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NAD(P)H:quinone acceptor oxidoreductase-1 (NQO1) is a ubiquitous flavin adenine dinucleotide-dependent flavoprotein that promotes obligatory two-electron reductions of quinones, quinonimines, nitroaromatics, and azo dyes. NQO1 is a multifunctional antioxidant enzyme whose expression and deletion are linked to reduced and increased oxidative stress susceptibilities. NQO1 acts as both a tumor suppressor and tumor promoter; thus, the inhibition of NQO1 results in less tumor burden. In addition, the high expression of NQO1 is associated with a shorter survival time of cancer patients. Inhibiting NQO1 also enables certain anticancer agents to evade the detoxification process. In this study, a series of phytobioactives were screened based on their chemical classes such as coumarins, flavonoids, and triterpenoids for their action on NQO1. The in silico evaluations were conducted using PyRx virtual screening tools, where the flavone compound, Orientin showed a better binding affinity score of −8.18 when compared with standard inhibitor Dicumarol with favorable ADME properties. An MD simulation study found that the Orientin binding to NQO1 away from the substrate-binding site induces a potential conformational change in the substrate-binding site, thereby inhibiting substrate accessibility towards the FAD-binding domain. Furthermore, with this computational approach we are offering a scope for validation of the new therapeutic components for their in vitro and in vivo efficacy against NQO1.

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Bacterial infections are one of the leading causes of morbidity, mortality, and healthcare complications in patients. Leptospirosis is found to be the most prevalent, re-emergent, and neglected tropical zoonotic disease worldwide. The adaptation to various environmental conditions has made Leptospira acquire a large genome (~4.6 Mb) and a complex outer membrane, making it unique among bacteria that mimic the symptoms of jaundice and hemorrhage. Sph2 is another important virulence factor that enhances hemolytic sphingomyelinase—capable of moving inside mitochondria—which increases the ROS level and decreases the mitochondrial membrane potential, thereby leading to cell apoptosis. In the present study, 25 suspected bovine serum samples were subjected to the Microscopic Agglutination Test (MAT) across the Mysuru region. Different samples, such as urine, serum, and aborted materials from the confirmed MAT-positive animals, were used for isolation and genomic detection by conventional PCR targeting virulence gene, Lipl32, using specific primers. Further, in vitro and in silico studies were performed on isolated cultures to assess the anti-leptospiral, anti-hemolytic, and sphingomyelinase enzyme inhibition using novel pseudopeptides. The microdilution technique (MDT) and dark field microscope (DFM) assays revealed that at a concentration of 62.5 μg/mL, the pseudopeptide inhibited 100% of the growth of Leptospira spp., suggesting its efficiency in the treatment of leptospirosis. The flow cytometry analyses show the potency of the pseudopeptide against sphingomyelinase enzymes using human umbilical vein endothelial cells (HUVECs). Thus, the present study demonstrated the efficacy of the pseudopeptide in the inhibition of the growth of Leptospira, and therefore, this can be used as an alternative drug for the treatment of leptospirosis.