Design of novel pyrimidine based remdesivir analogues with dual target specificity for SARS CoV-2: A computational approach.

As the world undergone unpreceded time of tragedy with the corona virus, many researchers have raised to showcase their scientific contributions in terms of novel configured anti-viral drugs until now. Herein, we designed pyrimidine based nucleotides and assessed for the binding capability with SARS-CoV-2 viral replication targets of nsp12 RNA-dependent RNA polymerase and Mpro main protease. Molecular docking studies showed all the designed compounds to possess good binding affinity, with a few compounds which outperforms the control drug remdesivir GS-5743 and its active form GS-441524. Further molecular dynamics simulation studies confirmed their stability and preservation of the non-covalent interactions. Based on the present findings Ligand2-BzV_0Tyr, ligand3-BzV_0Ura, and ligand5-EeV_0Tyr showed good binding affinity with Mpro, whereas, ligand1-BzV_0Cys and Ligand2-BzV_0Tyr showed good binding affinity with RdRp, thus could act as potential lead compounds against SARS-CoV-2, which needs further validation studies. In particular, Ligand2-BzV_0Tyr could be more beneficial candidate with the dual target specificity for Mpro and RdRp.

Purification of PaTx-II from the Venom of the Australian King Brown Snake and Characterization of Its Antimicrobial and Wound Healing Activities.

Infections caused by multi-drug-resistant (MDR) bacteria are a global threat to human health. As venoms are the source of biochemically diverse bioactive proteins and peptides, we investigated the antimicrobial activity and murine skin infection model-based wound healing efficacy of a 13 kDa protein. The active component PaTx-II was isolated from the venom of Pseudechis australis (Australian King Brown or Mulga Snake). PaTx-II inhibited the growth of Gram-positive bacteria in vitro, with moderate potency (MICs of 25 µM) observed against S. aureus, E. aerogenes, and P. vulgaris. The antibiotic activity of PaTx-II was associated with the disruption of membrane integrity, pore formation, and lysis of bacterial cells, as evidenced by scanning and transmission microscopy. However, these effects were not observed with mammalian cells, and PaTx-II exhibited minimal cytotoxicity (CC50 > 1000 µM) toward skin/lung cells. Antimicrobial efficacy was then determined using a murine model of S. aureus skin infection. Topical application of PaTx-II (0.5 mg/kg) cleared S. aureus with concomitant increased vascularization and re-epithelialization, promoting wound healing. As small proteins and peptides can possess immunomodulatory effects to enhance microbial clearance, cytokines and collagen from the wound tissue samples were analyzed by immunoblots and immunoassays. The amounts of type I collagen in PaTx-II-treated sites were elevated compared to the vehicle controls, suggesting a potential role for collagen in facilitating the maturation of the dermal matrix during wound healing. Levels of the proinflammatory cytokines interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2) and interleukin-10 (IL-10), factors known to promote neovascularization, were substantially reduced by PaTx-II treatment. Further studies that characterize the contributions towards efficacy imparted by in vitro antimicrobial and immunomodulatory activity with PaTx-II are warranted.

Polyaza functionalized graphene oxide nanomaterial based sensor for Escherichia coli detection in water matrices.

Water quality is widely discussed owing to its significance in public health due to the inability to access clean water. Waterborne diseases account for the presence of pathogens like Escherichia coli (E. coli) in drinking water in the environmental community. Owing to the rapid increase of such bacterial microorganisms, a cost-effective sensor setup has been developed. Herein, we demonstrate the amine-functionalized graphene oxide (fGO) based 2D nanomaterial used to graft E. coli on its surface. The comparative analysis of the deposition of nanosheets on the glass substrate and PDMS was executed. The impedance variations of GO-based nanosensor at various concentrations of E. coli were performed and their potential difference was recorded. It was observed that the impedance changes inversely with the bacterial concentrations and was fed to the Arduino microcontroller. The experimental setup was standardized for the range of 0.01 Hz to 100 kHz. The obtained analog data was programmed with a microcontroller and the bacterial concentration in colony-forming units was displayed. The real-time analysis showsthe low-level detection of E. coli in aquatic environments. Experiments were conducted using the developed nanosensor to test the efficiency in complex water matrices and whose behavior changes with various physical, chemical, and environmental factors.

Copper(II)-Bis-Cyclen Intercalated Graphene Oxide as an Efficient Two-Dimensional Nanocomposite Material for Copper-Catalyzed Azide-Alkyne Cycloaddition Reaction.

We report stable and heterogeneous graphene oxide (GO)-intercalated copper as an efficient catalyst for the organic transformations in green solvents. The GO-intercalated copper(II) complex of bis(1,4,7,10-tetraazacyclododecane) [Cu(II)-bis-cyclen] was prepared by a facile synthetic approach with a high dilution technique. The as-prepared GO-Cu(II)-bis-cyclen nanocomposite was used as a click catalyst for the 1,3 dipolar Huisgen cycloaddition reaction of terminal alkyne and azide substrates. On directing a great deal of attention toward the feasibility of the rapid electron transfer rate of the catalyst in proliferating the yield of 1,2,3-triazole products, the click catalyst GO-Cu(II)-bis-cyclen nanocomposite was designed and synthesized via non-covalent functionalization. The presence of a higher coordination site in an efficient 2D nanocomposite promotes the stabilization of Cu(I) L-acetylide intermediate during the catalytic cycle initiated by the addition of reductants. From the XRD analysis, the enhancement in the d-interlayer spacing of 1.04 nm was observed due to the intercalation of the Cu(II)-bis-cyclen complex in between the GO basal planes. It was also characterized by XPS, FT-IR, RAMAN, UV, SEM, AFM, and TGA techniques. The recyclability of the heterogeneous catalyst [GO-Cu(II)-cyclen] with the solvent effect has also been studied. This class of GO-Cu(II)-bis-cyclen nanocomposite paves the way for bioconjugation of macromolecules through the click chemistry approach.

Tris-(2-aminoethyl)amine-Intercalated Graphene Oxide as an Efficient 2D Material for Cerium-Ion Fluorescent Sensor Applications.

In this work, we report the covalent functionalization of tris(2-aminoethyl)amine (tren) onto the graphene oxide surface by the ring opening of epoxide with primary amine moieties. The effect of intercalation creates the covalent coordinating moieties in between the basal planes of graphene oxide by increasing the interlayer spacing of 1.08 nm from 0.75 nm and thereby decreasing 2θ of 8.17 deg from 10.46 deg. Because of the intercalation of tren, the aminoalcohol moieties are formed in the GO planes and the intercalated material is characterized by the spectroscopic (IR, XPS, UV, and Fluorescence) and microscopic techniques. The DFT calculation shows the newly formed C-N bond length of 1.484 Šand enhanced energy gap due to functionalization. The intercalated material shows a good selective fluorescent chemosensor for the cerium ion in aqueous solution. The reversibility and its interference with other competing metal ions have been studied. The enhanced fluorescence upon the addition of cerium ions is due to the intramolecular charge transfer and photoinduced electron transfer processes in the sp2- and sp3-hybridized carbon networks.