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Abstract An opportunistic human pathogenic bacterium, Chromobacterium violaceum resists the potency of most antibiotics by exploiting the quorum sensing system within their community to control virulence factor expression. Therefore, blocking the quorum sensing mechanism could help to treat several infectious caused by this organism. The quorum sensing receptor (CviR) of C. violaceum was used as a model target in the current investigation to identify potentially novel quorum sensing inhibitors from Cladosporium spp. through in silico computational approaches. The molecular docking results confirmed the anti-quorum sensing potential of bioactive compounds from Cladosporium spp. through binding to CviR with varying docking scores between – 5.2 and – 9.5 kcal/mol. Relative to the positive control [Azithromycin (– 7.4 kcal/mol)], the top six metabolites of Cladosporium spp. had higher docking scores and were generally greater than – 8.5 kcal/mol. The thermodynamic stability and binding affinity refinement of top-ranked CviR inhibitors were further studied through a 160 ns molecular dynamic (MD) simulation. The Post-MD simulation analysis confirmed the top-ranked compounds' affinity, stability, and biomolecular interactions with CviR at 50 ns, 100 ns, and 160 ns with Coniochaetone K of the Cladosporium spp. having the highest binding free energy (– 30.87 kcal/mol) and best interactions (two consistent hydrogen bond contact) following the 160 ns simulation. The predicted pharmacokinetics properties of top selected compounds point to their drug likeliness, potentiating their chance as a possible drug candidate. Overall, the top-ranked compounds from Cladosporium spp., especially Coniochaetone K, could be identified as potential C. violaceum CviR inhibitors. The development of these compounds as broad-spectrum antibacterial medicines is thus possible in the future following the completion of further preclinical and clinical research.

Abstract Cladosporium spp. have been reported for their great diversity of secondary metabolites which represent as a prominent base material for verifying the biological activities. Several bioactive compounds which have antimicrobial, cytotoxic, quorum sensing inhibitory and phytotoxic activities have been isolated from Cladosporium species. Most of them are still needed to be explored for their anticancer properties. Therefore, the present study is focused on screening and identifying the bioactive compounds of Cladosporium spp. for their anticancer activity via the integrated approaches of Molecular Docking (MD), Molecular Dynamics Simulation (MDS) and Density Functional Theory (DFT) studies. A total of 123 bioactive compounds of Cladosporium spp. were explored for their binding affinity with the selected breast cancer drug target receptor such as estrogen receptor alpha (PDB:6CBZ). The Molecular Docking studies revealed that amongst the bioactive compounds screened, Altertoxin X and Cladosporol H showed a good binding affinity of − 10.5 kcal/mol and − 10.3 kcal/mol, respectively, with the estrogen receptor alpha when compared to the reference compound (17 $$\upbeta$$ β -Estradiol: − 10.2 kcal/mol). The MDS study indicated the stable binding patterns and conformation of the estrogen receptor alpha-Altertoxin X complex in a stimulating environment. In addition, in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) study suggested that Altertoxin X has a good oral bioavailability with a high LD $$_{50}$$ 50 value of 2.375 mol/kg and did not cause any hepatotoxicity and skin sensitization. In summary, the integrated approaches revealed that Altertoxin X possesses a promising anticancer activity and could serve as a new therapeutic drug for breast cancer treatment.

Abstract Plants are endowed with a large pool of structurally diverse small molecules known as secondary metabolites. The present study aims to virtually screen these plant secondary metabolites (PSM) for their possible anti-SARS-CoV-2 properties targeting four proteins/ enzymes which govern viral pathogenesis. Results of molecular docking with 4,704 ligands against four target proteins, and data analysis revealed a unique pattern of structurally similar PSM interacting with the target proteins. Among the top-ranked PSM which recorded lower binding energy (BE), > 50% were triterpenoids which interacted strongly with viral spike protein—receptor binding domain, > 32% molecules which showed better interaction with the active site of human transmembrane serine protease were belongs to flavonoids and their glycosides, > 16% of flavonol glycosides and > 16% anthocyanidins recorded lower BE against active site of viral main protease and > 13% flavonol glycoside strongly interacted with active site of viral RNA-dependent RNA polymerase. The primary concern about these PSM is their bioavailability. However, several PSM recorded higher bioavailability score and found fulfilling most of the drug-likeness characters as per Lipinski's rule (Coagulin K, Kamalachalcone C, Ginkgetin, Isoginkgetin, 3,3′-Biplumbagin, Chrysophanein, Aromoline, etc.). Natural occurrence, bio-transformation, bioavailability of selected PSM and their interaction with the target site of selected proteins were discussed in detail. Present study provides a platform for researchers to explore the possible use of selected PSM to prevent/ cure the COVID-19 by subjecting them for thorough in vitro and in vivo evaluation for the capabilities to interfering with the process of viral host cell recognition, entry and replication.

Breast cancer is the second most common malignancy in females worldwide and poses a great challenge that necessitates the identification of novel therapeutic agents from several sources. This research aimed to study the molecular docking and molecular dynamics simulations of four proteins (such as PDB: 6CBZ, 1FDW, 5GWK and 2WTT) with the selected phytochemicals from Withania somnifera to identify the potential inhibitors for breast cancer. The molecular docking result showed that among 44 compounds, two of them, Ashwagandhanolide and Withanolide sulfoxide have the potential to inhibit estrogen receptor alpha (ERα), 17-beta-hydroxysteroid -dehydrogenase type 1 (17β-HSD1), topoisomerase II alpha (TOP2A) and p73 tetramerization domain that are expressed during breast cancer. The molecular dynamics (MD) simulations results suggested that Ashwagandhanolide remained inside the binding cavity of four targeted proteins and contributed favorably towards forming a stable protein-ligand complex throughout the simulation. Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) properties confirmed that Ashwagandhanolide is hydrophobic and has moderate intestinal permeability, good intestinal absorption, and poor skin permeability. The compound has a relatively low VDss value (-1.652) and can be transported across ABC transporter and good central nervous system (CNS) permeability but did not easily cross the blood-brain barrier (BBB). This compound does not possess any mutagenicity, hepatotoxicity and skin sensitization. Based on the results obtained, the present study highlights the anticancer potential of Ashwagandhanolide, a compound from W. somnifera. Furthermore, in vitro and in vivo studies are necessary to perform before clinical trials to prove the potentiality of Ashwagandhanolide.

In the present study, the binding affinity of 52 bioactive secondary metabolites from Wedelia trilobata towards the anti-apoptotic B-cell lymphoma-2 (Bcl-2) protein (PDB: 2W3L) structure was identified by using in silico molecular docking and molecular dynamics simulation. The molecular docking results demonstrated that the binding energies of docked compounds with Bcl-2 protein ranged from −5.3 kcal/mol to −10.1 kcal/mol. However, the lowest binding energy (−10.1 kcal/mol) was offered by Friedelin against Bcl-2 protein when compared to other metabolites and the standard drug Obatoclax (−8.4 kcal/mol). The molecular dynamics simulations revealed that the Friedelin-Bcl-2 protein complex was found to be stable throughout the simulation period of 100 ns. Overall, the predicted Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) properties of Friedelin are relatively better than Obatoclax, with the most noticeable differences in many parameters where Friedelin has no AMES toxicity, hepatotoxicity, and skin sensitization. The ADMET profiling of selected compounds supported their in silico drug-likeness properties. Based on the computational analyses, the present study concluded that Friedelin of W. trilobata was found to be the potential inhibitor of the Bcl-2 protein, which merits attention for further in vitro and in vivo studies before clinical trials.

The ever-expanding pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has gained attention as COVID-19 and caused an emergency in public health to an unmatched level to date. However, the treatments used are the only options; currently, no effective and licensed medications are available to combat disease transmission, necessitating further research. In the present study, an in silico-based virtual screening of anti-HIV bioactive compounds from medicinal plants was carried out through molecular docking against the main protease (Mpro) (PDB: 6LU7) of SARS-CoV-2, which is a key enzyme responsible for virus replication. A total of 16 anti-HIV compounds were found to have a binding affinity greater than −8.9 kcal/mol out of 150 compounds screened. Pseudohypericin had a high affinity with the energy of −10.2 kcal/mol, demonstrating amino acid residual interactions with LEU141, GLU166, ARG188, and GLN192, followed by Hypericin (−10.1 kcal/mol). Moreover, the ADME (Absorption, Distribution, Metabolism and Excretion) analysis of Pseudohypericin and Hypericin recorded a low bioavailability (BA) score of 0.17 and violated Lipinski’s rule of drug-likeness. The docking and molecular simulations indicated that the quinone compound, Pseudohypericin, could be tested in vitro and in vivo as potent molecules against COVID-19 disease prior to clinical trials.This was also supported by the theoretical and computational studies conducted. The global and local descriptors, which are the underpinnings of Conceptual Density FunctionalTheory (CDFT) have beenpredicted through successful model chemistry, hoping that they could be of help in the comprehension of the chemical reactivity properties of the molecular systems considered in this study.

Agriculture has a lot of responsibility as the rise in the world’s population demands more food requirements. However, more than one type of biotic and abiotic stress continually impacts agricultural productivity. Drought stress is a major abiotic stress that significantly affects agricultural productivity every year as the plants undergo several morphological, biochemical, and physiological modifications, such as repressed root and shoot growth, reduced photosynthesis and transpiration rate, excessive production of reactive oxygen species (ROS), osmotic adjustments, and modified leaf senescence regulating and stress signaling pathways. Such modifications may permanently damage the plants; therefore, mitigation strategies must be developed. The use of drought resistant crop cultivars is more expensive and labor-intensive with few advantages. However, exploiting plant growth promoting rhizobacteria (PGPR) is a proven alternative with numerous direct and indirect advantages. The PGPR confers induced systemic tolerance (IST) mechanisms in plants in response to drought stress via multiple mechanisms, including the alteration of root architecture, maintenance of high relative water content, improvement of photosynthesis rate, production of phytohormones, exopolysaccharides, ACC deaminase, carotenoids and volatiles, induction of antioxidant defense system, and alteration in stress-responsive gene expression. The commercial application of PGPR as bioinoculants or biostimulants will remain contingent on more robust strain selection and performance under unfavorable environmental conditions. This review highlights the possible mechanisms of PGPR by activating the plant adaptive defense systems for enhancing drought tolerance and improving overall growth and yield.

Rhizosphere-resident fungi that are helpful to plants are generally termed as ‘plant growth promoting fungi’ (PGPF). These fungi are one of the chief sources of the biotic inducers known to give their host plants numerous advantages, and they play a vital role in sustainable agriculture. Today’s biggest challenge is to satisfy the rising demand for crop protection and crop yield without harming the natural ecosystem. Nowadays, PGPF has become an eco-friendly way to improve crop yield by enhancing seed germination, shoot and root growth, chlorophyll production, and fruit yield, etc., either directly or indirectly. The mode of action of these PGPF includes the solubilization and mineralization of the essential micro- and macronutrients needed by plants to regulate the balance for various plant processes. PGPF produce defense-related enzymes, defensive/volatile compounds, and phytohormones that control pathogenic microbes’ growth, thereby assisting the plants in facing various biotic and abiotic stresses. Therefore, this review presents a holistic view of PGPF as efficient natural biofertilizers to improve crop plants’ growth and resistance.

The study was undertaken to investigate the antioxidant, genotoxic, and cytotoxic potentialities of phyto-fabricated zinc oxide nanoparticles (ZnO-NPs) from Ipomoea obscura (L.) Ker Gawl. aqueous leaf extract. The UV-visible spectral analysis of the ZnO-NPs showed an absorption peak at 304 nm with a bandgap energy of 3.54 eV, which are characteristics of zinc nanoparticles. Moreover, the particles were of nano-size (~24.26 nm) with 88.11% purity and were agglomerated as observed through Scanning Electron Microscopy (SEM). The phyto-fabricated ZnO-NPs offered radical scavenging activity (RSA) in a dose-dependent manner with an IC50 of 0.45 mg mL−1. In addition, the genotoxicity studies of ZnO-NPs carried out on onion root tips revealed that the particles were able to significantly inhibit the cell division at the mitotic stage with a mitotic index of 39.49%. Further, the cytotoxic studies on HT-29 cells showed that the phyto-fabricated ZnO-NPs could arrest the cell division as early as in the G0/G1 phase (with 92.14%) with 73.14% cells showing early apoptotic symptoms after 24 h of incubation. The results of the study affirm the ability of phyto-fabricated ZnO-NPs from aqueous leaf extract of I. obscura is beneficial in the cytotoxic application.

Cinnamomum verum plant extract mediated propellant chemistry route was used for the green synthesis of zinc oxide nanoparticles. Prepared samples were confirmed for their nano regime using advanced characterization techniques such as powder X-ray diffraction and microscopic techniques such as scanning electron microscopy and transmission electron microscopy. The energy band gap of the green synthesized zinc oxide (ZnO)-nanoparticles (NPs) were found between 3.25−3.28 eV. Fourier transmission infrared spectroscopy shows the presence of Zn-O bond within the wave number of 500 cm−1. SEM images show the specific agglomeration of particles which was also confirmed by TEM studies. The green synthesized ZnO-NPs inhibited the growth of Escherichia coli and Staphylococcus aureus with a minimum inhibitory concentration (MIC) of 125 µg mL−1 and 62.5 µg mL−1, respectively. The results indicate the prepared ZnO-NPs can be used as a potential antimicrobial agent against harmful pathogens.