetics of the oxidation of hydrogen sulfide by oxygen in rainwater medium.

As a sequel to our recent study on the oxidation by O2, i. e., autoxidation of dissolved hydrogen sulfide, H2S, in aqueous medium, we present here the results of a similar study in rain water medium. The rainwater sampling was done sequentially for four years (2016-2019). In all 67 samples of rainwater were collected on event basis during monsoon period (June-October) in and around the Campus of University of Rajasthan, Jaipur (26°50̛ N-75°52̛ E), which is situated in a semi-arid region adjacent to the Thar Desert in the North-Western part of the India having an annual average rainfall of 54 cm. ICP-MS technique was used in the analysis of rainwater and more than 30 metals were detected, which included transition metals, rare earths, less common metals. Beryllium, vanadium, silver, selenium, manganese, cerium, gallium, yttrium, barium, cesium, copper, rubidium, arsenic, lanthanum, cadmium, lead, uranium and bismuth were common to all rain water samples.H2S oxidation by dissolved oxygen was studied in rainwater as well as in laboratory water media for comparison. The kinetics rate law was: -d[O2]/dt = k1K1[H+][S][O2]t/( [H+]2 + K1[H+] + K1K2), where K1 is first dissociation constant of H2S and k1 is the rate constant for the dominant reaction step:HS- + O2 → products.

Molecular Interactions between APIs and Enteric Polymeric Excipients in Solid Dispersion: Insights from Molecular Simulations and Experiments.

Solid dispersion of poorly soluble APIs is known to be a promising strategy to improve dissolution and oral bioavailability. To facilitate the development and commercialization of a successful solid dispersion formulation, understanding of intermolecular interactions between APIs and polymeric carriers is essential. In this work, first, we assessed the molecular interactions between various delayed-release APIs and polymeric excipients using molecular dynamics (MD) simulations, and then we formulated API solid dispersions using a hot melt extrusion (HME) technique. To assess the potential API-polymer pairs, three quantities were evaluated: (a) interaction energy between API and polymer [electrostatic (Ecoul), Lenard-Jones (ELJ), and total (Etotal)], (b) energy ratio (API-polymer/API-API), and (c) hydrogen bonding between API and polymer. The Etotal quantities corresponding to the best pairs: NPX-Eudragit L100, NaDLO-HPMC(P), DMF-HPMC(AS) and OPZ-HPMC(AS) were -143.38, -348.04, -110.42, and -269.43 kJ/mol, respectively. Using a HME experimental technique, few API-polymer pairs were successfully extruded. These extruded solid forms did not release APIs in a simulated gastric fluid (SGF) pH 1.2 environment but released them in a simulated intestinal fluid (SIF) pH 6.8 environment. The study demonstrates the compatibility between APIs and excipients, and finally suggests a potential polymeric excipient for each delayed-release API, which could facilitate the development of the solid dispersion of poorly soluble APIs for dissolution and bioavailability enhancement.

In silico identification of a promising inhibitor of Fusarium oxysporum f. sp. Lycopersici, Secreted in Xylem 1 protein.

Fusarium oxysporum f. sp. Lycopersici (FOL) is a soilborne pathogen that infects tomato plants and inflicts severe damage, resulting in heavy yield losses worldwide, causing Fusarium wilt disease. FOL encodes several pathogenicity factors necessary for colonizing and invading the host plants. Secreted in Xylem (SIX), a pathogenicity factor, is a small cysteine-rich fungal protein found in the xylem sap of FOL-infected tomato plants, which plays a major role in determining host specificity and in contributing to pathogenicity/virulence. However, the structure of SIX1 has not been modeled yet. Therefore, this study aimed to elucidate the structure of SIX1 by comparative modeling using Robetta server. The best possible structures obtained were then refined, validated, and utilized for subsequent analysis. An antifungal library comprising 16,824 compounds was screened to determine small molecules that can interact with SIX1. Five antifungal compounds were identified from the library. Further analyses revealed that, of the five ligands, 4-[(2-(3-methoxyphenoxy)acetyl)amino] benzamide exhibited the capacity to stably interact with SIX1. This shows that 4-[[2-(3-methoxyphenoxy)acetyl]amino] benzamide can be used as a potential candidate in the prevention of FOL infection. In summary, small-molecule inhibitors such as 4-[[2-(3-methoxyphenoxy)acetyl]amino] benzamide could be highly effective in combating FOL infection, along with biocontrol methods and strategies that use transgenic plants overexpressing resistance genes.

Development of a smart pH-responsive nano-polymer drug, 2-methoxy-4-vinylphenol conjugate against the intestinal pathogen, Vibrio cholerae.

Vibrio cholerae causes cholera, an acute diarrhoeal disease. The virulence in V. cholerae is regulated by the quorum-sensing mechanism and response regulator LuxO positively regulates the expression of virulence determinants adhesion, biofilm formation, and cholera toxin production. Previous in-silico studies revealed that 2-methoxy-4-vinylphenol could bind to the ATP binding site of LuxO and the complex was compact and stable in pHs like intestinal pHs. Here, we have explored the polymeric nano-formulation of 2-methoxy-4-vinylphenol using cellulose acetate phthalate for controlled drug release and their effectiveness in attenuating the expression of V. cholerae virulence. Physico-chemical characterization of the formulation showed particles with a mean size of 91.8 ± 14 nm diameter and surface charge of - 14.7 ± 0.07 mV. The uniform round polymeric nanoparticles formed displayed about 51% burst release of the drug at pH 7 by 3rd h, followed by a controlled linear release in alkaline pH. The polymeric nanoparticles demonstrated a tenfold increase in intestinal membrane permeability ex-vivo. At lower concentrations, the 2-methoxy-4-vinylphenol polymeric nanoparticles were non-cytotoxic to Int 407 cells. In-vitro analysis at pH 6, pH 7, pH 8, and pH 9 revealed that cellulose acetate phthalate-2-methoxy-4-vinylphenol nanoparticles were non-bactericidal at concentrations up to 500 µg/mL. At 31.25 µg/mL, the nanoparticles inhibited about 50% of the biofilm formation of V. cholerae MTCC 3905 and HYR14 strains. At this concentration, the adherence of V. cholerae MTCC 3905 and HYR14 to Int 407 cell lines were also significantly affected. Gene expression analysis revealed that the expression of tcp, qrr, and ct at pH 6, 7, 8, and 9 has reduced. The CAP-2M4VP nanoparticles have demonstrated the potential to effectively reduce the virulence of V. cholerae in-vitro.

Formulation and Skin Permeation of Active-Loaded Lipid Nanoparticles: Evaluation and Screening by Synergizing Molecular Dynamics Simulations and Experiments.

Encapsulation into nanoparticles (NPs) is a potential method to deliver pharmaceutical/cosmetic actives deep into the skin. However, understanding the NP formulations and underlying mechanism of active delivery to skin has scarcely been studied. We report a simulation platform that screens, evaluates, formulates, and provides atomic-resolution interpretation of NP-based formulations, and reveals the active permeation mechanism from NPs to skin. First, three actives, namely, ferulic acid (FA), clotrimazole (CZE), and tretinoin (TTN), and five lipid excipients' (Compritol, Precirol, Geleol, Gelot, Gelucire) combinations were screened by MD simulations for the best pairs. For each suggested pair, the actual active and lipid compositions for the synthesis of stable NP formulations were then obtained by experiments. MD simulations demonstrate that in NP formulations, FA and CZE actives are present at the surface of the NPs, whereas TTN actives are present at both the surface and interior of the NP core. The NP shapes obtained by simulation perfectly match with experiments. For each NP, separate MD simulations illustrate that active-loaded NPs approach the skin surface quickly, and then actives translocate from NP surface to skin surface followed by penetration of NPs through skin. The driving force for the translocation which initiates during the penetration process, is the stronger active-skin interaction compared to active-NP interaction. Permeation free energy indicates spontaneous transfer of actives from solution phase to the surface of the skin bilayer. The free energy barriers are increased in the order of FA < TTN < CZE. Significantly lower diffusions of actives are obtained in the main barrier region compared to bulk, and the average diffusion coefficients of actives are in the same order of magnitude (∼10-6 cm2/s). The estimated permeability coefficients (log P) of actives are mainly governed by free energy barriers. The study would facilitate the development of novel lipid-based NP formulations for personal-care/pharmaceutical applications.

Refractive Error among Children Visiting the Department of Paediatric Opthalmology of a Tertiary Eye Care Center.

Introduction: Refractive error is the inability of eyes to focus clearly on images. Visual impairment due to refractive error has a major impact on children's education and daily activities. The hospital has no documentation of the ocular morbidity related to refractive errors in children. The aim of this study was to find out the prevalence of refractive error in children visiting the Department of Paediatric Ophthalmology of a tertiary care centre. Methods: A descriptive cross-sectional study was done in the Outpatient Department of Paediatric Ophthalmology in a tertiary care centre from 8 September 2022 to 7 March 2023 after obtaining ethical approval from the Institutional Review Committee. A convenience sampling method was used. The point estimate was calculated at 95% Confidence Interval. Results: Among 3600 children, the prevalence of refractive error was seen in 668 children (18.56%) (15.61-21.51, 95% Confidence Interval). Refractive error was seen in 363 (54.34%) boys and 305 (45.66%) girls. Myopia was found in 340 (50.90%), astigmatism in 207 (30.99%), and hyperopia in 121 (18.11%). Conclusions: The prevalence of refractive error among children attending a tertiary care centre was found to be higher than studies done in similar settings. Regular screening of refractive error for visual impairment is recommended among school going children. Keywords: astigmatism; hyperopia; myopia; refractive error; visual impairment.

Transposition of an acrylate moiety in TMSOTf-mediated reaction of alkynyl vinylogous carbonates gives heterocyclic dienes.

TMSOTf-mediated reaction of alkynyl vinylogous carbonates serendipitously gave 1,4-oxazepine and dihydropyran dienes via transposition of an ethyl acrylate moiety involving intramolecular cascade Prins-type cyclization/retro-oxa-Michael reaction/cycloisomerisation. The developed atom-economical protocol selectively provides an E double bond geometry. Dihydropyran dienes could be reduced diastereoselectively using Et3SiH/TMSOTf or could be transformed into polycyclic heterocycles by Heck reaction.

Prevalence of Retinitis Pigmentosa in a Tertiary Eye Hospital of Nepal.

INTRODUCTION: Retinitis Pigmentosa (RP) is a group of diffuse retinal degenerative diseases predominantly affecting the rod and cone photoreceptors. The prevalence of retinitis pigmentosa seen in literature is approximately 1:4000. Retinitis Pigmentosa is one of the the most common causes of blindness in the age group of 20 to 40 years. The objective of this study was to determine the profile of retinitis pigmentosa in Terai and Nepal-India border region considering patients seeking care at a Tertiary level Eye Hospital in the terai region (southern part) of Nepal. MATERIALS AND METHODS: A hospital-based, retrospective study was carried out at R. M. Kedia Eye Hospital. A total of 385 (83 males and 107 females from Nepal and 109 males and 86 females from India) diagnosed patients of Retinitis Pigmentosa were included in the study. Data was collected over a period of eleven years from 2008-2018. RESULTS: Out of 385 diagnosed Retinitis Pigmentosa patients, 192 (49.87%) were male and 193 (50.13%) were female with slightly female predominance. The prevalence of RP seen in our study was 0.03%. About 51% of the patients visited here were from India and nearby border areas/ villages which cover most of the rural areas of India. In this study it was found that 49.34% of the RP cases were from Nepal, of which 43.63% of cases were from Hindu community and 5.71% from Muslim community and about 50.66% cases of RP were from India, of which 37.67% from Hindu and 12.98% from Muslim community. The peak age of presentation of RP was at 30-39 years (29.09%), followed by 20-29 years (26.75%). The common marriage pattern of consanguinity was found in Muslim community in between the first cousins. In this study the hospital record did not show any evaluation for the syndromic disease in the hospital record, though RP is usually non syndromic and there are literatures where many syndromic forms have been identified. CONCLUSION: The prevalence of RP seen in the study was 0.03% (A total of 1101299 sample population of which 385 patients had RP). Since RP is an inherited disease and is one of the non-treatable causes of blindness which runs in the families, a role of counseling to reduce consanguineous marriages should be brought forward to reduce the disease process.

Optimizing Friction Stir Welding of Dissimilar Grades of Aluminum Alloy Using WASPAS.

Aluminum is a widely popular material due to its low cost, low weight, good formability and capability to be machined easily. When a non-metal such as ceramic is added to aluminum alloy, it forms a composite. Metal Matrix Composites (MMCs) are emerging as alternatives to conventional metals due to their ability to withstand heavy load, excellent resistance to corrosion and wear, and comparatively high hardness and toughness. Aluminum Matrix Composites (AMCs), the most popular category in MMCs, have innumerable applications in various fields such as scientific research, structural, automobile, marine, aerospace, domestic and construction. Their attractive properties such as high strength-to-weight ratio, high hardness, high impact strength and superior tribological behavior enable them to be used in automobile components, aviation structures and parts of ships. Thus, in this research work an attempt has been made to fabricate Aluminum Alloys and Aluminum Matrix Composites (AMCs) using the popular synthesis technique called stir casting and join them by friction stir welding (FSW). Dissimilar grades of aluminum alloy, i.e., Al 6061 and Al 1100, are used for the experimental work. Alumina and Silicon Carbide are used as reinforcement with the aluminum matrix. Mechanical and corrosion properties are experimentally evaluated. The FSW process is analyzed by experimentally comparing the welded alloys and welded composites. Finally, the best suitable FSW combination is selected with the help of a Multi-Attribute Decision Making (MADM)-based numerical optimization technique called Weighted Aggregated Sum Product Assessment (WASPAS).

Perception towards Online Teaching-learning in Medical Education among Medical Students during COVID-19 Outbreak in Nepal: A Descriptive Cross-sectional Study.

INTRODUCTION: The outbreak of coronavirus disease in Nepal led medical colleges to suspend in person teaching-learning activities and ultimately online platform was introduced to deliver the contents of medical education. The objective of this study was to describe the perception of medical students towards online teaching-learning introduced during the COVID-19 outbreak in Nepal. METHODS: An online survey using a descriptive cross-sectional study design was carried out among 515 undergraduate medical students currently enrolled in medical colleges in Nepal. Ethical approval was sought from Nepal Health Research Council to conduct this study, and digital informed consent was taken from study respondents. A semi-structured questionnaire in Google form was utilized to collect data. The link of the Google form was sent to the potential respondents through email and social media. Descriptive statistics, including frequency, percentage, mean, and standard deviation were used to analyze data in Stastical Package for the Social Sciences version 20. Ethical approval was sought from Nepal Health Research Council to conduct this study, and digital informed consent was taken from study respondants. RESULTS: The overall score of perception of online teaching-learning was 17.61±7.19, which indicated many problems in this method of teaching-learning. The mean score of perception of online teaching-learning was found to be different across sex, location of enrolled medical colleges, having a personal electronic device, having an internet connection at residence, having separate room/space for attending online classes, and self-rated computer skills. Moreover, only 28 (5.4%) of respondents had perceived online teaching-learning as a better method of delivering content of medical curricula. CONCLUSIONS: Surveyed medical students in Nepal were found to perceive many problems in online teaching-learning. Moreover, management and faculty members need to take the necessary measures for enhancing the online teaching-learning quality.

Molecular dynamics simulations to elucidate translocation and permeation of active from lipid nanoparticle to skin: complemented by experiments.

One of the most realistic approaches for delivering actives (pharmaceuticals/cosmetics) deep into skin layers is encapsulation into nanoparticles (NPs). Nonetheless, molecular-level mechanisms related to active delivery from NPs to the skin have scarcely been studied despite the large number of synthesis and characterization studies. We herein report the underlying mechanism of active translocation and permeation through the outermost layer of skin, the stratum corneum (SC), via molecular dynamics (MD) simulations complemented by experimental studies. A SC molecular model is constructed using current state-of-the-art methodology via incorporating the three most abundant skin lipids: ceramides, free fatty acids, and cholesterol. As a potent antioxidant, ferulic acid (FA) is used as the model active, and it is loaded into Gelucire 50/13 NP. MD simulations elucidate that, first, FA-loaded NP approaches the skin surface quickly, followed by slight penetration and adsorption onto the upper skin surface; FA then translocates from the NP surface to the skin surface due to stronger NP-skin interactions compared to the FA-NP interactions; then, once FA is released onto the skin surface, it slowly permeates deep into the skin bilayer. Both the free energy and resistance to permeation not only indicate the spontaneous transfer of FA from the bulk to the skin surface, but they also reveal that the main barrier against permeation exists in the middle of the lipid hydrophobic tails. Significantly lower diffusion of FA is obtained in the main barrier region compared to the bulk. The estimated permeability coefficient (log P) values are found to be higher than the experimental values. Importantly, the permeation process evaluated via MD simulations perfectly matches with experiments. The study suggests a molecular simulation platform that provides various crucial insights relating to active delivery from loaded NP to skin, and it could facilitate the design and development of novel NP-based formulations for transdermal delivery and the topical application of drugs/cosmetics.

A Review on Pharmacokinetics Properties of Antiretroviral Drugs to Treat HIV-1 Infections.

BACKGROUND: The HIV-1 pandemic is undoubtedly the major public-health crisis of our time. The extensive research on HIV has deepened our understanding of its pathogenesis and transmission dynamics. Some new entity molecules have been approved by the FDA for HIV treatment, but till now, the protective vaccine remains elusive. Scientists are targeting many important proteins of HIV-1; gp41, gp120, CCR5 coreceptor, integrase, reverse transcriptase and protease. Few compounds are used as nucleotide analogues to stop HIV replication. Altogether, these compounds and their derivatives specifically block HIV entry and DNA replication. Using ADMET studies, people are working on these compounds to reduce toxicity and increase potency. OBJECTIVES: Our main aim is to discuss the Pharmacokinetics properties of 23 important FDA antiretroviral drugs used for the treatment of HIV-1 infections. METHODS: We have searched literature related to pharmacokinetics properties in PubMed, Google Scholar search engine. CONCLUSION: Here, we have reviewed the pharmacokinetic properties such as absorption, bioavailability, distribution, metabolism, and excretion of 23 important FDA-approved drugs. These drugs are Fuzeon, Selzentry, Complera, Epivir, Retrovir, Emtriva, Ziagen, Edurant, Intelence, Pifeltro, Sustiva, Viramune, Isentress, Genvoya, Tivicay, Reyataz, Prezista, Lexiva, Invirase, Aptivus etc. classified into five major classes: fusion inhibitors, Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs), Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs), Integrase Strand transfer inhibitors (INSTIs) and Protease inhibitors (PIs). This review may be helpful for the future development of potent antiretroviral drugs with improved pharmacokinetic properties.