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The current pandemic caused by the COVID-19 disease has reached everywhere in the world and has affected every aspect of our lives. As of the current data, the World Health Organization (WHO) has reported more than 300 million confirmed COVID-19 cases worldwide and more than 5 million deaths. M

COVID-19 was declared a pandemic by the World Health Organization (WHO) in March 2020. The disease is caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2). The aim of this study is to target the SARS-CoV-2 virus main protease (Mpro) via structure-based virtual screening. Consequently, > 580,000 ligands were processed via several filtration and docking steps, then the top 21 compounds were analysed extensively via MM-GBSA scoring and molecular dynamic simulations. Interestingly, the top compounds showed favorable binding energies and binding patterns to the protease enzyme, forming interactions with several key residues. Trihydroxychroman and pyrazolone derivatives, SN02 and SN18 ligands, exhibited very promising binding modes along with the best MM-GBSA scoring of –40.9 and –41.2 kcal mol−1, resp. MD simulations of 300 ns for the ligand-protein complexes of SN02 and SN18 affirmed the previously attained results of the potential inhibition activity of these two ligands. These potential inhibitors can be the starting point for further studies to pave way for the discovery of new antiviral drugs for SARS-CoV-2.

Despite available treatments, breast cancer is the leading cause of cancer-related death. Knowing that the tyrosine phosphatase SHP2 is a regulator in tumorigenesis, developing inhibitors of SHP2 in breast cells is crucial. Our study investigated the effects of new compounds, purchased from NSC, on the phosphatase activity of SHP2 and the modulation of breast cancer cell lines’ proliferation and viability. A combined ligand-based and structure-based virtual screening protocol was validated, then performed, against SHP2 active site. Top ranked compounds were tested via SHP2 enzymatic assay, followed by measuring IC50 values. Subsequently, hits were tested for their anti-breast cancer viability and proliferative activity. Our experiments identified three compounds 13030, 24198, and 57774 as SHP2 inhibitors, with IC50 values in micromolar levels and considerable selectivity over the analogous enzyme SHP1. Long MD simulations of 500 ns showed a very promising binding mode in the SHP2 catalytic pocket. Furthermore, these compounds significantly reduced MCF-7 breast cancer cells’ proliferation and viability. Interestingly, two of our hits can have acridine or phenoxazine cyclic system known to intercalate in ds DNA. Therefore, our novel approach led to the discovery of SHP2 inhibitors, which could act as a starting point in the future for clinically useful anticancer agents.

Patients infected with coronavirus have new experiences and hence new needs from the healthcare sector. Acknowledging patients’ experiences can exhibit promising outcomes in coronavirus management. Pharmacists are considered a vital pillar in managing patients’ experiences during their infection. A cross-sectional study was conducted to assess the experiences of COVID-19-infected individuals and the roles of pharmacists in the United Arab Emirates. The survey was face- and content-validated after being developed. Three sections were included in the survey (demographics, experiences of infected individuals, and the roles of pharmacists). Data were analyzed using the Statistical Package for the Social Sciences. The study participants (n = 509) had a mean age of 34.50 (SD = 11.93). The most reported symptoms among participants were fatigue (81.5%), fever (76.8%), headache (76.6%), dry cough (74.1%), muscle or joint pain (70.7%), and sore throat (68.6%). Vitamin C was the most used supplement (88.6%), followed by pain relievers (78.2%). Female gender was the only factor associated with symptom severity. About 79.0% agreed that the pharmacist played an important and effective role during their infection. The most reported symptom was fatigue, with females reporting more severe symptoms. The role of the pharmacist proved to be vital during this pandemic.

Bacterial infections present a serious challenge to healthcare practitioners due to the emergence of resistance to numerous conventional antibacterial drugs. Therefore, new bacterial targets and new antimicrobials are unmet medical needs. Rhodanine derivatives are known to possess potent antimicrobial activities. In this study, we determined the activity spectrum of a series of new rhodanine derivatives against representative Gram-positive and Gram-negative bacterial strains. Compounds 3a and 5a had the highest activity with minimum inhibitory concentrations in the range of 1.12 - 2.5 μg/mL. Transmission electron microscope results confirmed that activities against bacteria occurred via rupturing of the cell wall. Molecular modeling results suggested that rhodanine derivatives have the potential to irreversibly bind to the penicillin-binding protein (PBP) Ser62 residue in the active site. Thus, our results suggested that these rhodanine derivatives could be potential antibacterial drug candidates with strong activity against Gram-negative bacteria.

Quinoline analogues exhibited diversified biological activities depending on the structure type. A number of natural products with pyrano[3,2-c]quinolone structural motifs and patented chromenes were reported as promising cytotoxic agents. A molecular docking study was employed to investigate the binding and functional properties of 3-amino pyranoquinolinone 2a-c as anti-cancer agents. The three 3-amino pyranoquinolinone 2a-c showed an interesting ability to intercalate the DNA-topoisomerase complex and were able to obtain energetically favorable binding modes (−8.3 - −7.5 kcal/mol). Compound 2c containing butyl chain superiority over the other two compounds 2a-b which appeared to be involved in arene-H interactions with the two dG13 aromatic centers. The butyl chain also appeared to be immersed into a side subpocket formed by the side chains of Asn520 and Glu522 and the backbone amide of Arg503, Gly504, Lys505 and Ile506. Hence, the 3-amino pyranoquinolinone 2c used as starting material to prepare derivatives of pyrano[3,2-c]quinolone containing 1,2,4-triazine ring 4a-b which will enhance the anti-cancer activity. Pyrano[3,2-c]quinoline-2,5-diones 2a-c and 4a-b were evaluated in vitro on cell lines Ehrlich Ascites carcinoma cells (EAC), liver cancer cell line Hep-G2 and breast cancer cell line MCF-7 for the development of novel anticancer agents. The screening results revealed that compounds 4a-b were found most active candidates as anticancer agents.

The ɑ7 receptor is a member in the nicotinic acetylcholine receptor (nAChR) which has been implicated in several neurological disorders. Beside normal agonists and antagonists of α7 nAChRs, several studies revealed other types of molecules that are able to activate or deactivate ɑ7 receptors via allosteric binding; those are called positive allosteric modulators (PAMs) or negative allosteric modulators (NAMs), with the former having more pharmacological importance than the latter. Since both types of modulators are believed to bind to the same place in the intracavity of the transmembrane domain, it was important to differentiate between them in terms of structural features and their binding with the target receptor, and then use these specific characteristics as filters to discriminate PAMs from NAMS. To do that, modulators’ physicochemical properties were investigated using two databases of known PAMs or NAMs which were then used to elucidate a specific pharmacophore for each class. Interestingly, PAMs were found to be relatively larger and more polar compared to NAMs, which was observed to carry a positive charge with double the number of cases than PAMs. Furthermore. a pharmacophore for each class was developed and the best PAMs pharmacophore was successfully able to pass 94% of tested PAMs and to eliminate 71% of NAMs, while the best NAM pharmacophore was able to pass 82% of NAMs and to filter out 85% of PAMs. Docking these known modulators into the α7 nAChRs allosteric site identified several amino acids that are key for specifically binding PAMs compared to NAMs. Next, these findings were employed in virtual screening and then seeding experiments were conducted to validate the developed pharmacophores usage as filters prior to the final docking. Interestingly, the number of retrieved PAMs in the final docking list was improved by up to five-fold compared to the non-filtered protocol, which clearly indicates for the efficiency of our protocol to pick true PAMs over decoys. Hence, the pharmacophore-based filtering technique developed in this work can act as a valuable tool in the pursuit of new, potent PAM molecules as therapeutically useful modulators of the α7 nicotinic receptors.

Butyrylcholinesterase (BChE) plays an important role in the progression of the Alzheimer’s disease. In this study, we used a structure-based virtual screening (VS) approach to discover new BChE inhibitors. A ligand database was filtered and docked to the BChE protein using Glide program. The outcome from VS was filtered and the top ranked hits were thoroughly examined for their fitting into the protein active site. Consequently, the best 38 hits were selected for in vitro testing using Ellman’s method, and six of which showed inhibition activity for BChE. Interestingly, the most potent hit (Compound 4) exhibited inhibitory activity against the BChE enzyme in the low micromolar level with an IC50 value of 8.3 µM. Hits obtained from this work can act as a starting point for future SAR studies to discover new BChE inhibitors as anti-Alzheimer agents.

In this study, the acid chlorides of pyrazolo[3,4-d]pyrimidine compounds were prepared and reacted with a number of nucleophiles. The novel compounds were experimentally tested via enzyme assay and they showed cyclooxygenase-2 inhibition activity in the middle micro molar range (4b had a COX-1 IC50 of 26 µM and a COX-2 IC50 of 34 µM, 3b had a COX-1 IC50 of 19 µM and a COX-2 IC50 of 31 µM, 3a had a COX-2 IC50 of 42 µM). These compounds were analyzed via docking and were predicted to interact with some of the COX-2 key residues. Our best hit, 4d (COX-1 IC50 of 28 µM, COX-2 IC50 of 23 µM), appears to adopt similar binding modes to the standard COX-2 inhibitor, celecoxib, proposing room for possible selectivity. Additionally, the resultant novel compounds were tested in several in vivo assays. Four compounds 3a (COX-2 IC50 of 42 µM), 3d, 4d and 4f were notable for their anti-inflammatory activity that was comparable to that of the clinically available COX-2 inhibitor celecoxib. Interestingly, they showed greater potency than the famous non-steroidal anti-inflammatory drug, Diclofenac sodium. In summary, these novel pyrazolo[3,4-d]pyrimidine analogues showed interesting anti-inflammatory activity and could act as a starting point for future drugs.

The need for new antibacterial agents is increasingly becoming of great importance as bacterial resistance to current drugs is quickly spreading. Enoyl-acyl carrier protein reductases (FabI) are important enzymes for fatty acid biosynthesis in bacteria and other micro-organisms. In this project, we conducted structure-based virtual screening against the FabI enzyme, and accordingly, 37 compounds were selected for experimental testing. Interestingly, five compounds were able to demonstrate antimicrobial effect with variable inhibition activity against various strains of bacteria and fungi. Minimum inhibitory concentrations of the active compounds were determined and showed to be in low to medium micromolar range. Subsequently, enzyme inhibition assay was carried out for our five antimicrobial hits to confirm their biological target and determine their IC50 values. Three of these tested compounds exhibited inhibition activity for the FabI enzyme where our best hit MN02 had an IC50 value of 7.8 μM. Furthermore, MN02 is a small bisphenolic compound that is predicted to have all required features to firmly bind with the target enzyme. To sum up, hits discovered in this work can act as a good starting point for the future development of new and potent antimicrobial agents.

Protein tyrosine phosphatases (PTP) play important roles in the pathogenesis of many diseases. The fact that no PTP inhibitors have reached the market so far has raised many questions about their druggability. In this study, the active sites of 17 PTPs were characterized and assessed for its ability to bind drug-like molecules. Consequently, PTPs were classified according to their druggability scores into four main categories. Only four members showed intermediate to very druggable pocket; interestingly, the rest of them exhibited poor druggability. Particularly focusing on PTP1B, we also demonstrated the influence of several factors on the druggability of PTP active site. For instance, the open conformation showed better druggability than the closed conformation, while the tight-bound water molecules appeared to have minimal effect on the PTP1B druggability. Finally, the allosteric site of PTP1B was found to exhibit superior druggability compared to the catalytic pocket. This analysis can prove useful in the discovery of new PTP inhibitors by assisting researchers in predicting hit rates from high throughput or virtual screening and saving unnecessary cost, time, and efforts via prioritizing PTP targets according to their predicted druggability.

Noor Atatreh,1 Mohammad A Ghattas,1 Sanaa K Bardaweel,2 Sara Al Rawashdeh,1 Mohammad Al Sorkhy1 1Department of Pharmaceutical Sciences, College of Pharmacy, Al Ain University of Science and Technology, Al Ain, Abu Dhabi, United Arab Emirates; 2Department of Pharmaceutical Sciences, School of Pharmacy, The University of Jordan, Amman 11942, Jordan Background: The tumor suppressor protein p53 plays an important role in preventing tumor formation and progression through its involvement in cell division control and initiation of apoptosis. Mdm2 protein controls the activity of p53 protein through working as ubiquitin E3 ligase promoting p53 degradation through the proteasome degradation pathway. Inhibitors for Mdm2-p53 interaction have restored the activity of p53 protein and induced cancer fighting properties in the cell.Purpose: The objective of this study is to use computer-aided drug discovery techniques to search for new Mdm2-p53 interaction inhibitors.Methods: A set of pharmacophoric features were created based on a standard Mdm2 inhibitor and this was used to screen a commercial drug-like ligand library; then potential inhibitors were docked and ranked in a multi-step protocol using GLIDE. Top ranked ligands from docking were evaluated for their inhibition activity of Mdm2-p53 interaction using ELISA testing.Results: Several compounds showed inhibition activity at the submicromolar level, which is comparable to the standard inhibitor Nutlin-3a. Furthermore, the discovered inhibitors were evaluated for their anticancer activities against different breast cancer cell lines, and they showed an interesting inhibition pattern.Conclusion: The reported inhibitors can represent a starting point for further SAR studies in the future and can help in the discovery of new anticancer agents. Keywords: protein–protein interaction, virtual screening, Mdm2, p53, anticancer, docking, pharmacophore, ELISA

The presence of false positives in enzyme inhibition assays is a common problem in early drug discovery, especially for compounds that form colloid aggregates in solution. The molecular basis of these aggregates could not be thoroughly explored because of their transient stability. In this study we conducted comparative molecular dynamics (MD) simulations of miconazole, a strong aggregator, and fluconazole, a known non-aggregator. Interestingly, miconazole displays full aggregation within only 50ns, whilst fluconazole shows no aggregation over the 500ns simulation. The simulations indicate that the center of the aggregate is densely packed by the hydrophobic groups of miconazole, whereas polar and nonpolar groups comprise the surface to form a micelle-like colloid. The amphiphilic moment and planar nature of the miconazole structure appear to promote its aggregating behavior. The simulations also predict rapid aggregate formation for a second known promiscuous inhibitor, nicardipine. Thus, MD appears to be a useful tool to characterize aggregate-prone inhibitors at molecular-level detail and has the potential to provide useful information for drug discovery and formulation design.

Enoyl-acyl carrier protein reductases have an important role in fatty acid biosynthesis and are considered essential for bacterial and protozoal survival. Here, we perform a computational assessment of enoyl-acyl carrier protein reductase structures, providing insights for inhibitor design that we incorporate into a virtual screening approach. Firstly, we analyse 80 crystal structures of 16 different enoyl-acyl carrier protein reductases for their active site characteristics and druggability, finding these sites contain a readily druggable pocket, of varying size and shape. Interestingly, a high affinity, potentially allosteric site was identified for pfFabl. Analysis of the ligand-protein interactions of four enoyl-acyl carrier protein reductases from different micro-organisms (InhA, pfFabl, saFabl and ecFabl), involving 59 available crystal structures, found three commonly shared interactions; constraining these interactions in docking improved enrichment of enoyl-acyl carrier protein reductase virtual screens, by up to 60% in the top 3% of the ranked library. This docking protocol also improved pose prediction, decreasing the root-mean-square deviation to crystallographic pose by up to 75% on average. The binding site analysis and knowledge-based docking protocol presented here can potentially assist in the structure-based design of new enoyl-acyl carrier protein reductase inhibitors.

Effects of the histamine H₁ receptor (H1R) antagonists (antihistamines), promethazine (PMZ), orphenadrine (ORP), chlorpheniramine (CLP), pyrilamine (PYR), diphenhydramine (DPH), citerizine (CTZ), and triprolidine (TRP) on the functional properties of the cloned α7 subunit of the human nicotinic acetylcholine receptor expressed in Xenopus oocytes were investigated. Antihistamines inhibited the α7-nicotinic acetylcholine receptor in the order PYR>CLP>TRP>PMZ>ORP≥DPH≥CTZ. Among the antihistamines, PYR showed the highest reversible inhibition of acetylcholine (100 µM)-induced responses with IC₅₀ of 6.2 µM. PYR-induced inhibition was independent of the membrane potential and could not be reversed by increasing the concentration of acetylcholine. Specific binding of [¹²⁵I] α-bungarotoxin, a selective antagonist for α7-nicotinic acetylcholine receptor, was not changed in the presence of PYR suggesting a non-competitive inhibition of nicotinic receptors. In line with functional experiments, docking studies indicated that PYR can potentially bind allosterically with the α7 transmembrane domain. Our results indicate that the H₂-H₄ receptor antagonists tested in this study (10 µM) showed negligible inhibition of α7-nicotinic acetylcholine receptors. On the other hand, H₁ receptor antagonists inhibited the function of human α7-nicotinic acetylcholine receptor, with varying potencies. These results emphasize the importance of α7-nicotinic acetylcholine receptor for future pharmacological/toxicological profiling.

Docking-based virtual screening is an established component of structure-based drug discovery. Nevertheless, scoring and ranking of computationally docked ligand libraries still suffer from many false positives. Identifying optimal docking parameters for a target protein prior to virtual screening can improve experimental hit rates. Here, we examine protocols for virtual screening against the important but challenging class of drug target, protein tyrosine phosphatases. In this study, common interaction features were identified from analysis of protein-ligand binding geometries of more than 50 complexed phosphatase crystal structures. It was found that two interactions were consistently formed across all phosphatase inhibitors: (1) a polar contact with the conserved arginine residue, and (2) at least one interaction with the P-loop backbone amide. In order to investigate the significance of these features on phosphatase-ligand binding, a series of seeded virtual screening experiments were conducted on three phosphatase enzymes, PTP1B, Cdc25b and IF2. It was observed that when the conserved arginine and P-loop amide interactions were used as pharmacophoric constraints during docking, enrichment of the virtual screen significantly increased in the three studied phosphatases, by up to a factor of two in some cases. Additionally, the use of such pharmacophoric constraints considerably improved the ability of docking to predict the inhibitor's bound pose, decreasing RMSD to the crystallographic geometry by 43% on average. Constrained docking improved enrichment of screens against both open and closed conformations of PTP1B. Incorporation of an ordered water molecule in PTP1B screening was also found to generally improve enrichment. The knowledge-based computational strategies explored here can potentially inform structure-based design of new phosphatase inhibitors using docking-based virtual screening.

A new series of pyrimidine derivatives 5, 9a-d and 12a-d was synthesized by an efficient procedure. The antibacterial activity of the new compounds was studied against four bacterial strains. Compound 5 was found to exhibit the highest potency, with = 1.0 μg/ml, against both Escherichia coli and Pseudomonas aeruginosa when compared with amoxicillin (MIC = 1.0–1.5 μg/mL). Transmission electron microscope results confirmed that activities against bacteria occurred via rupturing of the cell wall. Molecular modeling results suggested that compounds 5, 9a-d and 12a-d have the potential to irreversibly bind to the penicillin-binding protein (PBP) Ser62 residue in the active site and were able to overcome amoxicillin resistance in bacteria by inhibiting the β-lactamase enzyme. Docking studies showed that compounds 5, 9a-d and 12a-d inhibit the β-lactamase enzyme through covalent bonding with Ser70. The synergistic effect with amoxicillin was studied. The newly synthesized compounds reported in this study warrant further consideration as prospective antimicrobial agents.

UCS 15A, an antibiotic produced by Streptomyces sp., has been reported to specifically disrupt SH3 domain-mediated interactions in eukaryotic cells. Interestingly, in the case of the non-receptor tyrosine kinase Src, UCS15A was effective in suppressing the SH3 domain-mediated intermolecular rather than intramolecular interactions, and thus prevented Src interactions with certain downstream effectors without affecting Src kinase activity. Here the synthesis of a novel difluoro analogue of UCS15A is described. The effects of this compound (8) on Src activity were tested in HCT 116 colorectal carcinoma cells engineered for inducible expression of c-Src. The presence of compound (8) resulted in the increased activity of the induced c-Src implicating that (8) acts as a c-Src activator in vivo. These observations are supported by computer modelling studies which suggest that the aldehyde group of (8) may covalently bind to a lysine residue in the SH2-kinase linker region situated in the proximity of the SH3 domain, which could promote a conformational change resulting in increased Src activity.

Src signalling and transduction are directly involved in cell growth, cell cycle, malignant transformation and cell migration, providing therapeutic opportunities through inhibition of Src. Here we report virtual screening for novel compounds that inhibit the Src-SH3 protein–protein interaction with a proline-rich peptide ligand. Computational docking of the ZINC compound database was performed using GOLD. Top-scoring compounds were assayed using a fluorescence polarization-based assay. A benzoquinoline derivative showed micromolar inhibition of binding between Src-SH3 and the proline-rich peptide. Several analogues were subsequently assayed showing the requirement of a linker between the benzoquinoline and phenyl rings, and electron donating substituents on the phenyl ring.

MDM2 is a protein that regulates the action of tumor suppressor protein P53. Inhibiting the interaction between the two proteins is widely considered in anti-cancer drug discovery approach. Targeting p53-bindig site on the MDM2 protein can be useful for the development of new anticancer agents. Several drugs with selective activity have been introduced to the market and are used for treatment of several types of cancers. In this study we explored the inhibition of MDM2 activity through studying 32 crystal structures of MDM2-ligand complexes downloaded from protein data bank (PDB). MDM2 protein structures were analyzed using protein-ligand interaction fingerprint to determine key residues for ligand binding. A 3D pharmacophore set was created and validated with a set of features that include aromatic and hydrophobic properties. Furthermore libraries of potential small lead-like ligands were screened on the pharmacophore. Ligands which pose three pharmacophoric features were carried to the next step where receptor-based virtual screening was performed using GLIDE docking software. The top 10% obtained from this screening were then redocked into the MDM2 binding site using more extensive search and scoring technique (GLIDE_XP) in order to enhance screening accuracy. The resultant top list was visually examined and compounds with best binding mode were selected for experimental testing. This virtual technique for discovering new lead-like MDM2 inhibitors will take into consideration several features that current inhibitors may lack such as solubility and bioavailability. Citation Format: Noor Atatreh, Ramez A. Mansour, Mohammad A. Ghattas. Molecular modeling approach for exploring the MDM2 active site for the discovery of new P53-MDM2 inhibitors. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr B45.

Protein tyrosine phosphatases play important roles in the signalling system in our bodies and were observed to be overexpressed in many diseases. For instance, PTP1B, the most famous member of this family, has a well-established role in diabetes mellitus, obesity and cancer. However, no PTP inhibitors have reached the market so far. This raised a question about the druggability of their catalytic site; which appears to be hydrophilic in nature and is believed to favour mainly polar ligands to bind with. In this study, we did an extensive data minding in the protein data bank to obtain all available crystal structures of all members in the PTP family. We analysed these crystal structures using SiteMap/Schrodinger. This software finds cavities in the examined proteins structure and evaluates these pockets according to their suitability for binding with drug-like ligands. Consequently, we classified PTPs according to their druggability scores; a representative of each category is shown and discussed accordingly. The influence of active site flexibility (open or closed) on PTPs druggability was studied. The effect of tight-bound water molecules on active site druggability was also assessed. This analysis can prove useful in the discovery of new PTP inhibitors and can help researchers to save unnecessary cost, money and efforts by prioritizing PTP targets according to which members have the most druggable catalytic pocket. Citation Format: Mohammad A. Ghattas, Noor Raslan, Asil Sadeq, Noor Atatreh. Druggability assessment of protein tyrosine phosphatase binding site. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr B44.

Purpose : To perform a virtual screening for a set of drug-like ligand library against the Staphylococcus aureus enoyl acyl carrier protein reductase, saFabI. Methods : The virtual screening was conducted based on a previously validated pharmacophoreconstrained docking. Consequently, the top list obtained was filtered using visual inspection where forty compounds were selected for experimental testing using disk-diffusion test and broth dilution method. The hits obtained were checked for their toxicity against human fibroblasts cell lines. Results: Three compounds were active against Staphylococcus aureus and other tested gram-positive bacteria. However, no significant inhibitory activity (p < 0.05) was detected against Escherichia coli or Candida albicans . The minimum inhibitory concentration (MIC) values for the most active compounds were identified using the broth dilution method; all of them exhibited inhibitory activity within micromolar range. The docking results showed that the hits obtained exhibited a small size with a nice binding mode to saFabI enzyme, forming the important interactions with the key residues. Furthermore, the best three hits demonstrated good safety profile as they did not show any significant toxicity against human fibroblast cell line. Conclusion : Overall, the newly discovered hits can act as a good starting point in the future for the development of safe and potent antibacterial agents. Keywords : Enoyl acyl carrier protein reductase, saFabI, Antibacterial agents, Docking, Constraint, Virtual screening Tropical Journal of Pharmaceutical