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The fields of agronomy and pesticides have assumed significant roles in contemporary society. Pesticides can have adverse effects on human health, both in the short and long term. We have conducted a comprehensive analysis of the various categories of pesticides, providing a thorough examination of their modes of operation, prevalence, and global utilization. A critical review of reported research has been conducted to investigate the carcinogenic effects of agricultural pesticide use on human health. The widespread utilization of malathion and parathion for pest management indicates that individual occupational choices significantly impact their exposure to these chemicals. Pesticides can cause neurological abnormalities, reproductive problems, respiratory irritations, ecological disturbance, and the emergence of pest resistance, among other sublethal consequences beyond their carcinogenicity (breast cancer, lymphomas, multiple myeloma, bladder cancer, and leukemia). Ultimately, there is an anticipation for a forthcoming surge in endeavors to mitigate the utilization of hazardous pesticides and the consequent peril they pose to human well-being and the ecosystem.

Background: Amyloid β (Aβ) fibril agglomeration is crucial in Alzheimer’s disease (AD) etiology, leading to significant harm to the central nervous system. Polyphenols have been investigated for their capacity to hinder Aβ agglomeration. Objective: This investigation aimed to assess the potential of Ajwa date palm (Phoenix dactylifera)-based bioactives in binding and disrupting resilient Aβ1-42 fibrils through in-silico studies. Methods: The primary phytochemicals present in date palms were subjected to molecular docking with three different conformers of Aβ1-42 and Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analysis. The stability of the system was assessed through molecular dynamics (MD) simulation. Results: It was noted that Diosmetin, Rutin, and Genistein effectively bind with 2BEG, 2MXU, and 2NAO fibrils, respectively, with docking energies ranging from −7.2 to −8.2 kcal/mol. Diosmetin, Rutin, and Genistein show notable pharmacokinetic variability, with LogP values from −1.69–2.58, with 1–6 rotatable bonds, and total polar surface areas (TPSA) between 112.52 and 240.90 Å2, characteristics important for drug candidacy evaluation. Their ADMET properties include solubility values of −3.238 to −3.595 mol/L, intestinal absorption of 23.4–93.4%, and VDss ranging from 0.094 to 1.663 L/kg. The ensuing MS simulations spanning 100 ns, illuminated the establishment of a robust peptide-chemical complex. Hydrophobic interactions, ionic and hydrogen bonds play a critical role in the ligand binding with their respective targets. Conclusions: These findings underscore the potential of these botanicals as leads for developing potent Aβ agglomeration inhibitors. However, before introducing into clinical settings, these findings need to be validated further.

Tumor-associated macrophages (TAMs) promote tumor advancement in many ways, such as inducing angiogenesis and the formation of new blood vessels that provide tumors with nourishment and oxygen. TAMs also facilitate tumor invasion and metastasis by secreting enzymes that degrade the extracellular matrix and generating pro-inflammatory cytokines that enhance the migration of tumor cells. TAMs also have a role in inhibiting the immune response against malignancies. To accomplish this, they release immunosuppressive cytokines such as IL-10, and TAMs can hinder the function of T cells and natural killer cells, which play crucial roles in the immune system's ability to combat cancer. The role of TAMs in breast cancer advancement is a complex and dynamic field of research. Therefore, TAMs are a highly favorable focus for innovative breast cancer treatments. This review presents an extensive overview of the correlation between TAMs and breast cancer development as well as its role in the tumor microenvironment (TME) shedding light on their impact on tumor advancement and immune evasion mechanisms. Notably, our study provides an innovative approach to employing nanomedicine approaches for targeted TAM therapy in breast cancer, providing an in-depth overview of recent advances in this emerging field.

Nanobiocatalysts (NBCs), which merge enzymes with nanomaterials, provide a potent method for improving enzyme durability, efficiency, and recyclability. This review highlights the use of eco-friendly synthesis methods to create sustainable nanomaterials for enzyme transport. We investigate different methods of immobilization, such as adsorption, ionic and covalent bonding, entrapment, and cross-linking, examining their pros and cons. The decreased environmental impact of green-synthesized nanomaterials from plants, bacteria, and fungi is emphasized. The review exhibits the various uses of NBCs in food industry, biofuel production, and bioremediation, showing how they can enhance effectiveness and eco-friendliness. Furthermore, we explore the potential impact of NBCs in biomedicine. In general, green nanobiocatalysts are a notable progression in enzyme technology, leading to environmentally-friendly and effective biocatalytic methods that have important impacts on industrial and biomedical fields.

Given the ongoing rise in the occurrence of allergic disorders, alterations in dietary patterns have been proposed as a possible factor contributing to the emergence and progression of these conditions. Currently, there is a significant focus on the development of dietary therapies that utilize natural compounds possessing anti-allergy properties. Dietary polyphenols and plant metabolites have been intensively researched due to their well-documented anti-inflammatory, antioxidant, and immunomodulatory characteristics, making them one of the most prominent natural bioactive chemicals. This study seeks to discuss the in-depth mechanisms by which these molecules may exert anti-allergic effects, namely through their capacity to diminish the allergenicity of proteins, modulate immune responses, and modify the composition of the gut microbiota. However, further investigation is required to fully understand these effects. This paper examines the existing evidence from experimental and clinical studies that supports the idea that different polyphenols, such as catechins, resveratrol, curcumin, quercetin, and others, can reduce allergic inflammation, relieve symptoms of food allergy, asthma, atopic dermatitis, and allergic rhinitis, and prevent the progression of the allergic immune response. In summary, dietary polyphenols and plant metabolites possess significant anti-allergic properties and can be utilized for developing both preventative and therapeutic strategies for targeting allergic conditions. The paper also discusses the constraints in investigating and broad usage of polyphenols, as well as potential avenues for future research.

Onosma bracteatum Wall (O. bracteatum) has been used traditionally for the management of arthritis; however, its therapeutic potential warrants further investigation. This study aimed to evaluate the anti-arthritic effects of the aqueous–ethanolic extract of O. bracteatum leaves (AeOB) in a rat model of complete Freund’s adjuvant (CFA)-induced arthritis. Rats were treated with AeOB (250, 500, and 750 mg/kg), indomethacin (10 mg/kg), or a vehicle control from days 8 to 28 post-CFA injection. Arthritic score, paw diameter, and body weight were monitored at regular intervals. X-ray radiographs and histopathological analysis were performed to assess arthritic severity. Inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP) were quantified by qPCR and icromatography. Phytochemical analysis of AeOB revealed alkaloids, flavonoids, phenols, tannins, Saponins, and glycosides. AeOB also exhibited antioxidant potential with an IC50 of 73.22 µg/mL in a DPPH assay. AeOB and diclofenac exhibited anti-inflammatory and anti-arthritic activities. Rats treated with AeOB at 750 mg/kg and indomethacin showed significantly reduced arthritic symptoms and joint inflammation versus the CFA control. The AeOB treatment downregulated TNF-α and IL-6 and decreased CRP levels compared with arthritic rats. Radiography and histopathology also showed improved prognosis. These findings demonstrate the anti-arthritic potential of AeOB leaves.

A pressure ulcer is defined as a skin lesion of ischemic origin, a condition that contributes to morbidity and mortality in patients with spinal cord injuries. The most common complication of ulcers is a bacterial infection. Antimicrobial therapy should be selected with caution for spinal cord injury patients since they have a high risk of developing multidrug-resistant (MDR) infections. The aim of this study was to determine the prevalence of different bacterial pathogens in patients with pressure ulcers admitted with spinal cord injuries. This was a retrospective single-center study that included adult patients aged 18 years and above, admitted with chronic pressure wounds after a spinal cord injury requiring hospitalization between 2015 and 2021. A total of 203 spinal cord injury patients with pressure ulcers were included in the study. Ulcers were commonly infected by Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli, and they were mostly located in the sacral and gluteal areas. More than half of the bacteria isolated from patients were sensitive to commonly tested antibiotics, while 10% were either MDR- or pan-drug-resistant organisms. Of the MDR bacterial isolates, 25.61% were methicillin-resistant S. aureus, and 17.73% were extended-spectrum beta-lactamase Enterobacteriaceae. The most prevalent bacteria in pressure ulcers of spinal cord injury patients were S. aureus. Other antibiotic-resistant organisms were also isolated from the wounds.

Antibiotics have revolutionized medicine, saving countless lives since their discovery in the early 20th century. However, the origin of antibiotics is now overshadowed by the alarming rise in antibiotic resistance. This global crisis stems from the relentless adaptability of microorganisms, driven by misuse and overuse of antibiotics. This article explores the origin of antibiotics and the subsequent emergence of antibiotic resistance. It delves into the mechanisms employed by bacteria to develop resistance, highlighting the dire consequences of drug resistance, including compromised patient care, increased mortality rates, and escalating healthcare costs. The article elucidates the latest strategies against drug-resistant microorganisms, encompassing innovative approaches such as phage therapy, CRISPR-Cas9 technology, and the exploration of natural compounds. Moreover, it examines the profound impact of antibiotic resistance on drug development, rendering the pursuit of new antibiotics economically challenging. The limitations and challenges in developing novel antibiotics are discussed, along with hurdles in the regulatory process that hinder progress in this critical field. Proposals for modifying the regulatory process to facilitate antibiotic development are presented. The withdrawal of major pharmaceutical firms from antibiotic research is examined, along with potential strategies to re-engage their interest. The article also outlines initiatives to overcome economic challenges and incentivize antibiotic development, emphasizing international collaborations and partnerships. Finally, the article sheds light on government-led initiatives against antibiotic resistance, with a specific focus on the Middle East. It discusses the proactive measures taken by governments in the region, such as Saudi Arabia and the United Arab Emirates, to combat this global threat. In the face of antibiotic resistance, a multifaceted approach is imperative. This article provides valuable insights into the complex landscape of antibiotic development, regulatory challenges, and collaborative efforts required to ensure a future where antibiotics remain effective tools in safeguarding public health.

Although, zinc oxide nanoparticles (ZRTs) as an anti-cancer agent have been the subject of numerous studies, none of the reports has investigated the impact of the reaction entry time of ion-carriers on the preparation of ZRTs. Therefore, we synthesized variants of ZRTs by extending the entry time of NaOH (that acts as a carrier of hydroxyl ions) in the reaction mixture. The anti-proliferative action, morphological changes, reactive oxygen species (ROS) production, and nuclear apoptosis of ZRTs on human A431 skin carcinoma cells were observed. The samples revealed crystallinity and purity by X-ray diffraction (XRD). Scanning electron microscopy (SEM) images of ZRT-1 (5 min ion carrier entry) and ZRT-2 (10 min ion carrier entry) revealed microtubule like morphology. On prolonging the entry time for ion carrier (NaOH) introduction in the reaction mixture, a relative ascent in the aspect ratio was seen. The typical ZnO band with a slight shift in the absorption maxima was evident with UV-visible spectroscopy. Both ZRT-1 and ZRT-2 exhibited non-toxic behavior as evident by RBC lysis assay. Additionally, ZRT-2 showed better anti-cancer potential against A431 cells as seen by MTT assay, ROS generation and chromatin condensation analyses. At 25 μM of ZRT-2, 5.56% cells were viable in MTT test, ROS production was enhanced to 166.71%, while 33.0% of apoptotic cells were observed. The IC50 for ZRT-2 was slightly lower (6 μM) than that for ZRT-1 (8 μM) against A431 cells. In conclusion, this paper presents a modest, economical procedure to generate ZRT nano-structures exhibiting strong cytotoxicity against the A431 cell line, indicating that ZRTs may have application in combating cancer.

In recent years, plant polyphenols have become a popular focus for the development of novel functional foods. Polyphenols, a class of bioactive compounds, including flavonoids, phenolic acids, and lignans, are commonly found in plant-based diets with a variety of biological actions, including antioxidant, anti-inflammatory, and anticancer effects. Unfortunately, polyphenols are not widely used in nutraceuticals since many of the chemicals in polyphenols possess poor oral bioavailability. Thankfully, polyphenols can be encapsulated and transported using bio-based nanocarriers, thereby increasing their bioavailability. Polyphenols’ limited water solubility and low bioavailability are limiting factors for their practical usage, but this issue can be resolved if suitable delivery vehicles are developed for encapsulating and delivering polyphenolic compounds. This paper provides an overview of the study of nanocarriers for the enhancement of polyphenol oral bioavailability, as well as a summary of the health advantages of polyphenols in the prevention and treatment of several diseases.

Anthocyanidins are the most abundant polyphenols in pomegranate juice. This class of molecules includes Delphinidin (Del), Cyanidin (Cya), and Pelargonidin (Pel). Using prostate, breast and pancreatic cancer cell lines PC3, MDA-MB-231, BxPC-3 and MiaPaCa-2, we show that anthocyanidins inhibit cell proliferation (measured by MTT assay) and induce apoptosis like cell death (measured by DNA/Histone ELISA). Copper chelator neocuproine and reactive oxygen species scavengers (thiourea for hydroxyl radical and superoxide dismutase for superoxide anion) significantly inhibit this reaction thus demonstrating that intracellular copper reacts with anthocyanidins in cancer cells to cause DNA damage via ROS generation. We further show that copper-supplemented media sensitizes normal breast epithelial cells (MCF-10A) to Del-mediated growth inhibition as determined by decreased cell proliferation. Copper supplementation results in increased expression of copper transporters Ctr1 and ATP7A in MCF-10A cells, which is attenuated by the addition of Del in the medium. We propose that the copper mediated, ROS-induced mechanism of selective cell death of cancer cells may in part explain the anticancer effects of anthocyanidins.

Cancer is a major cause of death worldwide, with multiple pathophysiological manifestations. In particular, genetic abnormalities, inflammation, bad eating habits, radiation exposure, work stress, and toxin consumption have been linked to cancer disease development and progression. Recently, natural bioactive chemicals known as polyphenols found in plants were shown to have anticancer capabilities, destroying altered or malignant cells without harming normal cells. Flavonoids have demonstrated antioxidant, antiviral, anticancer, and anti-inflammatory effects. Flavonoid type, bioavailability, and possible method of action determine these biological actions. These low-cost pharmaceutical components have significant biological activities and are beneficial for several chronic disorders, including cancer. Recent research has focused primarily on isolating, synthesizing, and studying the effects of flavonoids on human health. Here we have attempted to summarize our current knowledge of flavonoids, focusing on their mode of action to better understand their effects on cancer.

Cancer incidence varies around the globe, implying a relationship between food and cancer risk. Plant polyphenols are a class of secondary metabolites that have recently attracted attention as possible anticancer agents. The subclass of polyphenols, known as isoflavones, includes genistein and daidzein, which are present in soybeans and are regarded as potent chemopreventive agents. According to epidemiological studies, those who eat soy have a lower risk of developing certain cancers. Several mechanisms for the anticancer effects of isoflavones have been proposed, but none are conclusive. We show that isoflavones suppress prostate cancer cell growth by mobilizing endogenous copper. The copper-specific chelator neocuproine decreases the apoptotic potential of isoflavones, whereas the iron and zinc chelators desferroxamine mesylate and histidine do not, confirming the role of copper. Reactive oxygen species (ROS) scavengers reduce isoflavone-induced apoptosis in these cells, implying that ROS are cell death effectors. Our research also clearly shows that isoflavones interfere with the expression of the two copper transporter genes, CTR1 and ATP7A, in cancerous cells. Copper levels are widely known to be significantly raised in all malignancies, and we confirm that isoflavones can target endogenous copper, causing prooxidant signaling and, eventually, cell death. These results highlight the importance of copper dynamics within cancer cells and provide new insight into the potential of isoflavones as cancer-fighting nutraceuticals.

Bioassay-guided isolation from Camellia sinensis (Theaceae) and Colchicum luteum (Liliaceae) utilizing an in vitro model of protease assay revealed colchicine (1) and caffeine (2) from chloroform fractions, respectively. Their structures were validated using spectral techniques. The purified compounds were further optimized with Gaussian software utilizing the B3LYP functional and 6-31G(d,p) basis set. The result files were utilized to determine several global reactivity characteristics to explain the diverse behavior of the compounds. Colchicine (1) showed a higher inhibition of protease activity (63.7 ± 0.5 %age with IC50 = 0.83 ± 0.07 mM), compared with caffeine (2) (39.2 ± 1.3 %age). In order to determine the type of inhibition, compound 1 was further studied, and, based on Lineweaver–Burk/Dixon plots and their secondary replots, it was depicted that compound 1 was a non-competitive inhibitor of this enzyme, with a Ki value of 0.690 ± 0.09 mM. To elucidate the theoretical features of protease inhibition, molecular docking studies were performed against serine protease (PDB #1S0Q), which demonstrated that compound 1 had a strong interaction with the different amino acid residues located on the active site of this understudied enzyme, with a high docking score of 16.2 kcal/mol.

Moringa oleifera is rich in bioactive compounds such as beta-carotene, which have high nutritional values and antimicrobial applications. Several studies have confirmed that bioactive-compound-based herbal medicines extracted from the leaves, seeds, fruits and shoots of M. oleifera are vital to cure many diseases and infections, and for the healing of wounds. The β-carotene is a naturally occurring bioactive compound encoded by zeta-carotene desaturase (ZDS) and phytoene synthase (PSY) genes. In the current study, computational analyses were performed to identify and characterize ZDS and PSY genes retrieved from Arabidopsis thaliana (as reference) and these were compared with the corresponding genes in M. oleifera, Brassica napus, Brassica rapa, Brassica oleracea and Bixa orellana. The BLAST results revealed that all the plant species considered in this study encode β-carotene genes with 80–100% similarity. The Pfam analysis on β-carotene genes of all the investigated plants confirmed that they belong to the same protein family and domain. Similarly, phylogenetic analysis revealed that β-carotene genes of M. oleifera belong to the same ancestral class. Using the ZDS and PSY genes of Arabidopsis thaliana as a reference, we conducted qRT-PCR analysis on RNA extracted from the leaves of M. oleifera, Brassica napus, Brassica rapa and Bixa orellana. It was noted that the most significant gene expression occurred in the leaves of the studied medicinal plants. We concluded that not only are the leaves of M. oleifera an effective source of bioactive compounds including beta carotene, but also the leaves of Brassica napus, Brassica rapa and Bixa orellana can be employed as antibiotics and antioxidants against bacterial or microbial infections.

Heterocyclic compounds are considered as one of the major and most diverse family of organic compounds. Nowadays, the demand for these compounds is increasing day-by-day due to their enormous synthetic and biological applications. These heterocyclic compounds have unique antibacterial activity against various Gram-positive and Gram-negative bacterial strains. This review covers the antibacterial activity of different heterocyclic compounds with nitrogen moiety. Some of the derivatives of these compounds show excellent antibacterial activity, while others show reasonable activity against bacterial strains. This review paper aims to bring and discuss the detailed information on the antibacterial activity of various nitrogen-based heterocyclic compounds. It will be helpful for the future evolution of diseases to synthesize new and effective drug molecules.

Turmeric spice contains curcuminoids, which are polyphenolic compounds found in the Curcuma longa plant’s rhizome. This class of molecules includes curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Using prostate cancer cell lines PC3, LNCaP, DU145, and C42B, we show that curcuminoids inhibit cell proliferation (measured by MTT assay) and induce apoptosis-like cell death (measured by DNA/histone ELISA). A copper chelator (neocuproine) and reactive oxygen species scavengers (thiourea for hydroxyl radical, superoxide dismutase for superoxide anion, and catalase for hydrogen peroxide) significantly inhibit this reaction, thus demonstrating that intracellular copper reacts with curcuminoids in cancer cells to cause DNA damage via ROS generation. We further show that copper-supplemented media sensitize normal breast epithelial cells (MCF-10A) to curcumin-mediated growth inhibition, as determined by decreased cell proliferation. Copper supplementation results in increased expression of copper transporters CTR1 and ATP7A in MCF-10A cells, which is attenuated by the addition of curcumin in the medium. We propose that the copper-mediated, ROS-induced mechanism of selective cell death of cancer cells may in part explain the anticancer effects of curcuminoids.

l-Tryptophan derived Schiff base ligand and its complexes of the type, [ML(H2O)2]·H2O [M = Co(II), Ni(II), Zn(II)] and [CuL] have been synthesized and characterized on the basis of results obtained from elemental analysis, conductivity measurements, ESI-Mass spectral studies, FT-IR, 1H and 13C NMR, UV–Vis spectroscopy and magnetic moment data. The synthesized complexes were subjected to thermogravimetric analysis to study their decomposition pattern and stability. The fluorescence and viscosity measurements reveal that complexes have significant CT-DNA binding. However, upon comparing the DNA binding analyses, Cu(II) complex exhibited significant binding affinity. Keywords: l-Tryptophan based Schiff base complexes, Spectroscopic studies, DNA-binding

New Delhi metallo-β-lactamase-1 (NDM-1), expressed in different Gram-negative bacteria, is a versatile enzyme capable of hydrolyzing β-lactam rings containing antibiotics such as penicillins, cephalosporins, and even carbapenems. Multidrug resistance in bacteria mediated by NDM-1 is an emerging threat to the public health, with an enormous economic burden. There is a scarcity in the availability of specific NDM-1 inhibitors, and also a lag in the development of new inhibitors in pharmaceutical industries. In order to identify novel inhibitors of NDM-1, we screened a library of more than 20 million compounds, available at the MCULE purchasable database. Virtual screening led to the identification of six potential inhibitors, namely, MCULE-1996250788-0-2, MCULE-8777613195-0-12, MCULE-2896881895-0-14, MCULE-5843881524-0-3, MCULE-4937132985-0-1, and MCULE-7157846117-0-1. Furthermore, analyses by molecular docking and ADME properties showed that MCULE-8777613195-0-12 was the most suitable inhibitor against NDM-1. An analysis of the binding pose revealed that MCULE-8777613195-0-12 formed four hydrogen bonds with the catalytic residues of NDM-1 (His120, His122, His189, and Cys208) and interacted with other key residues. Molecular dynamics simulation and principal component analysis confirmed the stability of the NDM-1 and MCULE-8777613195-0-12 complex. The in vitro enzyme kinetics showed that the catalytic efficiency (i.e., kcat/Km) of NDM-1 on various antibiotics decreased significantly in the presence of MCULE-8777613195-0-12, due to poor catalytic proficiency (kcat) and affinity (Km). The IC50 value of MCULE-8777613195-0-12 (54.2 µM) was comparable to that of a known inhibitor, i.e., D-captopril (10.3 µM). In sum, MCULE-8777613195-0-12 may serve as a scaffold to further design/develop more potent inhibitors of NDM-1 and other β-lactamases.

The possible roles of elevated endogenous copper levels in malignant cells are becoming increasingly understood at a greater depth. Our laboratory has previously demonstrated that tea catechins have the ability to mobilize endogenous copper and undergo a Fenton-like reaction that can selectively damage cancer cells. In this communication, by using a diverse panel of malignant cell lines, we demonstrate that the ability of the catechin family [(−)-epigallocatechin-3-gallate (EGCG), (−)-epigallocatechin (EGC), (−)-epicatechin (EC), and (+)-catechin (C)] to induce apoptosis is dependent on their structure. We further confirm that reactive oxygen species (ROS) are the terminal effectors causing copper-mediated DNA damage. Our studies demonstrate the role of cellular copper transporters CTR1 and ATP7A in the survival dynamics of malignant cells post-EGCG exposure. The results, when considered together with our previous studies, highlight the critical role that copper dynamics and mobilization plays in cancer cells and paves the way for a better understanding of catechins as nutraceutical supplements for malignancies.

Bacteria expressing New Delhi metallo-β-lactamase-1 (NDM-1) can hydrolyze β-lactam antibiotics (penicillins, cephalosporins, and carbapenems) and, thus, mediate multidrug resistance. The worldwide dissemination of NDM-1 poses a serious threat to public health, imposing a huge economic burden in the development of new antibiotics. Thus, there is an urgent need for the identification of novel NDM-1 inhibitors from a pool of already-known drug molecules. Here, we screened a library of FDA-approved drugs to identify novel non-β-lactam ring-containing inhibitors of NDM-1 by applying computational as well as in vitro experimental approaches. Different steps of high-throughput virtual screening, molecular docking, molecular dynamics simulation, and enzyme kinetics were performed to identify risedronate and methotrexate as the inhibitors with the most potential. The molecular mechanics/generalized Born surface area (MM/GBSA) and molecular dynamics (MD) simulations showed that both of the compounds (risedronate and methotrexate) formed a stable complex with NDM-1. Furthermore, analyses of the binding pose revealed that risedronate formed two hydrogen bonds and three electrostatic interactions with the catalytic residues of NDM-1. Similarly, methotrexate formed four hydrogen bonds and one electrostatic interaction with NDM-1’s active site residues. The docking scores of risedronate and methotrexate for NDM-1 were –10.543 kcal mol−1 and −10.189 kcal mol−1, respectively. Steady-state enzyme kinetics in the presence of risedronate and methotrexate showed a decreased catalytic efficiency (i.e., kcat/Km) of NDM-1 on various antibiotics, owing to poor catalytic proficiency and affinity. The results were further validated by determining the MICs of imipenem and meropenem in the presence of risedronate and methotrexate. The IC50 values of the identified inhibitors were in the micromolar range. The findings of this study should be helpful in further characterizing the potential of risedronate and methotrexate to treat bacterial infections.

The high risk of morbidity and mortality associated with SARS-CoV-2 has accelerated the development of many potential vaccines. However, these vaccines are designed against SARS-CoV-2 isolated in Wuhan, China, and thereby may not be effective against other SARS-CoV-2 variants such as the United Kingdom variant (VUI-202012/01). The UK SARS-CoV-2 variant possesses D614G mutation in the Spike protein, which impart it a high rate of infection. Therefore, newer strategies are warranted to design novel vaccines and drug candidates specifically designed against the mutated forms of SARS-CoV-2. One such strategy is to target ACE2 (angiotensin-converting enzyme2)–Spike protein RBD (receptor binding domain) interaction. Here, we generated a homology model of Spike protein RBD of SARS-CoV-2 UK strain and screened a marine seaweed database employing different computational approaches. On the basis of high-throughput virtual screening, standard precision, and extra precision molecular docking, we identified BE011 (Dieckol) as the most potent compounds against RBD. However, Dieckol did not display drug-like properties, and thus different derivatives of it were generated in silico and evaluated for binding potential and drug-like properties. One Dieckol derivative (DK07) displayed good binding affinity for RBD along with acceptable physicochemical, pharmacokinetic, drug-likeness, and ADMET properties. Analysis of the RBD–DK07 interaction suggested the formation of hydrogen bonds, electrostatic interactions, and hydrophobic interactions with key residues mediating the ACE2–RBD interaction. Molecular dynamics simulation confirmed the stability of the RBD–DK07 complex. Free energy calculations suggested the primary role of electrostatic and Van der Waals’ interaction in stabilizing the RBD–DK07 complex. Thus, DK07 may be developed as a potential inhibitor of the RBD–ACE2 interaction. However, these results warrant further validation by in vitro and in vivo studies.