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Order Mononegavirales
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
In parallel, the development of the filoviral vaccine strategy focused on the VLP approach, as indicated in Table 31.1. The EBOV and MARV VLPs composed of the glycoprotein GP and matrix protein VP40 and resembling the distinctively filamentous infectious virions were generated by the expression in mammalian cells (Bavari et al. 2002). The vaccination of rodents with EBOV (Warfield et al. 2003) or MARV (Swenson et al. 2004) VLPs conferred induction of the immune response and protected mice against EBOV (Warfield et al. 2003) or guinea pigs against MARV (Warfield et al. 2004) lethal challenge. Further, EBOV and MARV VLPs were shown to be more effective stimulators of human dendritic cells than the respective viruses (Bosio et al. 2004). A pan-filovirus hybrid VLP vaccine candidate based on EBOV and MARV proteins GP and VP40 demonstrated that only GP was required and sufficient to protect against a homologous filovirus challenge (Swenson et al. 2005). Moreover, the EBOV and MARV VLPs produced in mammalian cells fully protected nonhuman primates (cynomolgus macaques) from the lethal viral challenge (Warfield et al. 2007b). Finally, it was concluded that the expression of the matrix protein VP40 alone is sufficient for VLP production, but addition of other filovirus proteins increases the efficiency of VLP production in mammalian cells and results in the case of the coexpression of GP and VP40 in the promising vaccine candidate (for a full list of references, see review by Warfield et al. 2005 and Warfield and Aman 2011). Later, the VLPs consisting of NP, GP, and NP40 of lloviu cuevavirus of the genus Cuevavirus were prepared (Maruyama et al. 2014). The modified vaccinia Ankara (MVA) vaccine platform was used to generate the EBOV (Schweneker et al. 2017) and MARV (Malherbe et al. 2020) VLPs and demonstrate their protective effect in animals. Similarly, the MARV GP+NP40 VLPs were produced by the pox virus-based platform (Lázaro-Frías et al. 2018).
Virus
Published in Joseph R. Masci, Elizabeth Bass, Ebola, 2017
Joseph R. Masci, Elizabeth Bass
Ebola virus appears under electron microscopy as a pleomorphic filamentous structure, which varies in length from 300 to 1500 nm (Murphy et al. 1978) with a diameter of approximately 80 nm. The filaments, which are indistinguishable from those of Marburg virus, may form U shaped or circular structures (Bowen et al. 1977; Johnson et al. 1977; Pattyn et al. 1977; Murphy et al. 1978). The virus consists of a lipid envelope that is derived from host membranes containing glycoprotein protrusions. This envelope surrounds a matrix of VP40 and VP24 proteins and a 40–50 nm nucleocapsid containing the viral proteins VP30, VP35, NP, and L. These proteins function as follows (Sanchez et al. 1993): Nucleoprotein (NP): Necessary for the formation of nucleocapsid structures.VP35: Structural protein of the nucleocapsid. Necessary for replication and transcription. Also functions to block the effect of host interferon and antiviral activity.VP24: Along with NP and VP35 forms the nucleocapsid. It binds to the plasma membrane in infected host cells and has a role in virion assembly. Also, suppresses host antiviral activity.VP40: The most abundant viral protein. Determines viral configuration and is essential for viral budding from host cells.VP30: A constituent of the nucleocapsid along with VP 24 and NP. Also has a role in initiation of transcription.ZEBOV L protein: An RNA-dependent RNA polymerase and the largest protein in the virus. Together with VP35, it transcribes and replicates the genome.GP precursor: Forms the glycoproteins (GP1, 2, soluble GP [sGP] and small soluble GP [ssGP]) and, thus, the peplomers in the viral envelope.
Antiviral Nanomaterials in Therapeutic Interventions
Published in Devarajan Thangadurai, Saher Islam, Charles Oluwaseun Adetunji, Viral and Antiviral Nanomaterials, 2022
Karan Chaudhary, Dhanraj T. Masram
GC et al. (2017)investigated interactions of graphene with protein VP40 of Ebola virus matrix by utilising molecular dynamics simulations and graphene pelleting assay. There exist several oligomeric and conformational forms of VP40 protein and, for disrupting the life cycle of the Ebola virus, it is a potential target. The result shows a strong association of graphene at various interfaces of protein, and graphene disrupts the CTD-CTD interface that is vital in forming the matrix of the Ebola virus. This study shows the potential of graphene nanomaterials because their solutions may be used as disinfectants to prevent the disease spread by the Ebola virus (GC et al. 2017). Yang et al. (2017) synthesised GO composite with excellent antiviral activity against respiratory syncytial virus (RSV). The composite material used had curcumin loaded on β-cyclodextrin functionalized GO. This composite material also had great biocompatibility with host cells. Studies showed that GO composite inhibited RSV infection by three possible mechanisms: direct inactivation of the virus, inhibiting the attachment of RSV with the host cells, and interference with the replication of virus. Against RSV, composite material had prophylactic and therapeutic effects (Yang et al. 2017). Du et al. (2018b) used GO modified with silver NPs against porcine reproductive and respiratory syndrome virus (PRRSV). Results showed that nanocomposite suppressed the viral infection with an inhibition efficiency of 59.2%. Further, production of IFN-stimulating genes and interferon-α was enhanced by the nanocomposite that can directly prevent the virus proliferation (Du et al. 2018b). Donskyi et al. (2019) prepared numerous derivatives of triazine-functionalized graphene using fatty amines and polyglycerol sulfate and studies antiviral activity against herpes simplex virus type-1 (HSV-1) through interactions. Graphene derivatives bind to the virus through electrostatic interactions between the virus and polyglycerol sulfate. Conversely, antiviral activity of graphene derivatives is due to secondary hydrophobic interactions of alkyl chains. Among various graphene derivatives, the derivative having an alkyl chain with 12 carbon atoms displayed the highest activity, but for the Vero cell line, it was toxic. Further, graphene derivatives with alkyl chain length of 6 and 9 carbon atoms showed antiviral activity with low toxicity. Therefore, this study demonstrated that stepwise and controlled functionalization of graphene could be used for the development of antiviral agents against HSV-1 (Donskyi et al. 2019).
Targeting Ebola virus replication through pharmaceutical intervention
Published in Expert Opinion on Investigational Drugs, 2021
Frederick Hansen, Heinz Feldmann, Michael A Jarvis
RNPs are subsequently transported to the cell surface in an actin-dependent manner [51,52]. In parallel, the matrix protein VP40 is also transported to the cell surface, where it interacts with cellular trafficking system components such as actin and microtubules [53–56]. The filovirus GP moves to the cell surface through the secretory pathway, where it is post-translationally modified by O- and N-linked glycosylation [57] and furin cleavage into the mature GP1 and GP2 subunits [58]. Finally, VP40 coordinates virion assembly and budding at the plasma membrane supported by host factors such as those of the endosomal complex required for transport (ESCRT) and ubiquitin ligases, which interact with VP40 through its late-domain motifs [59–62]. GP1,2 was shown to facilitate the trafficking of host scramblases to sites of virion budding, thereby enhancing exposure of PtdSer on the outer envelope of virions for binding to PtdSer receptors such as TIM-1 during entry [63].
The role of plant expression platforms in biopharmaceutical development: possibilities for the future
Published in Expert Review of Vaccines, 2019
While ZMAPP antibodies offer one strategy to protect against Ebola infection, a plant-made vaccine would also be useful. Tobacco plants have been developed which produce the VP40 antigen from the Zaire Ebola virus [38]. Constructs contained a signal peptide to access the endoplasmic reticulum, enabling VP40 to reach levels as great as 2.6 µg/g fresh weight in leaf tissue. Purified extracts provided retained antigenicity and induced immune responses in BALB/c mice following three weekly oral or subcutaneous immunizations at low dosages (12.5 and 25 ng, respectively). Furthermore, these immunogenicity studies require no need for adjuvants, demonstrating the ease of utilization of a plant-made vaccine to combat Ebola virus disease outbreaks. A multitude of other designs for a plant-made vaccine to Ebola virus have also been described [39].
Ebola vaccine trials: progress in vaccine safety and immunogenicity
Published in Expert Review of Vaccines, 2019
Keesha M. Matz, Andrea Marzi, Heinz Feldmann
Structurally, ebolaviruses appear as enveloped filamentous particles [3,6,9]. As a typical mononegavirales, they possess a single-stranded negative-sense non-segmented RNA genome. The genome is encapsidated by the nucleoprotein (NP) and associated with the polymerase (L), the polymerase co-factor viral protein (VP35) and the transcriptional activator VP30 which altogether make up the nucleocapsid. This structure is associated with VP24 and surrounded by the matrix protein, VP40. The transmembrane glycoprotein (GP) is a class 1 fusion protein and forms trimeric spikes on the outside of the virion envelope. It displays receptor-binding and fusion functions and, thus, is essential for virus entry into the cell. Since GP is an important target for the host immune response, it has been the main viral component for vaccine development.