BODIPY-fused uracil: synthesis, photophysical properties, and applications.

Fluorescent nucleobase and nucleic acid analogs are important tools in chemical and molecular biology as fluorescent labelling of nucleobases has applications in cellular imaging and anti-tumor activity. Boron-dipyrromethene (BODIPY) dyes exhibiting high brightness and good photostability are extensively used as fluorescent labelling agents and as type II photosensitizers for photodynamic therapy. Thus, the combination of nucleobases and BODIPY to obtain new compounds with both anti-tumor activity and fluorescent imaging functions is the focus of our research. We synthesized two new nucleobase analogs 1 and 2 by fusing the BODIPY core directly with uracil which resulted in favorable photophysical properties and high emission quantum efficiencies particularly in organic solvents. Further, we explored the newly synthesized derivatives, which possessed good singlet oxygen generation efficiencies and bio-compatibility, as potential PDT agents and our results show that they exhibit in vitro anti-tumor activities.

ARTISTRY-7: phase III trial of nemvaleukin alfa plus pembrolizumab vs chemotherapy for platinum-resistant ovarian cancer.

Standard single-agent nonplatinum chemotherapy provides only modest benefit in a small proportion of patients with platinum-resistant/-refractory ovarian cancer, with objective response rates of 6-20% and progression-free survival of ≈3-4 months. Nemvaleukin alfa (nemvaleukin, ALKS 4230) is a novel cytokine designed to capture and expand the therapeutic potential of high-dose interleukin-2 (IL-2) while mitigating its associated toxicity issues. Nemvaleukin preferentially activates cytotoxic CD8+ T cells and natural killer cells with minimal, non-dose-dependent effects on CD4+ regulatory T cells. The global, randomized, open-label, phase III ARTISTRY-7 trial will compare efficacy and safety of nemvaleukin plus pembrolizumab with chemotherapy in patients with platinum-resistant ovarian cancer. The primary end point is investigator-assessed progression-free survival. Clinical Trial Registration: GOG-3063; ENGOT-OV68; NCT05092360 (ClinicalTrials.gov).

In many patients with ovarian cancer who are treated with platinum-based chemotherapy, the tumor comes back after a few months and fails to respond to repeated treatment. This type of disease is called platinum-resistant ovarian cancer (PROC). Researchers are searching for new medicines to help more patients with PROC. One treatment approach that has shown promise in different cancers is called immunotherapy. These medicines work by helping the body's immune system attack cancer cells. One of the immunotherapies being studied is called nemvaleukin. It is designed to trigger specific immune responses that may result in the immune system attacking cancer cells while potentially avoiding other immune responses that can block the attack or cause certain unwanted side effects. Nemvaleukin is being studied in a variety of cancer types. In a worldwide clinical trial called ARTISTRY-7, researchers are investigating how nemvaleukin works in patients with PROC when given with another immunotherapy called pembrolizumab. Patients who participate in this trial will be randomly assigned to one of four treatment groups: the combination of nemvaleukin and pembrolizumab, nemvaleukin by itself, pembrolizumab by itself, or a type of chemotherapy selected by the treating physician. The main purpose of ARTISTRY-7 is to understand whether the combination of nemvaleukin and pembrolizumab helps patients with PROC live longer without their cancer getting worse. At the time of this writing, ARTISTRY-7 is open for new patients to join.

Reduction in postoperative sore throat by preoperative nebulization with dexmedetomidine, ketamine or saline: A prospective, randomized-controlled trial.

Background and Aims: Postoperative sore throat (POST) is a minor but distressing complication following general anesthesia. The current literature on the effect of preoperative nebulization with dexmedetomidine, or ketamine on POST is, however, sparse. So, we compared the effect of preoperative nebulization with these drugs on POST. Material and Methods: One hundred and thirty-two American Society of Anaesthesiology (ASA) grade I-II patients undergoing elective laparoscopic surgeries under general anesthesia were randomized into three equal groups: D, K, or C to receive dexmedetomidine, ketamine, or saline as preoperative nebulization, respectively. The primary objective was to compare the incidence and severity of POST, as inferred from the patient interviews at 2, 6, 12, 24-h postoperatively. Results: Group D had a significantly lower incidence (29.5%) and severity (12: mild; 1: moderate) of POST compared to group K (54.5% [21: mild; 3: moderate]) and group C (56.8% [19: mild; 6: moderate]), at 2-h postoperatively. The same trend was observed at 6-h postoperatively (group D: 22.7% [9: mild; 1: moderate]); group K: (40.9% [17: mild; 1: moderate]); group C (50% [17: mild; 5: moderate]). The mean arterial pressure was significantly lower in group D at 15 min intraoperatively (84.09 mmHg, P = 0.018) and immediate postoperatively (97.60 mmHg, P = 0.034). The postoperative sedation, nausea, and vomiting was not statistically significant. Conclusion: Preoperative nebulization with dexmedetomidine is effective in the reduction of the incidence and severity of early POST.

A pneumococcal pneumonia and influenza vaccination quality improvement program for women receiving chemotherapy for gynecologic cancers at a major tertiary cancer Centre.

OBJECTIVE: International guidelines recommend pneumococcal pneumonia and influenza vaccination for all patients with solid organ malignancies prior to initiating chemotherapy. Baseline vaccination rates (March 2019) for pneumococcal pneumonia and influenza at our tertiary cancer centre were 8% and 40%, respectively. The aim of this study was to increase the number of gynecologic chemotherapy patients receiving pneumococcal and influenza vaccinations to 80% by March 2020. METHODS: We performed an interrupted time series study using structured quality improvement methodology. Three interventions were introduced to address vaccination barriers: an in-house vaccination program, a staff education campaign, and a patient care bundle (pre-printed prescription, information brochure, vaccine record booklet). Process and outcome data were collected by patient survey and pharmacy audit and analyzed on statistical process control charts. RESULTS: We identified 195 eligible patients. Pneumococcal and influenza vaccination rates rose significantly from 5% to a monthly mean of 61% and from 36% to a monthly mean of 67%, respectively. The 80% target was reached for both vaccines during one or more months of study. The in-house vaccination and staff education programs were major contributors to the improvement, whereas the information brochure and record booklet were minor contributors. CONCLUSIONS: Three interventions to promote pneumococcal and influenza vaccination among chemotherapy patients resulted in significantly improved vaccination rates. Lessons learned about promoting vaccine uptake may be generalizable to different populations and vaccine types. In response to the global COVID-19 pandemic, initiatives to expand the program to all chemotherapy patients at our centre are underway.

SIFTS: updated Structure Integration with Function, Taxonomy and Sequences resource allows 40-fold increase in coverage of structure-based annotations for proteins.

The Structure Integration with Function, Taxonomy and Sequences resource (SIFTS; http://pdbe.org/sifts/) was established in 2002 and continues to operate as a collaboration between the Protein Data Bank in Europe (PDBe; http://pdbe.org) and the UniProt Knowledgebase (UniProtKB; http://uniprot.org). The resource is instrumental in the transfer of annotations between protein structure and protein sequence resources through provision of up-to-date residue-level mappings between entries from the PDB and from UniProtKB. SIFTS also incorporates residue-level annotations from other biological resources, currently comprising the NCBI taxonomy database, IntEnz, GO, Pfam, InterPro, SCOP, CATH, PubMed, Ensembl, Homologene and automatic Pfam domain assignments based on HMM profiles. The recently released implementation of SIFTS includes support for multiple cross-references for proteins in the PDB, allowing mappings to UniProtKB isoforms and UniRef90 cluster members. This development makes structure data in the PDB readily available to over 1.8 million UniProtKB accessions.

Adjuvant Trastuzumab Therapy: Can We Balance Efficacy and Safety?

Trastuzumab is an effective treatment for HER2-positive breast cancer. Current guidelines recommend withholding trastuzumab in patients experiencing a significant asymptomatic decline in left ventricular function. In this commentary, we discuss the survival benefits afforded by trastuzumab juxtaposed against the risk of trastuzumab-mediated cardiotoxicity. It is not known whether the net benefit of continuing trastuzumab in the setting of mild cardiotoxicity outweighs the associated risks. We describe a potential approach undertaken by our group, and others, and call for a randomized trial.

Host-induced silencing of Mi-msp-1 confers resistance to root-knot nematode Meloidogyne incognita in eggplant.

RNA interference (RNAi)-based host-induced gene silencing (HIGS) is emerging as a novel, efficient and target-specific tool to combat phytonematode infection in crop plants. Mi-msp-1, an effector gene expressed in the subventral pharyngeal gland cells of Meloidogyne incognita plays an important role in the parasitic process. Mi-msp-1 effector is conserved in few of the species of root-knot nematodes (RKNs) and does not share considerable homology with the other phytonematodes, thereby making it a suitable target for HIGS with minimal off-target effects. Six putative eggplant transformants harbouring a single copy RNAi transgene of Mi-msp-1 was generated. Stable expression of the transgene was detected in T1, T2 and T3 transgenic lines for which a detrimental effect on RKN penetration, development and reproduction was documented upon challenge infection with nematode juveniles. The post-parasitic nematode stages extracted from the transgenic plants showed long-term RNAi effect in terms of targeted downregulation of Mi-msp-1. These findings suggest that HIGS of Mi-msp-1 enhances nematode resistance in eggplant and protect the plant against RKN parasitism at very early stage.

Integrating population variation and protein structural analysis to improve clinical interpretation of missense variation: application to the WD40 domain.

We present a generic, multidisciplinary approach for improving our understanding of novel missense variants in recently discovered disease genes exhibiting genetic heterogeneity, by combining clinical and population genetics with protein structural analysis. Using six new de novo missense diagnoses in TBL1XR1 from the Deciphering Developmental Disorders study, together with population variation data, we show that the ß-propeller structure of the ubiquitous WD40 domain provides a convincing way to discriminate between pathogenic and benign variation. Children with likely pathogenic mutations in this gene have severely delayed language development, often accompanied by intellectual disability, autism, dysmorphology and gastrointestinal problems. Amino acids affected by likely pathogenic missense mutations are either crucial for the stability of the fold, forming part of a highly conserved symmetrically repeating hydrogen-bonded tetrad, or located at the top face of the ß-propeller, where 'hotspot' residues affect the binding of ß-catenin to the TBLR1 protein. In contrast, those altered by population variation are significantly less likely to be spatially clustered towards the top face or to be at buried or highly conserved residues. This result is useful not only for interpreting benign and pathogenic missense variants in this gene, but also in other WD40 domains, many of which are associated with disease.

Comparisons of Allergenic and Metazoan Parasite Proteins: Allergy the Price of Immunity.

Allergic reactions can be considered as maladaptive IgE immune responses towards environmental antigens. Intriguingly, these mechanisms are observed to be very similar to those implicated in the acquisition of an important degree of immunity against metazoan parasites (helminths and arthropods) in mammalian hosts. Based on the hypothesis that IgE-mediated immune responses evolved in mammals to provide extra protection against metazoan parasites rather than to cause allergy, we predict that the environmental allergens will share key properties with the metazoan parasite antigens that are specifically targeted by IgE in infected human populations. We seek to test this prediction by examining if significant similarity exists between molecular features of allergens and helminth proteins that induce an IgE response in the human host. By employing various computational approaches, 2712 unique protein molecules that are known IgE antigens were searched against a dataset of proteins from helminths and parasitic arthropods, resulting in a comprehensive list of 2445 parasite proteins that show significant similarity through sequence and structure with allergenic proteins. Nearly half of these parasite proteins from 31 species fall within the 10 most abundant allergenic protein domain families (EF-hand, Tropomyosin, CAP, Profilin, Lipocalin, Trypsin-like serine protease, Cupin, BetV1, Expansin and Prolamin). We identified epitopic-like regions in 206 parasite proteins and present the first example of a plant protein (BetV1) that is the commonest allergen in pollen in a worm, and confirming it as the target of IgE in schistosomiasis infected humans. The identification of significant similarity, inclusive of the epitopic regions, between allergens and helminth proteins against which IgE is an observed marker of protective immunity explains the 'off-target' effects of the IgE-mediated immune system in allergy. All these findings can impact the discovery and design of molecules used in immunotherapy of allergic conditions.

The Escherichia coli phosphotyrosine proteome relates to core pathways and virulence.

While phosphotyrosine modification is an established regulatory mechanism in eukaryotes, it is less well characterized in bacteria due to low prevalence. To gain insight into the extent and biological importance of tyrosine phosphorylation in Escherichia coli, we used immunoaffinity-based phosphotyrosine peptide enrichment combined with high resolution mass spectrometry analysis to comprehensively identify tyrosine phosphorylated proteins and accurately map phosphotyrosine sites. We identified a total of 512 unique phosphotyrosine sites on 342 proteins in E. coli K12 and the human pathogen enterohemorrhagic E. coli (EHEC) O157:H7, representing the largest phosphotyrosine proteome reported to date in bacteria. This large number of tyrosine phosphorylation sites allowed us to define five phosphotyrosine site motifs. Tyrosine phosphorylated proteins belong to various functional classes such as metabolism, gene expression and virulence. We demonstrate for the first time that proteins of a type III secretion system (T3SS), required for the attaching and effacing (A/E) lesion phenotype characteristic for intestinal colonization by certain EHEC strains, are tyrosine phosphorylated by bacterial kinases. Yet, A/E lesion and metabolic phenotypes were unaffected by the mutation of the two currently known tyrosine kinases, Etk and Wzc. Substantial residual tyrosine phosphorylation present in an etk wzc double mutant strongly indicated the presence of hitherto unknown tyrosine kinases in E. coli. We assess the functional importance of tyrosine phosphorylation and demonstrate that the phosphorylated tyrosine residue of the regulator SspA positively affects expression and secretion of T3SS proteins and formation of A/E lesions. Altogether, our study reveals that tyrosine phosphorylation in bacteria is more prevalent than previously recognized, and suggests the involvement of phosphotyrosine-mediated signaling in a broad range of cellular functions and virulence.

Mononuclear iron(iii) complexes of tridentate ligands with efficient nuclease activity and studies of their cytotoxicity.

Mononuclear mono- and bis-chelated iron(iii) complexes [Fe(Phimp)(H2O)(OMe)Cl], 1, [Fe(Phimp)Cl2], 2, [Fe(Me-Phimp)Cl2], 3, [Fe(N-Phimp)Cl2], 4, [Fe(Phimp)2](ClO4), 5, [Fe(Me-Phimp)2](NO3)·H2O, 6·H2O, and [Fe(N-Phimp)2](ClO4), 7, derived from tridentate ligands, have been synthesised and characterized. The X-ray crystal structures of the complexes 2, 4, 5 and 6·H2O were determined. The high-spin iron(iii) complexes were redox active and exhibited the Fe(iii)/Fe(ii) couple. The DNA binding affinity of these complexes was assessed using absorption, fluorescent intercalator displacement assays and circular dichroism spectral studies. Gel electrophoresis studies with DNA and complexes 1, 2, 3 and 6 showed efficient nuclease activity via a hydroxyl radical generated through a Fenton-type reaction mechanism. In situ reactive oxygen species generation has been further supported via DPPH (2,2-diphenyl-1-picrylhydrazine) radical quenching studies as well as theoretical studies. The cytotoxicities of the complexes were determined using the MCF7 cell line; the cytotoxicities (IC50 values) obtained for 1, 2, 3 and 5 were 0.67 ± 0.31, 0.46 ± 0.07, 0.87 ± 0.25 and 1.53 ± 0.41 µM, respectively, and complexes 1-6 were found to be non-toxic to normal HEK cell lines. An acridine orange staining assay for the complexes (1-6) supported cell death, probably via an apoptotic mechanism.

Formulation of Solid Lipid Nanoparticles Loaded with Rosiglitazone and Probiotic: Optimization and In-vitro Characterization.

INTRODUCTION: In the present study, solid lipid nanoparticles loaded with Rosiglitazone and probiotics were prepared via solvent emulsification diffusion. As a lipid and surfactant, Gleceryl monostearate and Pluronic -68 were used in the formulation process. METHOD: During characterization, it was determined that ingredient quantity variations significantly impacted Rosiglitazone loading capacity, particle size, polydispersity index, etc. In an optimized formulation of RSG-PB loaded SLNs, spherical particles with a mean particle size of 147.66±1.52 nm, PDI of 0.42±0.02, and loading capacity of 45.36±0.20 were identified. RESULT: Moreover, the developed SLNs had the potential to discharge the drug for up to 24 hours, as predicted by Higuchi's pharmacokinetic model. The SLNs were stable at 25°C/60%RH for up to 60 days. There was little to no change in particle size, PDI, or loading capacity. In addition, the number of probiotic bacteria was determined using the standard plate count procedure. Further, the antioxidant effect of the prepared formulation is evaluated using the DPPH assay method. CONCLUSION: This study concludes that the method used to fabricate RSG-probiotic-loaded SLNs is straightforward and yields favorable results regarding various parameters, including sustained release property, particle size, PDI, and percent drug loading stability. Furthermore, DPPH radical scavenging activity shows the high antioxidant potential of RSG-PB SLNs when compared to RSG and probiotics alone.

Multifunctional BODIPY embedded non-woven fabric for CO release and singlet oxygen generation.

Materials that can simultaneously release CO and generate singlet oxygen upon visible light irradiation under ambient conditions are highly desirable for therapeutic applications. Furthermore, materials that can sequester the undesirable side products into the matrix without affecting the release of CO and singlet oxygen generation would allow them to be used for practical applications. Focussing on these aspects, we prepared two dipicolylamine appended BODIPY­manganese(I) tricarbonyl complexes wherein the metal core was systematically tethered at 5- and 8- positions of the BODIPY core. The complexes were embedded into a polymer matrix via electrospinning and the resulting non-woven fabrics showed CO release as well as singlet oxygen generation upon irradiation. While the hybrid materials were non-toxic in dark, they were strongly photocytotoxic to c6 cancer cells when exposed to light. Rapid CO release alongside significant singlet oxygen generation, indefinite dark stability, good biocompatibility and negligible dark toxicity makes these fabrics a potent candidate for phototherapeutic applications.

Structural and molecular basis of interaction of HCV non-structural protein 5A with human casein kinase 1α and PKR.

BACKGROUND: Interaction of non-structural protein 5A (NS5A) of Hepatitis C virus (HCV) with human kinases namely, casein kinase 1α (ck1α) and protein kinase R (PKR) have different functional implications such as regulation of viral replication and evasion of interferon induced immune response respectively. Understanding the structural and molecular basis of interactions of the viral protein with two different human kinases can be useful in developing strategies for treatment against HCV. RESULTS: Serine 232 of NS5A is known to be phosphorylated by human ck1α. A structural model of NS5A peptide containing phosphoacceptor residue Serine 232 bound to ck1α has been generated using the known 3-D structures of kinase-peptide complexes. The substrate interacting residues in ck1α has been identified from the model and these are found to be conserved well in the ck1 family. ck1α - substrate peptide complex has also been used to understand the structural basis of association between ck1α and its other viral stress induced substrate, tumour suppressor p53 transactivation domain which has a crystal structure available.Interaction of NS5A with another human kinase PKR is primarily genotype specific. NS5A from genotype 1b has been shown to interact and inhibit PKR whereas NS5A from genotype 2a/3a are unable to bind and inhibit PKR efficiently. This is one of the main reasons for the varied response to interferon therapy in HCV patients across different genotypes. Using PKR crystal structure, sequence alignment and evolutionary trace analysis some of the critical residues responsible for the interaction of NS5A 1b with PKR have been identified. CONCLUSIONS: The substrate interacting residues in ck1α have been identified using the structural model of kinase - substrate peptide. The PKR interacting NS5A 1b residues have also been predicted using PKR crystal structure, NS5A sequence analysis along with known experimental results. Functional significance and nature of interaction of interferon sensitivity determining region and variable region 3 of NS5A in different genotypes with PKR which was experimentally shown are also supported by the findings of evolutionary trace analysis. Designing inhibitors to prevent this interaction could enable the HCV genotype 1 infected patients respond well to interferon therapy.

Aggregation-Induced Emission, Mechanofluorochromism, and Selective Fluoride Detection by a Tripodal Salicylaldimine.

Fluoride ions are indispensable in biology and environmental science and hence the selective and sensitive detection of fluoride is important. This work reports the design and synthesis of a tripodal Schiff's base 1 through a simple condensation reaction between a commercially available aldehyde and an amine. Single crystal X-ray crystallography revealed that compound 1 is a planar entity with the three salicylidene derivatives on the three arms of the central phenyl moiety linked by imine groups. Compound 1 forms a molecular dimer that resembles a six-petal flower and is stabilized through multiple intermolecular interactions such as C-H.π and π.π interactions. Compound 1 exhibited moderately good emission in the solid state with aggregation induced emission and reversible mechanofluorochromic properties. Moreover, 1 was observed to selectively detect fluoride among various anions with a limit of detection of ∼9 ppm. Compound 1 was also capable of detecting fluoride under a variety of conditions such as in thin films and under cellular conditions.

An assessment of various potentially toxic elements and associated health risks in agricultural soil along the middle Gangetic basin, India.

The present study analysed the levels of potentially toxic elements along with physico-chemical properties of agricultural soil samples (n = 59) collected from fields situated along the path of river Ganga in the middle Gangetic floodplain in two districts, Ballia and Ghazipur. Arsenic (As), chromium (Cr), copper (Cu), nickel (Ni), zinc (Zn), lead (Pb), iron (Fe) and manganese (Mn) levels were analysed by Wavelength Dispersive-X-Ray Fluorescence Spectroscopy (WD-XRF) and the associated health risks along with diverse indices were calculated. The mean concentrations of As, Cu, Cr, Pb, Zn and Ni were found to be 15, 42, 85, 18, 87 and 47 mg kg-1, respectively in Ballia and 13, 31, 73, 22, 77 and 34 mg kg-1, respectively in Ghazipur. Physico-chemical properties like pH, ORP and organic matter were found to be 7.91, 209 and 1.20, respectively in Ballia and 8.51, 155 and 1.25, respectively in Ghazipur. The calculated health quotient (HQ) for all the elements was observed to be within the threshold value of one, however with few exemptions. Therefore, the present study showcases the contamination of potentially toxic elements in agricultural fields and possible health hazards for people.

Identification and characterization of a novel deoxyhypusine synthase in Leishmania donovani.

Deoxyhypusine synthase, an NAD(+)-dependent enzyme, catalyzes the first step in the post-translational synthesis of an unusual amino acid, hypusine (N(epsilon)-(4-amino-2-hydroxybutyl)lysine), in the eukaryotic initiation factor 5A precursor protein. Two putative deoxyhypusine synthase (DHS) sequences have been identified in the Leishmania donovani genome, which are present on chromosomes 20: DHSL20 (DHS-like gene from chromosome 20) and DHS34 (DHS from chromosome 34). Although both sequences exhibit an overall conservation of key residues, DHSL20 protein lacks a critical lysine residue, and the recombinant protein showed no DHS activity in vitro. However, DHS34 contains the critical lysine residue, and the recombinant DHS34 effectively catalyzed deoxyhypusine synthesis. Furthermore, in vivo labeling confirmed that hypusination of eukaryotic initiation factor 5A occurs in intact Leishmania parasites. Interestingly, the DHS34 is much longer, with 601 amino acids, compared with the human DHS enzyme (369 amino acids) and contains several unique insertions. To study the physiological role of DHS34 in Leishmania, gene deletion mutations were attempted via targeted gene replacement. However, chromosomal null mutants of DHS34 could only be obtained in the presence of a DHS34-containing episome. The present data provide evidence that DHS34 is essential for L. donovani and that structural differences in the human and leishmanial DHS enzyme may be exploited for designing selective inhibitors against the parasite.

Novel diphenoxo-bridged dinuclear zinc complexes: generation of phenoxyl-radical species and nuclease activity.

Tridentate ligand PhimpH having N(2)O donors binds to zinc(II) after deprotonation, affording novel diphenoxo-bridged dinuclear zinc complexes [Zn(2)(Phimp)(2)(ClO(4))(2)] (1) and [Zn(2)(Phimp)(2)(Cl)(2)] x CH(2)Cl(2) (2 x CH(2)Cl(2)). The molecular structure of 2 x CH(2)Cl(2) revealed some unique structural features. The phenoxyl-radical complexes were generated at room temperature, and these radical complexes exhibited nuclease activity with pBR322 DNA.

Unity and diversity among viral kinases.

Viral kinases are known to undergo autophosphorylation and also phosphorylate viral and host substrates. Viral kinases have been implicated in various diseases and are also known to acquire host kinases for mimicking cellular functions and exhibit virulence. Although substantial analyses have been reported in the literature on diversity of viral kinases, there is a gap in the understanding of sequence and structural similarity among kinases from different classes of viruses. In this study, we performed a comprehensive analysis of protein kinases encoded in viral genomes. Homology search methods have been used to identify kinases from 104,282 viral genomic datasets. Serine/threonine and tyrosine kinases are identified only in 390 viral genomes. Out of seven viral classes that are based on nature of genetic material, only viruses having double-stranded DNA and single-stranded RNA retroviruses are found to encode kinases. The 716 identified protein kinases are classified into 63 subfamilies based on their sequence similarity within each cluster, and sequence signatures have been identified for each subfamily. 11 clusters are well represented with at least 10 members in each of these clusters. Kinases from dsDNA viruses, Phycodnaviridae which infect green algae and Herpesvirales that infect vertebrates including human, form a major group. From our analysis, it has been observed that the protein kinases in viruses belonging to same taxonomic lineages form discrete clusters and the kinases encoded in alphaherpesvirus form host-specific clusters. A comprehensive sequence and structure-based analysis enabled us to identify the conserved residues or motifs in kinase catalytic domain regions across all viral kinases. Conserved sequence regions that are specific to a particular viral kinase cluster and the kinases that show close similarity to eukaryotic kinases were identified by using sequence and three-dimensional structural regions of eukaryotic kinases as reference. The regions specific to each viral kinase cluster can be used as signatures in the future in classifying uncharacterized viral kinases. We note that kinases from giant viruses Marseilleviridae have close similarity to viral oncogenes in the functional regions and in putative substrate binding regions indicating their possible role in cancer.