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Engineered Nanoparticles for Drug Delivery in Cancer Therapy *
Published in Valerio Voliani, Nanomaterials and Neoplasms, 2021
Tianmeng Sun, Yu Shrike Zhang, Pang Bo, Dong Choon Hyun, Miaoxin Yang, Younan Xia
Rapid escape/release of nanoparticles from endolysosomes can also be induced when their surfaces are modified with a pH-sensitive peptide capable of physically interacting with endolysosomal membranes. GALA, a pH-sensitive fusion peptide composed of 30 amino acids with repeating units of glutamic acid-alanine-leucine-alanine, could perturb the lipid bilayer and facilitate nanoparticles to escape from endosomes at low pH values [150]. When the pH value decreased from 6 to 5 in the endosome, the negative charges on GALA decreased, causing a conformational change from random coil to amphipathic a-helix. This change allowed GALA to bind to the endosomal membrane, causing membrane disruption.
Torovirus
Published in Dongyou Liu, Handbook of Foodborne Diseases, 2018
Ziton Abdulrida Ighewish Al-Khafaji, Ghanim Aboud Al-Mola
Fusion proteins have to be produced in an inactive state in order to avoid triggering fusion in the Golgi or other compartments upon synthesis and transport to the cell surface. Many are activated in the trans Golgi network or at the cell surface by proteolytic cleavage, which reveals the fusion peptide.
Human Parainfluenza Virus Infections
Published in Sunit K. Singh, Human Respiratory Viral Infections, 2014
Eric T. Beck, Kelly J. Henrickson
The fusion (F) glycoprotein is one of two HPIV surface glycoproteins found on the mature HPIV virion (and also on the cell membrane of infected host cells).34–36 The F protein is a type I glycoprotein that has several important functions in the viral life cycle. The most conserved portion of the F protein, the fusion peptide, is located at amino acids 110–135 of HPIV-3 (and is similarly located in other Paramyxoviruses). The high level of protein conservation (as well as the hydrophobicity and alpha helical configuration) indicate that the fusion peptide is likely involved in membrane insertion, leading to viral/host cell fusion.5 This hypothesis is further supported by the facts that (1) cleavage events in the immature F protein work to expose the fusion peptide and increase its hydrophobicity, (2) synthetic peptides mimicking the fusion peptide of Paramyxoviruses can inhibit viral fusion, and (3) site-specific mutations expected to increase the alpha helical nature of the fusion peptide also increase the fusogenicity of the virus.37–42 The F protein also plays a role in syncytia formation when active F protein molecules on the surface of infected cells cause neighboring cells to fuse.
Exploring Klebsiella pneumoniae capsule polysaccharide proteins to design multiepitope subunit vaccine to fight against pneumonia
Published in Expert Review of Vaccines, 2022
Jyotirmayee Dey, Soumya Ranjan Mahapatra, S Lata, Shubhransu Patro, Namrata Misra, Mrutyunjay Suar
In the process of epitope selection, only peptides that were conserved across B and T cells, and that exhibited high antigenicity score, non-allergenic, nontoxicity, binding to the maximum number of HLA alleles were selected for further analysis. To construct the vaccine, antigenic epitopes were fused with the help of specific peptide linkers. In the next step, adjuvant was selected based on a literature study to develop the effectiveness of the vaccine. While choosing an adjuvant, characteristics such as hydrophilicity, hydrophobicity, hydropathicity, isoelectric point (pI), and salvation were considered. One of the key issues with the design of peptide vaccine is its weak immunogenicity that can be resolved by designing a multi-epitope vaccine with appropriate adjuvant [27]. Additionally, the selected CTL, HTL, and B-cell epitopes were added to form a fusion peptide using KK, GPGPG, and AAY peptide linkers at specific positions. Adjuvant was attached to the linear B-cell epitopes with the help of the EAAAK linker. The linkers have a dual function, for the separation of epitopes to avoid neo-epitopes (junctional epitopes) formation and enhance the presentation of epitopes. Thus, linkers are helpful for differentiation and improvement of epitope presentation [28,29].
Evolution of A(H1N1) pdm09 influenza virus masking by glycosylation
Published in Expert Review of Vaccines, 2021
HA primarily function is the determinant of receptor binding specificity and mediates membrane fusion. Different amino acids sites in different subtypes of HA play various roles in binding specific receptors. The required changes in binding specificity occur through mutations that create less polar environments in the binding regions occupied by the sialic acid-galactose (Gal)-2 linkage. For H1 viruses, mutations of E190D and G225D, with consequently loss of hydrogen bond network, promotes the affinity transfer from SA α2,3 Gal to SA α2,6 Gal, whereas mutations at site Q226L and G228S are the key for H2 and H3 viruses to effectively bind to SA α2,6 Gal [20], lead polar to nonpolar changes. Virus is taken into cells by endocytosis after binding to a receptor. When exposed to low pH environment, the HA protein undergoes an irreversible conformation change from its metastable prefusion conformation to a hairpin structure involving extrusion of the fusion peptide from the interior of the HA2, promoting fusion of the viral and endosomal membranes [21,22]. The interaction between fusion peptide and the target membrane leads to an extended intermediate that bridges the viral and cell membranes [23]. The fusion process allows the release of viral ribonucleocapsid into cytoplasm of an infected cell, leading to the accomplishment of the entry step. Extensive rearrangement of residues in HA2 have been demonstrated by X-ray crystallographic studies, that at lower pH along with respect to their relative orientation and coil-coil formation, helix-to-loop or loop-to-helix transitions [24–26].
Searching for effective antiviral small molecules against influenza A virus: A patent review
Published in Expert Opinion on Therapeutic Patents, 2021
Tiziana Ginex, F. Javier Luque
The infection is triggered upon binding of HA to the sialic acid residues in glycoconjugates attached to the host-cell membrane (Figure 1). This process is assisted by the sialidase activity of NA, which permits to suppress nonproductive and scan the cell surface for productive binding with sialylated receptors [28, 29]. HA-mediated binding to the receptor triggers endocytosis of the virion. In the interior of the endosome, the low pH causes a large-scale conformational in HA that involves multiple steps, including cleavage of HA by host-cell proteases into two subunits, HA1 and HA2. This process releases the fusion peptide and ultimately promotes the fusion of both viral and host-cell membranes. On the other hand, the M2 channel transports protons to the interior of the virus, which facilitates the disassembly of the packaged vRNPs from M1, thus enabling their transfer to the host cytoplasm following HA-mediated fusion.