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Order Bunyavirales
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
The single-cycle virus-like-particles vehicles or vectors (VLPVs) are employing encapsulated alphavirus replicons expressing foreign gene(s) of interests, as reviewed by Pushko and Tretyakova (2014). The alphavirus RNA replicon technology provided a reasonable compromise, in terms of safety and immunogenicity, between live-attenuated and inactivated vaccines. The vaccine particles prepared by this technology are not able to spread beyond the initially infected cells but can efficiently deliver and transduce the gene(s) of interest into target cells (e.g., dendritic cells, DCs). This vaccine technology was based usually on an attenuated strain of Venezuelan equine encephalitis virus (VEEV) (Pushko et al. 1997), and numerous alphavirus replicon-based vaccine candidates reached preclinical and clinical development (Pushko and Tretyakova 2014).
Arthropod-borne virus encephalitis
Published in Avindra Nath, Joseph R. Berger, Clinical Neurovirology, 2020
First isolated from the brains of horses during an epizootic in Venezuela in 1936, Venezuelan equine encephalitis virus (VEEV) was the third equine encephalitis virus to be identified [113,114]. However, outbreaks had been recorded since the 1920s. Since that time, VEEV disease has presented dramatic contrasts: It can be manifested as a brief dengue-like illness or as a severe encephalitis; it has seasons in which it produces massive epizootics and epidemics in which tens of thousands of horses and people become ill followed by years in which no epizootic/epidemic activity is found [115].
Current Inhibitors of Dengue Virus
Published in Venkatesan Jayaprakash, Daniele Castagnolo, Yusuf Özkay, Medicinal Chemistry of Neglected and Tropical Diseases, 2019
J. Jonathan Harburn, G. Stuart Cockerill
Compound 5-3 was identified from a screen of a 200,000 compounds diversity selection. Hits were evaluated in a cytopathic effect assay at 5 μM (Byrd et al. 2013). 5-3 was subsequently evaluated in a whole virus plaque assay and found to inhibit all 4 serotypes of the virus at sub micromolar levels and was also shown to be specific for flaviviruses. Moderate activity was observed for yellow fever virus (7.4 μM) and Venezuelan equine encephalitis virus (10.1 μM, of the family Togaviridae).
The Ebola virus glycoprotein and its immune responses across multiple vaccine platforms
Published in Expert Review of Vaccines, 2020
Venezuelan equine encephalitis virus (VEEV) is an Alphavirus and a member of the Togaviridae family. VEEV has a non-segmented, positive-sense RNA genome with two open reading frames. The production of virus-like replicons is done by replacing VEEV genes with the viral antigen of interest; in the case of EBOV, this is primarily GP because of the robust humoral response associated with it. The replacement of VEEV genes with that of the antigen of interest also limits the replicon to a single round of infection while maintaining ample protein expression for the gene of interest [47,48]. While VEEV with EBOV GP is the most antigenic construct, other replicons have been generated to include NP, VP24, VP30, VP35, and VP40. Investigation into the cellular response to GP in a replicon system did not produce favorable results; only one epitope of GP produced a response in CD8+ T cells and those positive cells were not cytolytic, indicating they are most likely not part of the immune response conferring protection in NHPs [49]. The humoral response remains to be the dominate immune response elicited by the replicon system in NHPs (Figure 1) [50].
Poxvirus-based vector systems and the potential for multi-valent and multi-pathogen vaccines
Published in Expert Review of Vaccines, 2018
Natalie A. Prow, Rocio Jimenez Martinez, John D. Hayball, Paul M. Howley, Andreas Suhrbier
An alternative to mixing a series of immunogens/antigens or vectors encoding single immunogens (Table 4) is the generation of single vector construct, multi-immunogen vaccines. So far the number of licensed and registered recombinant (or genetically modified) virally vectored vaccines for human use is rather low, with Dengvaxia® being the first and only current example [70]. A number of vaccine vector systems are potentially suitable for multi-valent and/or multi-pathogen vaccines [14,15,71], e.g. bacterial platforms [72], vesicular stomatitis virus (VSV) [73], varicella [74] and adenovirus [75]. However, poxvirus systems have the relatively unique capacity for large recombinant inserts [22] and have thus been widely used for development of multi-valent vaccines (Tables 1, 2, and 3). A large number of rMVA vaccines are in advanced clinical trials and many are multi-valent vaccines encoding multiple immunogens, with one rMVA multi-pathogen vaccine also in phase 1 human clinical trials (Table 2, MVA-BN-Filo). A mixed multi-pathogen rMVA vaccine targeting western equine encephalitis virus (WEEV), eastern equine encephalitis virus (EEEV) and Venezuelan equine encephalitis virus (VEEV) (Table 4) is also soon to enter clinical trials. A single-construct SCV-ZIKA/CHIK vaccine targeting ZIKV and CHIKV (viral pathogens from different viral families) is described above (and in Table 3, Figures 1 and 2).
Quinazoline and quinazolinone as important medicinal scaffolds: a comparative patent review (2011–2016)
Published in Expert Opinion on Therapeutic Patents, 2018
Abdul Hameed, Mariya Al-Rashida, Maliha Uroos, Syed Abid Ali, Marium Ishtiaq, Khalid Mohammed Khan
Venezuelan Equine Encephalitis Virus (VEEV), is known to cause severe neurological disorders in both humans and horses. The disease in humans is characterized by fever, headache, and encephalitis to varying degree and is sometimes fatal. The mortality rate is 1%; however, the neurological disease is present in up to 14% of the patients. The virus is typically transmitted through mosquito bite, but evidence supports viral transmission by aerosol as well. This mode of transmission makes VEEV infection very difficult to control during outbreaks. Thus, prophylaxis and efficacious treatments are critical to minimizing the impact of the transmissible disease. Some 6-substituted quinazolinones were synthesized that acted through a post-entry, viral specific, mechanism of action by inhibiting viral replication through the nsP2 helicase, resulting in the prevention or treatment of diseases related to an encephalitic alpha virus. ‘Virus specific,’ that is the compounds do not use host cellular machinery to inhibit virus. Thus there are fewer off-target effects because the compounds only target the virus and not host. The synthetic compound may be administered to the lungs by inhalation through the nose or mouth. Suitable pharmaceutical formulations for inhalation include solutions, sprays, dry powders, or aerosol containing any appropriate solvent. The compounds (96–102) in Scheme 10 showed most promising antiviral activity [33].