No abstract

Human Norovirus belong to family Calciviridae, it was identified in the outbreak of gastroenteritis in Norwalk, due to its seasonal prevalence known as "winter vomiting disease".Treatment of Norovirus infection is still mysterious because there is no effective antiviral drugs or vaccine developed to protect against the infection, to eradicate the infection an effective vaccine should be developed. In this study capsid protein (A7YK10), small protein (A7YK11) and polyprotein (A7YK09) were utilized. These proteins were subjected to B and T cell epitopes prediction by using reliable immunoinformatics tools. The antigenic and non-allergenic epitopes were selected for subunit vaccine, which can activate cellular and humoral immune responses.Linkers joined these epitopes together. The vaccine structure was modelled and validated by using Errat, ProSA and rampage servers. The modelled vaccine was docked with TLR-7.Stability of the docked complex was evaluated by MD simulation. In order to apply the concept in a wet lab, the reverse translated vaccine sequence was cloned in pET28a (+). The vaccine developed in this study requires experimental validation to ensure its effectiveness against the disease.

The outbreak of the recent coronavirus (SARS-CoV-2), which causes a severe pneumonia infection, first identified in Wuhan, China, imposes significant risks to public health. Around the world, researchers are continuously trying to identify small molecule inhibitors or vaccine candidates by targeting different drug targets. The SARs-CoV-2 macrodomain-I, which helps in viral replication and hijacking the host immune system, is also a potential drug target. Hence, this study targeted viral macrodomain-I by using drug similarity, virtual screening, docking and re-docking approaches. A total of 64,043 compounds were screened, and potential hits were identified based on the docking score and interactions with the key residues. The top six hits were subjected to molecular dynamics simulation and Free energy calculations and repeated three times each. The per-residue energy decomposition analysis reported that these compounds significantly interact with Asp22,

Backgroound: Lepidium pinnatifidum is a multipurpose, beneficial plant and known well for its indigenous therapeutic standards. Current study is aimed to investigate antioxidant and anti-inflammatory potency of Lepidium pinnatifidum. L. pinnatifidum dried powder was extracted with crude methanol (LPM) and then fractionated with various solvents to get respective fractions, termed as, n-hexane (LPH), chloroform (LPC), ethyl acetate (LPE), butanol (LPB) and the aqueous fraction (LPA). Fractions were evaluated for total flavonoid and phenolic content. Antioxidant profile was quantified via an array of antioxidant assays. Anti inflammatory activity was evaluated in vitro, and further assessed by in vivo study in Sprague Dawley rat. Result: Total phenolics (TPC) range from 48.15 ± 1.03-241.23 ± 1.07 mg GAE/g while total flavonoids (TFC) quantified were 16.32 ± 1.14-136.32 ± 1.14 mg RE/g. The in vitro antioxidant assays exhibited remarkable radicals scavenging action in different assays. Substantial positive correlation was instituted between TPC, TFC and various antioxidant assays. Inhibition of the heat induced protein denaturation reflected anti inflammatory potency, further supported by in vivo carrageenan induced paw edema. Conclusion: The obtained results lead to suggesting the therapeutic perspective of L. pinnatifidum in oxidative stress and inflammation associated ailments. The bio active ingredients behind its potential protectivity needs to be further confirmed.

Epstein-Barr Virus (EBV) is considered the most important human pathogen due to its role in infections and cellular malignancies. It has been reported that this Oncolytic virus infects 90% world’s population. EBNA1 is required for DNA binding and survival of the virus and is considered an essential drug target. The biochemical and structural properties of this protein are known, but it is still unclear which residues impart a critical role in the recognition of dsDNA. Intending to disclose only the essential residues in recognition of dsDNA, this study used a computational pipeline to generate an alanine mutant of each interacting residue and determine the impact on the binding. Our analysis revealed that R469A, K514A, Y518A, R521A and R522A are the key hotspots for the recognition of dsDNA by the EBNA1. The dynamics properties, i.e. stability, flexibility, structural compactness, hydrogen bonding frequency, binding affinity, are altered by disrupting the protein-DNA contacts, thereby decreases the binding affinity. In particular, the two arginine substitution, R521A and R522A, significantly affected the total binding energy. Thus, we hypothesize that these residues impart a critical role in the dsDNA recognition and pathogenesis. This study would help to design structure-based drugs against the EBV infections.