Recent advances in the discovery of potent RNA-dependent RNA-polymerase (RdRp) inhibitors targeting viruses  Recent

advances in the discovery of potent RNA-dependent RNA-polymerase (RdRp) inhibitors targeting viruses  Recent advances in the discovery of potent RNA-dependent RNA-polymerase (RdRp) inhibitors targeting viruses  Recent advances in the discovery of potent RNA-dependent RNA-polymerase (RdRp) inhibitors targeting viruses

Raman Kumar, Vinesh Sharma, Sampa Das, Vikram Patial and Vidyashankar Srivatsan

Abstract

The present study was aimed at developing Arthrospira platensis (Spirulina) fortified traditional foods of the Indian subcontinent, namely sattu (multigrain beverage mix) and chikki (peanut bar) and evaluating their ability to promote recovery from protein and iron deficiency anaemia (IDA) using albino Wistar rats. Addition of Spirulina (at 4% w/w Spirulina inclusion levels) enriched the protein content by 20.33% in sattu and 15.65% in chikki while the iron content was enhanced by 45% in sattu and 29.6% in chikki. In addition, the total carotenoid and polyphenol content and antioxidant capacity of the food products improved after Spirulina incorporation. Supplementation of 100 g of Spirulina fortified food products meets more than 50% of recommended dietary allowances (RDA) of protein, dietary fiber, iron and zinc for the age group 3 to 10 years of children. Spirulina contributed between 11% and 22% of RDA for protein and iron, respectively; however it contributed very negligibly to RDA of dietary fibre with respect to the nutrient requirements for the target age group. Supplementation of Spirulina fortified foods individually promoted bodyweight gain in malnourished rats and restored haemoglobin, serum protein, albumin, serum iron, and hepcidin levels and reduced the iron binding capacity indicating recovery from IDA. Spirulina supplementation ameliorated malnutrition induced oxidative stress in the liver, spleen and kidneys by reducing the lipid peroxidation and enhancing superoxide dismutase and glutathione activities. Histopathological analysis revealed that supplementation of Spirulina fortified foods reversed pathological changes such as fatty changes in the liver cells, thinning of cardiac muscle fibers and degeneration of intestinal villi. Fe–protein deficiency significantly altered the gut microflora by reducing the abundance of beneficial microbes. However, supplementation of Spirulina fortified foods improved the levels of beneficial gut microbes such as Lactobacillus reuteri and Akkermansia muciniphila while reducing the abundance of Helicobacteraceae, Enterobacteria and Clostridia. In summary, supplementation of Spirulina fortified foods promoted recovery from protein and iron deficiency indicating the bioavailability of nutrients (iron and protein) from Spirulina at par with casein and ferrous ascorbate.

Journal: Food and Function

Neeraj Kumar and Vishal Acharya

Abstract

The human immunodeficiency virus (HIV) connects to the cluster of differentiation (CD4) and any of the entry co-receptors (CCR5 and CXCR4); followed by unloading the viral genome, reverse transcriptase, and integrase enzymes within the host cell. The co-receptors facilitate the entry of virus and vital enzymes, leading to replication and pre-maturation of viral particles within the host. The protease enzyme transforms the immature viral vesicles into the mature virion. The pivotal role of co-receptors and enzymes in homeostasis and growth makes the crucial target for anti-HIV drug discovery, and the availability of X-ray crystal structures is an asset. Here, we used the machine intelligence-driven framework (A-HIOT) to identify and optimize target-based potential hit molecules for five significant protein targets from the ZINC15 database (natural products dataset). Following validation with dynamic motion behavior analysis and molecular dynamics simulation, the optimized hits were evaluated using in silico ADMET filtration. Furthermore, three molecules were screened, optimized, and validated: ZINC00005328058 for CCR5 and protease, ZINC000254014855 for CXCR4 and integrase, and ZINC000000538471 for reverse transcriptase. In clinical trials, the ZINC000254014855 and ZINC000254014855 were passed in primary screens for vif-HIV-1, and we reported the specific receptor as well as interactions. As a result, the validated molecules may be investigated further in experimental studies targeting specific receptors in order to design and synergize an anti-HIV regimen.

Computers in Biology and Medicine (IF 6.698)

The upsurge of lytic polysaccharide monooxygenases in biomass deconstruction: characteristic functions and sustainable applications

Asheesh Kumar, Aishwarya Singh, Vijay Kumar Sharma, Akshita Goel, Arun Kumar

Abstract

Lytic polysaccharide monooxygenases (LPMOs) are one of the emerging classes of copper metalloenzymes that have received considerable attention due to their ability to boost the enzymatic conversion of intractable polysaccharides such as plant cell walls and chitin polymers. LPMOs catalyze the oxidative cleavage of β-1,4-glycosidic bonds using molecular O₂ or H₂O₂ in the presence of an external electron donor. LPMOs have been classified as an auxiliary active (AA) class of enzymes and, further based on substrate specificity, divided into eight families. Until now, multiple LPMOs from AA9 and AA10 families, mostly from microbial sources, have been investigated; the exact mechanism and structure–function are elusive to date, and recently discovered AA families of LPMOs are just scratched. This review highlights the origin and discovery of the enzyme, nomenclature, three-dimensional protein structure, substrate specificity, copper-dependent reaction mechanism, and different techniques used to determine the product formation through analytical and biochemical methods. Moreover, the diverse functions of proteins in various biological activities such as plant–pathogen/pest interactions, cell wall remodeling, antibiotic sensitivity of biofilms, and production of nanocellulose along with certain obstacles in deconstructing the complex polysaccharides have also been summarized, while highlighting the innovative and creative ways to overcome the limitations of LPMOs in hydrolyzing the biomass.

Journal: FEBS Journal (IF 5.6)

Vidhi Raturi, Surbhi Mali, Gaurav Zinta

Abstract