NMR-Based Metabolomics: A New Paradigm to Unravel Defense-Related Metabolites in Insect-Resistant Cotton Variety through Different Multivariate Data Analysis Approaches.

Cotton () is an economically important crop and is widely cultivated around the globe. However, the major problem of cotton is its high vulnerability to biotic and abiotic stresses. It has been around three decades since the cotton plant was genetically engineered with genes encoding insecticidal proteins (mainly Cry proteins) with an aim to protect it against insect attack.

Identification and Characterization of Natural and Semisynthetic Quinones as Aurora Kinase Inhibitors.

Aurora kinases (Aurora A, B, and C) are a family of serine/threonine kinases that play critical roles during mitotic initiation and progression. Aurora A and B kinases are ubiquitously expressed, and their overexpression and/or amplification in many cancers have been associated with poor prognosis. Several inhibitors that target Aurora kinases A, B, or both have been developed during the past decade with efficacy in different in vitro and in vivo models for a variety of cancers.

RIN4 homologs from important crop species differentially regulate the Arabidopsis NB-LRR immune receptor, RPS2.

RIN4 homologs from important crop species differ in their ability to prevent ectopic activity of the nucleotide binding-leucine rich repeat resistance protein, RPS2. Pathogens deploy virulence effectors to perturb host processes. Plants utilize intracellular resistance (R) proteins to recognize pathogen effectors either by direct interaction or indirectly via effector-mediated perturbations of host components.

Characterization of linear epitope specificity of antibodies potentially contributing to spontaneous clearance of hepatitis C virus.

Background: Around 30% of the HCV infected patients can spontaneously clear the virus. Cumulative evidence suggests the role of neutralizing antibodies in such spontaneous resolution. Understanding the epitope specificity of such antibodies will inform the rational vaccine design as such information is limited to date.

H-NMR-Based Metabolomics: An Integrated Approach for the Detection of the Adulteration in Chicken, Chevon, Beef and Donkey Meat.

Meat is a rich source of energy that provides high-value animal protein, fats, vitamins, minerals and trace amounts of carbohydrates. Globally, different types of meats are consumed to fulfill nutritional requirements. However, the increasing burden on the livestock industry has triggered the mixing of high-price meat species with low-quality/-price meat.

Structural insights of key enzymes into therapeutic intervention against SARS-CoV-2.

COVID-19 pandemic, caused by SARS-CoV-2, has drastically affected human health all over the world. After the emergence of the pandemic the major focus of efforts to attenuate the infection has been on repurposing the already approved drugs to treat COVID-19 adopting a fast-track strategy. However, to date a specific regimen to treat COVID-19 is not available.

Identification of potential inhibitors of three key enzymes of SARS-CoV2 using computational approach.

The recent outbreak of coronavirus disease-19 (COVID-19) continues to drastically affect healthcare throughout the world. To date, no approved treatment regimen or vaccine is available to effectively attenuate or prevent the infection. Therefore, collective and multidisciplinary efforts are needed to identify new therapeutics or to explore effectiveness of existing drugs and drug-like small molecules against SARS-CoV-2 for lead identification and repurposing prospects.

An Engineered Microvirin Variant with Identical Structural Domains Potently Inhibits Human Immunodeficiency Virus and Hepatitis C Virus Cellular Entry.

Microvirin (MVN) is one of the human immunodeficiency virus (HIV-1) entry inhibitor lectins, which consists of two structural domains sharing 35% sequence identity and contrary to many other antiviral lectins, it exists as a monomer. In this study, we engineered an MVN variant, LUMS1, consisting of two domains with 100% sequence identity, thereby reducing the chemical heterogeneity, which is a major factor in eliciting immunogenicity. We determined carbohydrate binding of LUMS1 through NMR chemical shift perturbation and tested its anti-HIV activity in single-round infectivity assay and its anti-hepatitis C virus (HCV) activity in three different assays including HCVcc, HCVpp, and replicon assays.

Estimation of hepatitis C prevalence in the Punjab province of Pakistan: A retrospective study on general population.

Background: Hepatitis C virus (HCV) infections are amongst the leading public health concerns in Pakistan with a high disease burden. Despite the availability of effective antiviral treatments in the country the disease burden in general population has not lowered. This could be attributed to the asymptomatic nature of this infection that results in lack of diagnosis until the late symptomatic stage.

Evolution of efficacious pangenotypic hepatitis C virus therapies.

Hepatitis C compromises the quality of life of more than 350 million individuals worldwide. Over the last decade, therapeutic regimens for treating hepatitis C virus (HCV) infections have undergone rapid advancements. Initially, structure-based drug design was used to develop molecules that inhibit viral enzymes.

Potential targets for therapeutic intervention and structure based vaccine design against Zika virus.

Continuously increasing number of reports of Zika virus (ZIKV) infections and associated severe clinical manifestations, including autoimmune abnormalities and neurological disorders such as neonatal microcephaly and Guillain-Barré syndrome have created alarming situation in various countries. To date, no specific antiviral therapy or vaccine is available against ZIKV. This review provides a comprehensive insight into the potential therapeutic targets and describes viral epitopes of broadly neutralizing antibodies (bNAbs) in vaccine design perspective.

CDK1 inhibition facilitates formation of syncytiotrophoblasts and expression of human Chorionic Gonadotropin.

Aims: The human placental syncytiotrophoblast (STB) cells play essential roles in embryo implantation and nutrient exchange between the mother and the fetus. STBs are polyploid which are formed by fusion of diploid cytotrophoblast (CTB) cells. Abnormality in STBs formation can result in pregnancy-related disorders.

A Neutralizing Antibody Recognizing Primarily N-Linked Glycan Targets the Silent Face of the HIV Envelope.

Virtually the entire surface of the HIV-1-envelope trimer is recognized by neutralizing antibodies, except for a highly glycosylated region at the center of the "silent face" on the gp120 subunit. From an HIV-1-infected donor, #74, we identified antibody VRC-PG05, which neutralized 27% of HIV-1 strains. The crystal structure of the antigen-binding fragment of VRC-PG05 in complex with gp120 revealed an epitope comprised primarily of N-linked glycans from N262, N295, and N448 at the silent face center.

Insights from NMR Spectroscopy into the Conformational Properties of Man-9 and Its Recognition by Two HIV Binding Proteins.

Man GlcNAc (Man-9) present at the surface of HIV makes up the binding sites of several HIV-neutralizing agents and the mammalian lectin DC-SIGN, which is involved in cellular immunity and trans-infections. We describe the conformational properties of Man-9 in its free state and when bound by the HIV entry-inhibitor protein microvirin (MVN), and define the minimum epitopes of both MVN and DC-SIGN by using NMR spectroscopy. To facilitate the implementation of 3D C-edited spectra to deconvolute spectral overlap and to determine the solution structure of Man-9, we developed a robust expression system for the production of C, N-labeled glycans in mammalian cells.

Phytochemistry of Daphne oleoides.

Genus Daphne belongs to the Thymelaeaceae family and consists of 70 species. Its various species exist in Europe, Philippine Islands, temperate and subtropical Asia, North Africa, Australia and Pacific. In Pakistan, Daphne is represented by three species.

Prostratin: An Overview.

Terpenoid class of molecules possesses a diverse therapeutic properties and potentials owing to their specific structural features. Prostratin and its derivatives are exemplified in this context to exhibit a variety of biological activities. In this review we discuss in detail the role of prostratin as potential therapeutic and underlying molecular mechanisms by which it accomplishes these activities.

Inhibition of hepatitis C virus by the cyanobacterial protein Microcystis viridis lectin: mechanistic differences between the high-mannose specific lectins MVL, CV-N, and GNA.

Plant or microbial lectins are known to exhibit potent antiviral activities against viruses with glycosylated surface proteins, yet the mechanism(s) by which these carbohydrate-binding proteins exert their antiviral activities is not fully understood. Hepatitis C virus (HCV) is known to possess glycosylated envelope proteins (gpE1E2) and to be potently inhibited by lectins. Here, we tested in detail the antiviral properties of the newly discovered Microcystis viridis lectin (MVL) along with cyanovirin-N (CV-N) and Galanthus nivalis agglutinin (GNA) against cell culture HCV, as well as their binding properties toward viral particles, target cells, and recombinant HCV glycoproteins.

Characterizing carbohydrate-protein interactions by nuclear magnetic resonance spectroscopy.

Interactions between proteins and soluble carbohydrates and/or surface displayed glycans are central to countless recognition, attachment and signaling events in biology. The physical chemical features associated with these binding events vary considerably, depending on the biological system of interest. For example, carbohydrate-protein interactions can be stoichiometric or multivalent, the protein receptors can be monomeric or oligomeric, and the specificity of recognition can be highly stringent or rather promiscuous.

Structural basis for diverse N-glycan recognition by HIV-1-neutralizing V1-V2-directed antibody PG16.

HIV-1 uses a diverse N-linked-glycan shield to evade recognition by antibody. Select human antibodies, such as the clonally related PG9 and PG16, recognize glycopeptide epitopes in the HIV-1 V1-V2 region and penetrate this shield, but their ability to accommodate diverse glycans is unclear. Here we report the structure of antibody PG16 bound to a scaffolded V1-V2, showing an epitope comprising both high mannose-type and complex-type N-linked glycans.

Characterization and carbohydrate specificity of pradimicin S.

The pradimicin family of antibiotics is attracting attention due to its anti-infective properties and as a model for understanding the requirements for carbohydrate recognition by small molecules. Members of the pradimicin family are unique among natural products in their ability to bind sugars in a Ca(2+)-dependent manner, but the oligomerization to insoluble aggregates that occurs upon Ca(2+) binding has prevented detailed characterization of their carbohydrate specificity and biologically relevant form. Here we take advantage of the water solubility of pradimicin S (PRM-S), a sulfated glucose-containing analogue of pradimicin A (PRM-A), to show by NMR spectroscopy and analytical ultracentrifugation that at biologically relevant concentrations, PRM-S binds Ca(2+) to form a tetrameric species that selectively binds and engulfs the trisaccharide Manα1-3(Manα1-6)Man over mannose or mannobiose.

Peptides from second extracellular loop of C-C chemokine receptor type 5 (CCR5) inhibit diverse strains of HIV-1.

To initiate HIV entry, the HIV envelope protein gp120 must engage its primary receptor CD4 and a coreceptor CCR5 or CXCR4. In the absence of a high resolution structure of a gp120-coreceptor complex, biochemical studies of CCR5 have revealed the importance of its N terminus and second extracellular loop (ECL2) in binding gp120 and mediating viral entry. Using a panel of synthetic CCR5 ECL2-derived peptides, we show that the C-terminal portion of ECL2 (2C, comprising amino acids Cys-178 to Lys-191) inhibit HIV-1 entry of both CCR5- and CXCR4-using isolates at low micromolar concentrations.

Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9.

Variable regions 1 and 2 (V1/V2) of human immunodeficiency virus-1 (HIV-1) gp120 envelope glycoprotein are critical for viral evasion of antibody neutralization, and are themselves protected by extraordinary sequence diversity and N-linked glycosylation. Human antibodies such as PG9 nonetheless engage V1/V2 and neutralize 80% of HIV-1 isolates. Here we report the structure of V1/V2 in complex with PG9.

Structural basis for norovirus inhibition and fucose mimicry by citrate.

Human noroviruses bind with their capsid-protruding domains to histo-blood-group antigens (HBGAs), an interaction thought to direct their entry into cells. Although human noroviruses are the major cause of gastroenteritis outbreaks, development of antivirals has been lacking, mainly because human noroviruses cannot be cultivated. Here we use X-ray crystallography and saturation transfer difference nuclear magnetic resonance (STD NMR) to analyze the interaction of citrate with genogroup II (GII) noroviruses.

Solution structure of the monovalent lectin microvirin in complex with Man(alpha)(1-2)Man provides a basis for anti-HIV activity with low toxicity.

Lectins that bind surface envelope glycoprotein gp120 of HIV with high avidity can potently inhibit viral entry. Yet properties such as multivalency that facilitate strong interactions can also cause nonspecific binding and toxicity. The cyanobacterial lectin microvirin (MVN) is unusual as it potently inhibits HIV-1 with negligible toxicity compared with cyanovirin-N (CVN), its well studied antiviral homolog.

Unprecedented glycosidase activity at a lectin carbohydrate-binding site exemplified by the cyanobacterial lectin MVL.

Carbohydrate binding proteins, or lectins, are engendered with the ability to bind specific carbohydrate structures, thereby mediating cell-cell and cell-pathogen interactions. Lectins are distinct from carbohydrate modifying enzymes and antibodies, respectively, as they do not carry out glycosidase or glycosyl transferase reactions, and they are of nonimmune origin. Cyanobacterial and algal lectins have become prominent in recent years due to their unique biophysical traits, such as exhibiting novel protein folds and unusually high carbohydrate affinity, and ability to potently inhibit HIV-1 entry through high affinity carbohydrate-mediated interactions with the HIV envelope glycoprotein gp120.