Current progress in CRISPR-Cas systems for cancer.

Cancer has been a primary contributor to morbidity and mortality worldwide. With an increasing trend of incidence and prevalence of cancer, progress has also been made in its treatment, starting from radiation and chemotherapy to immunotherapy and gene therapy. CRISPR-Cas technique, a promising gene editing tool, has been employed in cancer research for novel treatment regimens, identification of therapeutic targets, and unraveling the genetic mechanisms behind oncogenesis. CRISPR-based genome editing helped in identifying the roles of specific genetic factors linked to treatment resistance, metastasis, and cancer development. CRISPR allows the discovery of genes and treatment options through specifically interrupting tumor activators or activating tumor suppressor genes in cancer cells. Advancements in CRISPR technology, especially the use of immune cells like chimeric antigen receptor (CAR) T cells, has the potential to revolutionize personalized cancer treatment by precisely targeting and killing cancer cells. Furthermore, reactivating tumor suppressor genes makes cancer cells more susceptible to chemotherapy or immunotherapy. CRISPR-mediated genome editing can, hence, help to overcome resistance to traditional cancer treatments. The current manuscript covers that how is the CRISPR technology propelling revolutionary development in the field of cancer research, providing advance perspectives on the molecular causes of the disease and creating new lines for the development of more precise and potent cancer therapies.

Advances in CRISPR-Cas systems for epigenetics.

The CRISPR-Cas9 method has revolutionized the gene editing. Epigenetic changes, including DNA methylation, RNA modification, and changes in histone proteins, have been intensively studied and found to play a key role in the pathogenesis of human diseases. CRISPR-While the utility of DNA and chromatin modifications, known as epigenetics, is well understood, the functional significance of various alterations of RNA nucleotides has recently gained attention. Recent advancements in improving CRISPR-based epigenetic modifications has resulted in the availability of a powerful source that can selectively modify DNA, allowing for the maintenance of epigenetic memory over several cell divisions. Accurate identification of DNA methylation at specific locations is crucial for the prompt detection of cancer and other diseases, as DNA methylation is strongly correlated to the onset as well as the advancement of such conditions. Genetic or epigenetic perturbations can disrupt the regulation of imprinted genes, resulting in the development of diseases. When histone code editors and DNA de-/ methyltransferases are coupled with catalytically inactive Cas9 (dCas9), and CRISPRa and CRISPRi, they demonstrate excellent efficacy in editing the epigenome of eukaryotic cells. Advancing and optimizing the extracellular delivery platform can, hence, further facilitate the manipulation of CRISPR-Cas9 gene editing technique in upcoming clinical studies. The current chapter focuses on how the CRISP/ Cas9 system provides an avenue for the epigenetic modifications and its employability for human benefit.

Intranasal delivery of liposome encapsulated flavonoids ameliorates l-DOPA induced dyskinesia in hemiparkinsonian mice.

In the present study, we explored the development of a novel noninvasive liposomal drug delivery material for use in intranasal drug delivery applications in human diseases. We used drug entrapment into liposomal nanoparticle assembly to efficiently deliver the drugs to the nasal mucosa to be delivered to the brain. The naturally occurring flavonoid 7,8-dihydroxyflavone (7,8-DHF) has previously been shown to have beneficial effects in ameliorating Parkinson's disease (PD). We used both naturally occurring 7,8-DHF and the chemically modified form of DHF, the DHF-ME, to be used as a drug candidate for the treatment of PD and l-DOPA induced dyskinesia (LID), which is the debilitating side effect of l-DOPA therapy in PD. The ligand-protein interaction behavior for 7,8-DHF and 6,7-DHF-ME was found to be more effective with molecular docking and molecular stimulation studies of flavonoid compounds with TrkB receptor. Our study showed that 7,8-DHF delivered via intranasal route using a liposomal formulation ameliorated LID in hemiparkinsonian mice model when these mice were chronically administered with l-DOPA, which is the only current medication for relieving the clinical symptoms of PD. The present study also demonstrated that apart from reducing the LID, 7,8-DHF delivery directly to the brain via the intranasal route also corrected some long-term signaling adaptations involving ΔFosB and α Synuclein in the brain of dopamine (DA) depleted animals.

Drug repurposing for bacterial infections.

Repurposing pharmaceuticals is a technique used to find new, alternate clinical applications for approved drug molecules. It may include altering the drug formulation, route of administration, dose or the dosage regimen. The process of repurposing medicines starts with screening libraries of previously approved drugs for the targeted disease condition. If after an the initial in silico, in vitro or in vivo experimentation, the molecule has been found to be active against a particular target, the molecule is considered as a good candidate for clinical trials. As the safety profile of such molecules is available from the previous data, significant time and resources are saved. These advantages of drug repurposing approach make it especially helpful for finding treatments for rapidly evolving conditions including bacterial infections. An ever-increasing incidence of antimicrobial resistance, owing to the mutations in bacterial genome, leads to therapeutic failure of many approved antibiotics. Repurposing the approved drug molecules for use as antibiotics can provide an effective means for the combating life-threatening bacterial diseases. A number of drugs have been considered for drug repurposing against bacterial infections. These include, but are not limited to, Auranofin, Closantel, and Toremifene that have been repurposed for various infections. In addition, the reallocation of route of administration, redefining dosage regimen and reformulation of dosage forms have also been carried out for repurposing purpose. The current chapter addresses the drug discovery and development process with relevance to repurposing against bacterial infections.

Regulatory considerations and intellectual property rights of repurposed drugs.

Drug repurposing has emerged as a promising approach in the drug discovery and development process as it offers safe and effective therapeutic options in a time effective manner. Though the issues related to pre-clinical and clinical aspects of drug development process are greatly addressed during drug repurposing yet regulatory perspectives gain even more However, like traditional drug development the repurposed drugs face multiple challenges. Such challenges range from the patenting rights, novelty of repurposing, data and market exclusivity to affordability and equitable access to the patient population. In order to optimize the market access of repurposed drugs, regulatory organizations throughout the world have developed accelerated approval procedures. The regulatory bodies have recognized the importance of repurposing approaches and repurposed drugs. Regulatory bodies can encourage the development of repurposed drugs by providing incentives to pharmaceutical companies and more accessible and affordable repurposed agents for the general population. This chapter summarizes the regulatory and ethical considerations pertaining to the repurposed drugs and highlights a few cases of intellectual property rights for repurposed drugs that have helped improve patient's access to safe, efficacious and cost-effective therapeutic options.

Computational biology approaches for drug repurposing.

The drug discovery and development (DDD) process greatly relies on the data available in various forms to generate hypotheses for novel drug design. The complex and heterogeneous nature of biological data makes it difficult to utilize or gather meaningful information as such. Computational biology techniques have provided us with opportunities to better understand biological systems through refining and organizing large amounts of data into actionable and systematic purviews. The drug repurposing approach has been utilized to overcome the expansive time periods and costs associated with traditional drug development. It deals with discovering new uses of already approved drugs that have an established safety and efficacy profile, thereby, requiring them to go through fewer development phases. Thus, drug repurposing through computational biology provides a systematic approach to drug development and overcomes the constraints of traditional processes. The current chapter covers the basics, approaches and tools of computational biology that can be employed to effectively develop repurposing profile of already approved drug molecules.

Nano-elicitation and hydroponics: a synergism to enhance plant productivity and secondary metabolism.

MAIN CONCLUSION: This review has explored the importance of using a synergistic approach of nano-elicitation and hydroponics to improve plant growth and metabolite production. Furthermore, it emphasizes the significance of green nanotechnology and eco-friendly practices while utilizing this approach to promote the development of a sustainable agriculture system. Nano-elicitation stimulates metabolic processes in plants using nanoparticles (NPs) as elicitors. The stimulation of these biochemical processes can enhance plant yield and productivity, along with the production of secondary metabolites. Nanoparticles have garnered the attention of scientific community because of their unique characteristics, such as incredibly small size and large surface-to-volume ratio, which make them effective elicitors. Hydroponic systems, which optimize growing conditions to increase plant production, are typically used to study the effect of elicitors. By integrating these two approaches, the qualitative and quantitative output of plants can be increased while employing minimal resources. As the global demand for high-quality crops and bioactive compounds surges, embracing this synergistic approach alongside sustainable farming practices can pave the way for resilient agricultural systems, ensuring food security and fostering an eco-friendly environment.

Development of chitosan based ß-carotene mucoadhesive formulation for skin cancer treatment.

Mucopermeating nanoformulations can enhance mucosal penetration of poorly soluble drugs at their target site. In this work, thiolated chitosan (TCS)-lithocholic acid (LA) nanomicelles loaded with ß-carotene, a safe phytochemical with anticancer properties, were designed to improve the pharmaceutical and pharmacological drug profile. The TCS-LA nanomicelles were characterized by FTIR to confirm the presence of the thiol group that favors skin adhesion, and to corroborate the conjugation of hydrophobic LA with hydrophilic CS to form an amphiphilic polymer derivative. Their crystalline nature and thermal behavior were investigated by XRD and DSC analyses, respectively. According to DLS and TEM, their average size was <300 nm, and their surface charge was +27.0 mV. ß-carotene entrapment and loading efficiencies were 64 % and 58 %, respectively. In vitro mucoadhesion and ex vivo mucopenetration analyses further corroborated the potential of the nanoformulation to deliver the drug in a sustained manner under conditions mimicking cancer micro-environment. Anticancer studies in mice demonstrated that the loaded nanomicelles delayed skin cancer growth, as revealed by both morphological and biochemical parameters. Based on the results obtained herein, it can be concluded that drug-loaded TCS-LA is a novel, stable, effective and safe mucoadhesive formulation of ß-carotene for the potential treatment of skin cancer.

Molecular implications of glycosaminoglycans in diabetes pharmacotherapy.

Diabetes mellitus causes a wide range of metabolic derangements with multiple organ damage. The microvascular and macrovascular complications of diabetes result partly from the damage to the glycosaminoglycans (GAG) in the basement membrane. GAGs are negatively charged polysaccharides with repeating disaccharide units. They play a significant role in cellular proliferation and signal transduction. Destruction of extracellular matrix results in diseases in various organs including myocardial fibrosis, retinal damage and nephropathy. To substitute the natural GAGs pharmacotherapeutically, they have been synthesized by using basic disaccharide units. Among the four classes of GAGs, heparin is the most widely studied. Recent studies have revealed multiple significant GAG-protein interactions suggesting their use for the management of diabetic complications. Moreover, they can act as biomarkers for assessing the disease progression. A number of GAG-based therapeutic agents are being evaluated for managing diabetic complications. The current review provides an outline of the role of GAGs in diabetes while covering their interaction with different molecular players that can serve as targets for the diagnosis, management and prevention of diabetes and its complications. The medicinal chemistry and clinical pharmacotherapeutics aspects have are covered to aid in the establishment of GAG-based therapies as a possible avenue for diabetes.

Virtual screening and drug repositioning of FDA-approved drugs from the ZINC database to identify the potential hTERT inhibitors.

The length of the telomeres is maintained with the help of the enzyme telomerase constituting of two components, namely, a core reverse transcriptase protein (hTERT) and RNA (hTR). It serves as a significant and universal cancer target. In silico approaches play a crucial role in accelerating drug development processes, especially cancer drug repurposing is an attractive approach. The current study is aimed at the repurposing of FDA-approved drugs for their potential role as hTERT inhibitors. Accordingly, a library of 2,915 sets of FDA-approved drugs was generated from the ZINC database in order to screen for novel hTERT inhibitors; later on, these were subjected to molecular docking analysis. The top two hits, ZINC03784182 and ZINC01530694, were shortlisted for molecular dynamic simulation studies at 100 ns based on their binding scores. The RMSD, RMSF, Rg, SASA, and interaction energies were calculated for a 100-ns simulation period. The hit compounds were also analyzed for antitumor activity, and the results revealed promising cytotoxic activities of these compounds. The study has revealed the potential application of these drugs as antitumor agents that can be useful in treating cancer and can serve as lead compounds for further in vivo, in vitro, and clinical studies.

Development of mucoadhesive adapalene gel for biotherapeutic delivery to vaginal tissue.

Purpose: Alternate formulation strategies need to be devised for improving the absorption and bioavailability of drug molecules administered through the intravaginal route. Enhancing the coating of vaginal mucosa can aid the achievement of this goal. The aim of the current study is to develop a mucoadhesive formulation having adequate adhesiveness, spreading, and viscosity profiles that can ensure good tissue absorption of adapalene upon intravaginal application. Method: A combination of mucoadhesive agents has been employed, including Carbopol-934, HPMC K-15M, and xanthan gum, in varying ratios to formulate five different gels. Furthermore, a cost-effective UV-spectroscopic analytical method was developed to quantify the amount of adapalene in tested samples, both of in vitro and in vivo origin. The analytical method was validated for different parameters, including specificity, linearity, range, accuracy, precision, and ruggedness. The modified USP-II apparatus was used for dissolution studies, while in vivo pharmacokinetic validation was performed in a murine model. Result: Of all the tested formulations, on the basis of the rheo-mechanical attributes, ACX3 performed better than the rest, including the commercially available intravaginal reference product. ACX3 had an average adhesion time of 12 min and a spread diameter of 37 mm. It showed 35 mm as average distance travelled by the diluted sample for leakage assessment. The analytical method developed for the adapalene muco-adhesive gel was within the range for all the validation parameters. For further evaluating the performance of the formulation, dissolution studies were conducted in simulated vaginal conditions which showed 94.83% of drug release within 5 minutes, while on completion of 30 min, it was measured to be 92.90%. Moreover, approximately 67% of the administered drug was recovered after 5 min of administration as evaluated through tissue recovery procedures in mice. Conclusion: The study aided in development of a formulation which can enhance the muco-adhesion of the drug molecule, resulting in an improved pharmacokinetic profile. Moreover, it established an efficient assay method which can be employed for in vitro and in vivo quantification of adapalene in simulated and physiological fluids.

Pharmacoinformatics approaches in the discovery of drug-like antimicrobials of plant origin.

Medicinal plants have served as an important source for addressing the ailments of humans and animals alike. The emergence of advanced technologies in the field of drug discovery and development has helped in isolating various bioactive phytochemicals and developing them as drugs. Owing to their significant pharmacological benefits and minimum adverse effects, they not only serve as good candidates for therapeutics themselves but also help in the identification and development of related drug like molecules against various metabolic and infectious diseases. The ever-increasing diversity, severity and incidence of infectious diseases has resulted in an exaggerated mortality and morbidity levels. Geno-proteomic mutations in microbes, irrational prescribing of antibiotics, antimicrobial resistance and human population explosion, all call for continuous efforts to discover and develop alternated therapeutic options against the microbes. This review article describes the pharmacoinformatics tools and methods which are currently used in the discovery of bioactive phytochemicals, thus making the process more efficient and effective. The pharmacological aspects of the drug discovery and development process have also been reviewed with reference to the in silico activities. Communicated by Ramaswamy H. Sarma.

Vaccinomics-driven proteome-wide screening of Haemophilus influenzae for the prediction of common putative vaccine candidates.

Haemophilus influenzae colonizes the respiratory tract and is associated with life-threatening invasive infections. The recent rise in its global prevalence, even in the presence of multiple vaccines, indicates an urgent need to develop effective cross-strain vaccine strategies. Our work focused on identifying the universally conserved antigenic regions of H. influenzae that can be used to develop new vaccines. A variety of bioinformatics tools were applied for the comprehensive geno-proteomic analysis of H. influenzae type a strain, as reference serotype, through which subcellular localization, essentiality, virulence, and non-host homology were determined. B and T cell epitope mapping of the 3D protein structures were performed. Thereafter, molecular docking with HLA_DRB1*0101 and comparative genome analysis established the candidature of the identified regions. Based on the established vaccinomics criteria, five target proteins were predicted as novel vaccine candidates. Among these, nine epitopic regions that could regulate lymphocyte activity through strong protein-protein interactions were identified. Comparative genomic analysis revealed that the identified regions were highly conserved among the different strains of H. influenzae. Based on multiple immunogenic factors, five prioritized proteins and their predicted epitopes were identified as ideal common putative vaccine candidates against typeable strains.

Evaluating the cleavage efficacy of CRISPR-Cas9 sgRNAs targeting ineffective regions of Arabidopsis thaliana genome.

The CRISPR-Cas9 system has recently evolved as a powerful mutagenic tool for targeted genome editing. The impeccable functioning of the system depends on the optimal design of single guide RNAs (sgRNAs) that mainly involves sgRNA specificity and on-target cleavage efficacy. Several research groups have designed algorithms and models, trained on mammalian genomes, for predicting sgRNAs cleavage efficacy. These models are also implemented in most plant sgRNA design tools due to the lack of on-target cleavage efficacy studies in plants. However, one of the major drawbacks is that almost all of these models are biased for considering only coding regions of the DNA while excluding ineffective regions, which are of immense importance in functional genomics studies especially for plants, thus making prediction less reliable. In the present study, we evaluate the on-target cleavage efficacy of experimentally validated sgRNAs designed against diverse ineffective regions of Arabidopsis thaliana genome using various statistical tests. We show that nucleotide preference in protospacer adjacent motif (PAM) proximal region, GC content in the PAM proximal seed region, intact RAR and 3rd stem loop structures, and free accessibility of nucleotides in seed and tracrRNA regions of sgRNAs are important determinants associated with their high on-target cleavage efficacy. Thus, our study describes the features important for plant sgRNAs high on-target cleavage efficacy against ineffective genomic regions previously shown to give rise to ineffective sgRNAs. Moreover, it suggests the need of developing an elaborative plant-specific sgRNA design model considering the entire genomic landscape including ineffective regions for enabling highly efficient genome editing without wasting time and experimental resources.

Genome-scale meta-analysis of breast cancer datasets identifies promising targets for drug development.

BACKGROUND: Because of the highly heterogeneous nature of breast cancer, each subtype differs in response to several treatment regimens. This has limited the therapeutic options for metastatic breast cancer disease requiring exploration of diverse therapeutic models to target tumor specific biomarkers. METHODS: Differentially expressed breast cancer genes identified through extensive data mapping were studied for their interaction with other target proteins involved in breast cancer progression. The molecular mechanisms by which these signature genes are involved in breast cancer metastasis were also studied through pathway analysis. The potential drug targets for these genes were also identified. RESULTS: From 50 DEGs, 20 genes were identified based on fold change and p-value and the data curation of these genes helped in shortlisting 8 potential gene signatures that can be used as potential candidates for breast cancer. Their network and pathway analysis clarified the role of these genes in breast cancer and their interaction with other signaling pathways involved in the progression of disease metastasis. The miRNA targets identified through miRDB predictor provided potential miRNA targets for these genes that can be involved in breast cancer progression. Several FDA approved drug targets were identified for the signature genes easing the therapeutic options for breast cancer treatment. CONCLUSION: The study provides a more clarified role of signature genes, their interaction with other genes as well as signaling pathways. The miRNA prediction and the potential drugs identified will aid in assessing the role of these targets in breast cancer.

Classification and Computational Analysis of Arabidopsis thaliana Sperm Cell-Specific F-Box Protein Gene 3p.AtFBP113.

In plants, F-box proteins (FBPs) constitute one of the largest superfamilies of regulatory proteins. Most F-box proteins are shown to be an integral part of SCF complexes, which carry out the degradation of proteins and regulate diverse important biological processes. Anthers and pollen development have a huge importance in crop breeding. Despite the vast diversity of FBPs in Arabidopsis male reproductive organs, their role in anther and pollen development is not much explored. Moreover, a standard nomenclature for naming FBPs is also lacking. Here, we propose a standard nomenclature for naming the FBPs of Arabidopsis thaliana uniformly and carry out a systematic analysis of sperm cell-specific FBP gene, i.e., 3p.AtFBP113 due to its reported high and preferential expression, for detailed functional annotation. The results revealed that 3p.AtFBP113 is located on the small arm of chromosome and encodes 397 amino acid long soluble, stable, and hydrophilic protein with the possibility of localization in various cellular compartments. The presence of the C-terminal F-box associated domain (FBA) with immunoglobulin-like fold anticipated its role in protein binding. Gene ontology based functional annotation and tissue-specific gene co-expression analysis further strengthened its role in protein binding and ubiquitination. Moreover, various potential post/co-translational modifications were anticipated and the predicted tertiary structure also showed the presence of characteristic domains and fold. Thus, the outcomes of the study will be useful in developing a better understating of the function of 3p.AtFBP113 during the process of pollen development, which will be helpful for targeting the gene for manipulation of male fertility that has immense importance in hybrid breeding.

In vitro and in vivo evaluation of cephalosporins for the treatment of Lyme disease.

BACKGROUND: Lyme disease accounts for >90% of all vector-borne disease cases in the United States and affect ~300,000 persons annually in North America. Though traditional tetracycline antibiotic therapy is generally prescribed for Lyme disease, still 10%-20% of patients treated with current antibiotic therapy still show lingering symptoms. METHODS: In order to identify new drugs, we have evaluated four cephalosporins as a therapeutic alternative to commonly used antibiotics for the treatment of Lyme disease by using microdilution techniques like minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC). We have determined the MIC and MBC of four drugs for three Borrelia burgdorferi s.s strains namely CA8, JLB31 and NP40. The binding studies were performed using in silico analysis. RESULTS: The MIC order of the four drugs tested is cefoxitin (1.25 µM/mL) > cefamandole (2.5 µM/mL), > cefuroxime (5 µM/mL) > cefapirin (10 µM/mL). Among the drugs that are tested in this study using in vivo C3H/HeN mouse model, cefoxitin effectively kills B. burgdorferi. The in silico analysis revealed that all four cephalosporins studied binds effectively to B. burgdorferi proteins, SecA subunit penicillin-binding protein (PBP) and Outer surface protein E (OspE). CONCLUSION: Based on the data obtained, cefoxitin has shown high efficacy killing B. burgdorferi at concentration of 1.25 µM/mL. In addition to it, cefoxitin cleared B. burgdorferi infection in C3H/HeN mice model at 20 mg/kg.

Prediction of promiscuous T-cell epitopes in the Zika virus polyprotein: An in silico approach.

OBJECTIVE: To predict immunogenic promiscuous T cell epitopes from the polyprotein of the Zika virus using a range of bioinformatics tools. To date, no epitope data are available for the Zika virus in the IEDB database. METHODS: We retrieved nearly 54 full length polyprotein sequences of the Zika virus from the NCBI database belonging to different outbreaks. A consensus sequence was then used to predict the promiscuous T cell epitopes that bind MHC 1 and MHC II alleles using PorPred1 and ProPred immunoinformatic algorithms respectively. The antigenicity predicted score was also calculated for each predicted epitope using the VaxiJen 2.0 tool. RESULTS: By using ProPred1, 23 antigenic epitopes for HLA class I and 48 antigenic epitopes for HLA class II were predicted from the consensus polyprotein sequence of Zika virus. The greatest number of MHC class I binding epitopes were projected within the NS5 (21%), followed by Envelope (17%). For MHC class II, greatest number of predicted epitopes were in NS5 (19%) followed by the Envelope, NS1 and NS2 (17% each). A variety of epitopes with good binding affinity, promiscuity and antigenicity were predicted for both the HLA classes. CONCLUSION: The predicted conserved promiscuous T-cell epitopes examined in this study were reported for the first time and will contribute to the imminent design of Zika virus vaccine candidates, which will be able to induce a broad range of immune responses in a heterogeneous HLA population. However, our results can be verified and employed in future efficacious vaccine formulations only after successful experimental studies.

Identification of new drug candidates against Borrelia burgdorferi using high-throughput screening.

Lyme disease is the most common zoonotic bacterial disease in North America. It is estimated that >300,000 cases per annum are reported in USA alone. A total of 10%-20% of patients who have been treated with antibiotic therapy report the recrudescence of symptoms, such as muscle and joint pain, psychosocial and cognitive difficulties, and generalized fatigue. This condition is referred to as posttreatment Lyme disease syndrome. While there is no evidence for the presence of viable infectious organisms in individuals with posttreatment Lyme disease syndrome, some researchers found surviving Borrelia burgdorferi population in rodents and primates even after antibiotic treatment. Although such observations need more ratification, there is unmet need for developing the therapeutic agents that focus on removing the persisting bacterial form of B. burgdorferi in rodent and nonhuman primates. For this purpose, high-throughput screening was done using BacTiter-Glo assay for four compound libraries to identify candidates that stop the growth of B. burgdorferi in vitro. The four chemical libraries containing 4,366 compounds (80% Food and Drug Administration [FDA] approved) that were screened are Library of Pharmacologically Active Compounds (LOPAC1280), the National Institutes of Health Clinical Collection, the Microsource Spectrum, and the Biomol FDA. We subsequently identified 150 unique compounds, which inhibited >90% of B. burgdorferi growth at a concentration of <25 µM. These 150 unique compounds comprise many safe antibiotics, chemical compounds, and also small molecules from plant sources. Of the 150 unique compounds, 101 compounds are FDA approved. We selected the top 20 FDA-approved molecules based on safety and potency and studied their minimum inhibitory concentration and minimum bactericidal concentration. The promising safe FDA-approved candidates that show low minimum inhibitory concentration and minimum bactericidal concentration values can be chosen as lead molecules for further advanced studies.