Severe Acute Respiratory Syndrome Corona Virus (SARS-CoV-2) is the causative agent of COVID-19 pandemic, which has resulted in global fatalities since late December 2019. Alkaloids play a significant role in drug design for various antiviral diseases, which makes them viable candidates for treating COVID-19. To identify potential antiviral agents, 102 known alkaloids were subjected to docking studies against the two key targets of SARS-CoV-2, namely the spike glycoprotein and main protease. The spike glycoprotein is vital for mediating viral entry into host cells, and main protease plays a crucial role in viral replication; therefore, they serve as compelling targets for therapeutic intervention in combating the disease. From the selection of alkaloids, the top 6 dual inhibitory compounds, namely liensinine, neferine, isoliensinine, fangchinoline, emetine, and acrimarine F, emerged as lead compounds with favorable docked scores. Interestingly, most of them shared the bisbenzylisoquinoline alkaloid framework and belong to Nelumbo nucifera, commonly known as the lotus plant. Docking analysis was conducted by considering the key active site residues of the selected proteins. The stability of the top three ligands with the receptor proteins was further validated through dynamic simulation analysis. The leads underwent ADMET profiling, bioactivity score analysis, and evaluation of drug-likeness and physicochemical properties. Neferine demonstrated a particularly strong affinity for binding, with a docking score of -7.5025 kcal/mol for main protease and -10.0245 kcal/mol for spike glycoprotein, and therefore a strong interaction with both target proteins. Of the lead alkaloids, emetine and fangchinoline demonstrated the lowest toxicity and high LD50 values. These top alkaloids, may support the body’s defense and reduce the symptoms by their numerous biological potentials, even though some properties naturally point to their direct antiviral nature. These findings demonstrate the promising anti-COVID-19 properties of the six selected alkaloids, making them potential candidates for drug design. This study will be beneficial in effective drug discovery and design against COVID-19 with negligible side effects.

Tuberculosis (TB), an infectious disease caused by multi-drug resistant Mycobacterium tuberculosis (Mtb), has been a global health concern. Mtb affects over a third of the world’s population, causing two million deaths annually due to its dormancy and propensity to spread infection during this period. Resuscitation-promoting factor B (RpfB) plays a pivotal role in the growth of Mtb during dormant periods, making it a critical target for eliminating Mtb and curing TB. Gymnema sylvestre is a famous medicinal plant with several medicinal properties, including antimicrobial activity; however, the therapeutic potential of the various reported metabolites of this plant against Mtb has not yet been explored. The aim of this study was to explore the reported natural products of G. sylvestre against the RpfB of the Mtb. A total of 131 reported secondary metabolites of this plant were collected and virtually screened against the RpfB. We particularly targeted the Glu292 residue of RpfB as it is crucial for the catalysis of this protein. From our in-house library, 114 compounds showed a binding affinity higher than the standard drug. The binding stability of the top three lead compounds was further confirmed through MD simulation analysis. Drug likeness analyses indicated that the ten hits had zero violations of the Lipinski rule of five. In addition, analyses of pharmacokinetics, toxicity, and target prediction revealed that the top compounds are devoid of toxicity and do not affect human proteins. Additionally, they reflect multifaceted approach as anti-TB agents. Our selected hits not only exhibit molecular properties favoring physiological compatibility but also exhibit properties enhancing their potential efficacy as therapeutic candidates. The compounds investigated here are worthy of experimental validation for the discovery of novel treatments against TB. Further, this study also provides a promising avenue for research on the pharmacological potential of G. sylvestre.

Nonlinear optics (NLO) is a fascinating field that explores how intense light interacts with matter. Organic chromophores are regarded as promising materials for nonlinear optics research due to their properties i.e., easy of process, structural versatility, and instant response to NLO effects. Therefore, in current research, a comprehensive investigation was carried out on a series of organic indacenothienothiophene (ITT) based chromophores (AOR and AO1-AO6) to explore their NLO properties through quantum chemical calculations. The DFT and TD-DFT methods at M06/6-311G(d,p) level were employed to investigate the optoelectronic properties of new designed compounds. The parent compound, i.e., AOIC was taken for the designing of the reference molecule (AOR) by substituting one terminal acceptor with donor in AOIC to develop push–pull architecture. The other derivatives (AO1-AO6) were designed via modulation of end-capped acceptor of AOR with benzothiophene (BT) based acceptors. These investigations revealed a red-shift absorption spectra (λ_max = 783–848 nm) with reduced HOMO–LUMO energy gap (E_gap = 1.741–1.956 eV) in AO1-AO6 as compared to AOR (E_gap = 2.040; λ_max=743 nm) in chloroform. Significant charge transferred from donor to BT acceptors through ITT core in AO1-AO6 as illustrated by DOS, FMOs and TDM analyses. All entitled compounds (AO1-AO6) exhibited a notable NLO response relative to the AOR. Particularly, AO2 displayed the prominent results like < α > = 2.790 × 10^–22 esu, β_total = 7.027 × 10^–27 esu and γ_total = 11.440 × 10^–32 esu among all the derivatives. This might be owing to unique optoelectronic characteristics such as lowest E_gap (1.741 eV) and hardness (0.871 eV) with highest softness (0.574 eV) and absorption spectrum (820 nm) of AO2. Hence, these calculations illustrated that the end-capped substitution of acceptor moieties with BT acceptors and the incorporation of conjugated donor system played a vital role in improving the NLO aptitude. Overall, these ITT-based derivatives can be considered as potential materials for promising applications in NLO field.

Hydrogen peroxide (H₂O₂) is one of the main byproducts of most enzymatic reactions, and its detection is very important in disease conditions. Due to its essential role in healthcare, the food industry, and environmental research, accurate H₂O₂ determination is a prerequisite. In the present work, Morus nigra sawdust deposited zinc oxide (ZnO) nanoparticles (NPs) were synthesized by the use of Trigonella foenum extract via a hydrothermal process. The synthesized platform was characterized by various techniques, including UV-Vis, FTIR, XRD, SEM, EDX, etc. FTIR confirmed the presence of a Zn‒O characteristic peak, and XRD showed the hexagonal phase of ZnO NPs with a 35 nm particle size. The EDX analysis confirmed the presence of Zn and O. SEM images showed that the as-prepared nanoparticles are distributed uniformly on the surface of sawdust. The proposed platform (acetic acid-capped ZnO NPs deposited sawdust) functions as a mimic enzyme for the detection of H₂O₂ in the presence of 3,3′,5,5′-tetramethylbenzidine (TMB) colorimetrically. To get the best results, many key parameters, such as the amount of sawdust-deposited nanoparticles, TMB concentration, pH, and incubation time were optimized. With a linear range of 0.001–0.360 μM and an R² value of 0.999, the proposed biosensor’s 0.81 nM limit of quantification (LOQ) and 0.24 nM limit of detection (LOD) were predicted, respectively. The best response for the proposed biosensor was observed at pH 7, room temperature, and 5 min of incubation time. The acetic acid-capped sawdust deposited ZnO NPs biosensor was also used to detect H₂O₂ in blood serum samples of diabetic patients and suggest a suitable candidate for in vitro diagnostics and commercial purposes.

New Delhi metallo-beta-lactamase-1 (NDM-1) is a protein produced by bacteria carrying the blaNDM-1 gene, leading to antibiotic resistance, a major global health issue. NDM-1 hydrolyzes nearly all beta-lactam antibiotics, including last-resort carbapenems. Developing effective NDM-1 inhibitors is crucial, as none are currently available for clinical use. This study investigates the potential anti-NDM-1 effects of reported marine fungi-derived metabolites. Two hundred metabolites of fungal origin with antibacterial activity were collected and virtually screened targeting key active site residues of NDM-1. We examined the drug-likeness characteristics, interaction profile, and pharmacophoric features of the shortlisted metabolites followed by molecular dynamic (MD) simulation: RMSF, RMSD, Rg, SASA, hydrogen bond analysis, MMGBSA, PCA, and FEL. Fifty-eight metabolites exhibited greater binding affinity than the reference drug (meropenem) with the highest score of -6.59 kcal/mol. The top 7 metabolites were selected for interaction analysis based on drug-likeness criteria. The diverse interactions of our top metabolites with key residues (HIS-122, GLN-123, GLU-152, and ASN-220) suggest potential NDM-1 inhibition and disruption of bacterial resistance. Pharmacophoric features highlighted the effective structural characteristics of the top 3 metabolites. Three metabolites namely, 8-O-4-dehydrodiferulic acid, Emerixanthone B, and Trichaspside B demonstrated favorable dynamic behavior and binding stability, with 8-O-4-dehydrodiferulic acid showing the most promising potential. Furthermore, the top metabolites are non-toxic, compatible with β-lactam antibiotics, and show no predicted interactions with human proteins. These selected compounds exhibit favorable physiological compatibility and molecular characteristics that enhance their potential as therapeutic candidates. Given the urgent need for novel treatments targeting NDM-1, the investigated metabolites warrant further experimental validation.

This study introduces a new series of organic compounds (PPH1–PPH8) derived from a pyridine dipyrrolide (PDP) core, aimed at enhancing the efficacy of organic solar cells. Their light absorption and charge transport capabilities were improved by altering the terminal groups of a reference molecule (PPHR) with strong electron-withdrawing units. The density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations were employed at the M06/6-311G(d, p) level to examine the electronic and photovoltaic features of the designed chromophores. The findings indicated a notable redshift in the absorption spectra, broadening the absorption range from 562.874 to 617.913 nm accompanied by a substantial decrease in the energy gap from 2.677 to 2.468 eV in PPH1–PPH8. These results indicated enhanced solar light absorption due to end-capped modification. Moreover, these compounds demonstrated lower exciton binding energies (0.460–0.509 eV), signifying effective charge separation and improved exciton dissociation. Calculations of open-circuit voltage (V_oc), utilizing the standard acceptor (PC₇₁BM), further validated their photovoltaic potential. Electron-hole analysis identified PPH5 as a highly promising candidate, demonstrating significant spatial separation of charge carriers. Therefore, this research study presents a novel class of PDP-based chromophores with tailored optoelectronic characteristics, providing significant insights for the advancement of next-generation organic photovoltaic materials.