A5068052161- Monoclonal and Polyclonal Antibodies Research
- Transgenic Plants and Applications
- Glycosylation and Glycoproteins Research
- Biochemical and Structural Characterization
- Chemical Synthesis and Analysis
- Bacteriophages and microbial interactions
- Mosquito-borne diseases and control
- Cancer therapeutics and mechanisms
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- Microbial Natural Products and Biosynthesis
- Viral Infectious Diseases and Gene Expression in Insects
- SARS-CoV-2 and COVID-19 Research
- Advanced Biosensing Techniques and Applications
- Synthesis and Biological Activity
- Biochemical and Molecular Research
- Microbial Metabolism and Applications
- Virology and Viral Diseases
- Viral Infections and Outbreaks Research
- Cancer Mechanisms and Therapy
- Marine Sponges and Natural Products
- Pharmacological Effects of Natural Compounds
- Plant Virus Research Studies
- Toxin Mechanisms and Immunotoxins
- Synthesis and Characterization of Heterocyclic Compounds
Target (United States)
2015-2025
National Cancer Institute
2007-2025
Center for Cancer Research
2014-2025
Frederick National Laboratory for Cancer Research
2014-2023
Leidos (United States)
2014-2023
National Institutes of Health
2014-2019
Leidos Biomedical Research Inc. (United States)
2014-2017
Science Applications International Corporation (United States)
2006-2013
Identifying small molecules that selectively bind to structured RNA motifs remains an important challenge in developing potent and specific therapeutics. Most strategies find RNA-binding have identified highly charged compounds or aminoglycosides commonly modest selectivity. Here we demonstrate a strategy screen large unbiased library of druglike microarray format against target. This approach has enabled the identification novel chemotype targets HIV transactivation response (TAR) hairpin...
Abstract Nipah virus (NiV) is a highly pathogenic zoonotic paramyxovirus that causes fatal encephalitis and respiratory disease in humans. There currently no approved therapeutic for human use against NiV infection. Griffithsin (GRFT) high-mannose oligosaccharide binding lectin has shown vivo broad-spectrum activity viruses, including severe acute syndrome coronavirus, immunodeficiency 1, hepatitis C virus, Japanese virus. In this study, we evaluated the vitro antiviral activities of GRFT...
We investigated whether the T7 system of phage display could produce peptide libraries greater diversity than M13 due to differing processes lytic and filamentous morphogenesis. Using a bioinformatics-assisted computational approach, collections random sequences obtained from 12-mer library (X(12)) 7-mer disulfide-constrained (CX(7)C) were analyzed compared with populations New England BioLabs' Ph.D.-12 Ph.D.-C7C libraries. Based on this analysis, constructed have fewer amino acid biases,...
Monoclonal antibodies have been successfully utilized as cancer-targeting therapeutics and diagnostics, but the efficacies of these treatments are limited in part by size molecules non-specific uptake reticuloendothelial system. Peptides much smaller that can specifically target cancer cells such may alleviate complications with antibody therapy. Although many endogenous exogenous peptides developed into clinical therapeutics, only a subset consists peptides. Combinatorial biological...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped positive stranded RNA virus which has caused the recent deadly pandemic called COVID-19. The SARS-CoV-2 virion coated with a heavily glycosylated Spike glycoprotein responsible for attachment and entry into target cells. One, as yet unexploited strategy preventing infections, targeting of glycans on Spike. Lectins are carbohydrate-binding proteins produced by plants, algae, cyanobacteria. Some lectins can neutralize...
An anti-HIV screening of natural product extracts resulted in the discovery a new antiviral protein through bioassay-guided fractionation an aqueous extract ascidian Didemnum molle. The was sequenced combination tandem mass spectroscopy and N-terminal Edman degradation peptide fragments after series endoproteinase digestions. primary amino acid sequence disulfide bonding pattern 102-amino were closely related to cyanovirin-N (CV-N). This CV-N homolog named Dm-CVNH. Alphafold2 prediction...
The lectin griffithsin (GRFT) is a potent antiviral agent capable of prevention and treatment infections caused by number enveloped viruses currently under development as an anti-HIV microbicide. In addition to its broad activity, GRFT stable at high temperature pH range, displays little toxicity immunogenicity, amenable large-scale manufacturing. Native domain-swapped homodimer that binds viral envelope glycoproteins has displayed mid-picomolar activity in cell-based assays. Previously, we...
Abstract Background Amino acid sequence diversity is introduced into a phage-displayed peptide library by randomizing oligonucleotide DNA. We recently evaluated the of libraries displayed on T7 lytic phage and M13 filamentous showed that can display more diverse amino repertoire due to differing processes viral morphogenesis. Methods In this study, we compared 12-mer randomized using codon-corrected trinucleotide cassettes with an constructed degenerate codon randomization method. Results...
Abstract The crystal structures of the natural and recombinant antiviral lectin scytovirin (SVN) were solved by single‐wavelength anomalous scattering refined with data extending to 1.3 Å 1.0 resolution, respectively. A molecule SVN consists a single chain 95 amino acids long, an almost perfect sequence repeat that creates two very similar domains (RMS deviation 0.25 for 40 pairs Cα atoms). structure differs significantly from previously published NMR same protein, RMS deviations calculated...
This study describes the cell-free biomanufacturing of a broad-spectrum antiviral protein, griffithsin (GRFT) such that it can be produced in microgram quantities with consistent purity and potency less than 24 h. We demonstrate GRFT production using two independent systems, one plant microbial. Griffithsin quality were verified standard regulatory metrics. Efficacy was demonstrated vitro against SARS-CoV-2 HIV-1 nearly identical to expressed vivo. The proposed process is efficient readily...
Combinatorial peptide library technology is a valuable resource for drug discovery and development. Several drugs developed through phage-displayed are presently in clinical trials the authors envision that will assist development of many more. This review attempts to compile summarize recent literature on targeting peptides technology, with special emphasis novel capacity evaluated vivo.
Tyrosyl-DNA phosphodiesterase 1 (TDP1) is an enzyme crucial for cleavage of the covalent topoisomerase 1-DNA complex, intermediate in DNA repair. TDP1 plays a role reversing inhibition I by camptothecins, series potent and effective inhibitors used treatment colorectal, ovarian, small-cell lung cancers. It hypothesized that activity may enhance camptothecin sensitivity tumors. Here, we describe design, development, execution novel assay to identify present natural product extracts. The was...
Bioassay-guided separation of an extract from a Dictyosporium sp. isolate led to the identification six new compounds, 1–6, together with five known 7–11. The structures compounds were primarily established by extensive 1D and 2D NMR experiments. absolute configurations 3–6 determined comparison their experimental electronic circular dichroism (ECD) spectra DFT quantum mechanical calculated ECD spectra. Compounds 3–5 possess novel structural scaffolds, biochemical studies revealed that...
Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a molecular target for the sensitization of cancer cells to FDA-approved topoisomerase inhibitors topotecan and irinotecan. High-throughput screening natural product extract fraction libraries TDP1 activity resulted in discovery new class knotted cyclic peptides from marine sponge Axinella sp. Bioassay-guided fractionation source isolation active component which was determined be an unprecedented 42-residue cysteine-rich peptide named recifin A. The...
Chemical synthesis of the peptide recifin A reveals insights into its unique structure and interaction with cancer target TDP1.
Cyanovirin-N (CV-N) is an antiviral lectin with potent activity against enveloped viruses, including HIV. The mechanism of action involves high affinity binding to mannose-rich glycans that decorate the surface viruses. In case HIV, CV-N postulated require multivalent interactions envelope protein gp120, achieved through a pseudo-repeat sequence adopts two near-identical glycan-binding sites, and possibly 3D-domain-swapped dimeric form CV-N. Here, we present covalent dimer increases number...
A new 11 amino acid linear peptide named roseabol (1) and the known compound 13-oxo-trans-9,10-epoxy-11(E)-octadecenoic (2) were isolated from fungus Clonostachys rosea. Combined NMR MS analysis revealed that contained residues characteristic of peptaibol family peptides such as isovaline, α-aminoisobutyric acid, hydroxyproline, leucinol, an N-terminal isovaleric moiety. The sequence was established by a combination studies tandem fragmentation analyses, absolute configurations constituent...
MoMo30 is an antiviral protein isolated from aqueous extracts of Momordica balsamina L. (Senegalese bitter melon). Previously, we demonstrated MoMo30’s activity against HIV-1. Here, explore whether has the COVID-19 virus, SARS-CoV-2. MLV particles pseudotyped with SARS-CoV-2 Spike glycoprotein and a Luciferase reporter gene (SARS2-PsV) were developed three-way co-transfection HEK293-T17 cells. inhibition SARS2-PsV infection was measured using luciferase assay its cytotoxicity XTT assay....
An estimated 34 million people are living with the human immunodeficiency virus (HIV) worldwide. Increasing resistance to antiretrovirals (ARVs) challenges current therapies and it is critical identify novel non‐ARV anti‐HIV agents prevent infection. Here we report isolation of a class proteins, called Cnidarins, from soft coral Synthecium sp. (phylum Cnidaria). The proteins were purified by sequential ethanol ammonium sulphate precipitation followed hydrophobic interaction chromatography....
This study describes the cell-free biomanufacturing of a broad-spectrum antiviral protein, griffithsin (GRFT) such that it can be produced with consistent purity and potency in less than 24 hours. We demonstrate GRFT production using two independent systems, one plant microbial. Griffithsin quality were verified standard regulatory metrics. Efficacy was demonstrated vitro against SARS-CoV-2 HIV-1 nearly identical to expressed vivo . The proposed process is efficient readily scaled up...