New strategies for antiviral research are urgently requested considering the growing number of emerging viruses as well as the viral variants resistant to existing antiviral molecules used for therapy. Phage-display is a powerful technology to select unique molecules with selective affinity for a specific target from libraries of huge diversity. This promising technology to isolate candidates or to improve their affinity for the target has been explored specifically for antiviral drug discovery. Phage display consists of presenting peptides/proteins at the bacteriophage surface by fusing their gene with that of a capsid protein of the phage. Upon library screening, the sequence of the selected peptide/protein is easily deduced from the DNA of the recombinant phage. Phage display allows for the identification of antiviral candidates, using a strategy which consists of an initial screening for target affinity, followed by confirmation of inhibitory potential on viral replication. After summarising previous uses of phage display in antiviral research, this review proposes optimized strategies for combining the significant screening potential of phage display with complementary rational approaches based on understanding interactions in, and structures of, viral complexes. Such combined strategies would maximise the selection of molecules with strong antiviral potential.
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http://dx.doi.org/10.1684/13-2.2021.14902 | DOI Listing |
Antibodies (Basel)
December 2024
Department of Pharmacology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA.
Background/objectives: Anterior Gradient-2 (AGR2/PDIA17) is a member of the protein disulfide isomerase (PDI) family of oxidoreductases. AGR2 is up-regulated in several solid tumors, including pancreatic ductal adenocarcinoma (PDAC). Given the dire need for new therapeutic options for PDAC patients, we investigated the expression and function of AGR2 in PDAC and developed a novel series of affinity-matured AGR2-specific single-chain variable fragments (scFvs) and monoclonal antibodies.
View Article and Find Full Text PDFProtein Sci
January 2025
Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Kyoto, Japan.
Antibodies and antibody mimics are extensively used in the pharmaceutical industry, where stringent safety standards are required. Implementing heat sterilization during or after the manufacturing process could help prevent contamination by viruses and bacteria. However, conventional antibodies and antibody mimics are not suitable for heat sterilization because they irreversibly denature at high temperatures.
View Article and Find Full Text PDFACS Appl Mater Interfaces
December 2024
Air Force Research Laboratory, 711th Human Performance Wing, Wright-Patterson Air Force Base, Wright-Patterson AFB, Ohio 45433, United States.
Peptides, due to their diverse and controllable properties, are used as both liquid and gas phase recognition elements for both biological and chemical targets. While it is well understood how binding of a peptide to a biomolecule can be converted into a sensing event, there is not the same mechanistic level of understanding with regard to how peptides modulate the selectivity of semiconductor/conductor-based gas sensors. Notably, a rational, mechanistic study has not yet been performed to correlate peptide properties to the sensor response for volatile organic compounds (VOCs) as a function of chemical properties.
View Article and Find Full Text PDFNat Commun
December 2024
Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya University, Nagoya, Japan.
Biologically produced protein drugs are generally susceptible to degradation by proteases and often exhibit immunogenicity. To address this issue, mirror-image peptide/protein binders consisting of D-amino acids have been developed so far through the mirror-image phage display technique. Here, we develop a mirror-image protein binder derived from a monobody, one of the promising protein scaffolds, utilizing two notable technologies: chemical protein synthesis and TRAP display, an improved version of mRNA display.
View Article and Find Full Text PDFNat Commun
December 2024
Institute of Physiological Chemistry, Faculty of Medicine, Philipps University of Marburg, Marburg, Germany.
Mirror-image proteins, composed of D-amino acids, are an attractive therapeutic modality, as they exhibit high metabolic stability and lack immunogenicity. Development of mirror-image binding proteins is achieved through chemical synthesis of D-target proteins, phage display library selection of L-binders and chemical synthesis of (mirror-image) D-binders that consequently bind the physiological L-targets. Monobodies are well-established synthetic (L-)binding proteins and their small size (~90 residues) and lack of endogenous cysteine residues make them particularly accessible to chemical synthesis.
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