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Order Martellivirales: Bromoviridae
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
Smith et al. (2000) resolved the crystal structure of cucumber mosaic virus (CuMV) to 3.2 Å. This structure is presented in Figure 17.3. Despite the fact that CuMV has only 19% coat identity and 34% similarity to CCMV, the core structures of these two members of the Bromoviridae family are highly homologous. In CCMV, the structures of the A, B, and C subunits are initially identical except in their N termini. In contrast, the structures of two loops in subunit A of CuMV differ from those in B and C. Unlike that of CCMV, the capsid of CuMV does not undergo swelling at pH 7.0 and is stable at pH 9.0. This may be partly due to the fact that the N termini of the B and C subunits form a unique bundle of six amphipathic helices oriented down into the virion core at the threefold axes. In addition, while CCMV has a cluster of aspartic acid residues at the quasi-threefold axis that is able to bind metal in a pH-dependent manner, this cluster is replaced by complementing acids and bases in CuMV (Smith et al. 2000).
Terpenes: A Source of Novel Antimicrobials, Applications and Recent Advances
Published in Mahendra Rai, Chistiane M. Feitosa, Eco-Friendly Biobased Products Used in Microbial Diseases, 2022
Nawal M. Al Musayeib, Amina Musarat, Farah Maqsood
Ketonic monoterpenes and monoterpenes containing aldehydes were found to possess potent antimicrobial activities due to their high electronegativity created by carbon double bond arrangements in their structure (Smid et al. 1995). Based on this observation, reported that nine monoterpenes including α-pinene, α-terpinene, α-terpineol, γ-terpinene, δ-cymene, 1, 8-cineole, thymol, terpinen-4-ol, and citral showed antimicrobial potential against Herpes Simplex Virus type 1 (HSV-1). Dunkic et al. (2010) listed a few more monoterpenes (1, 8-cineole, borneol, thujone, bornyl acetate, isoborneol and camphor) displaying a considerable effect against HSV-1. Carvacrol and thymol were also reported to exhibit a powerful antimicrobial effect against the Tobacco mosaic and Cucumber mosaic virus.
Biodiscovery of Marine Microbial Enzymes in Indonesia
Published in Se-Kwon Kim, Marine Biochemistry, 2023
Ekowati Chasanah, Pujo Yuwono, Dewi Seswita Zilda, Siswa Setyahadi
Carrageenan is a sulfated polysaccharide that is an important component in the cell walls of red seaweeds. Carrageenan has been commercially produced and used as gelling, thickening, and stabilizing agents in the food industry and others, and their derived products, namely, oligosaccharides, have been reported to be active against tumors and viruses and are rich in antioxidant and immunomodulation activities. Therefore, carrageenan oligosaccharide has a significant potential for biomedical and physiological applications. It has various important applications, such as bioethanol production, textile industry, as a detergent additive and for isolating the protoplast of algae (Chauhan & Arunika, 2016; Gui, Gu, Zhang, & Li, 2021). The enzymes that are involved in biologically producing oligosaccarides are kappa (κ-), iota (ι-) and lambda (λ-) carrageenases. They are endohydrolaze enzymes that hydrolyze β-(1–4) linkages of carrageenans internally, yielding oligo-carrageenan products. From sediment of a hot spring of Lampung, Indonesia, a κ-carrageenase had been reported to be produced by carrageenan-degrading bacterium Bacillus sp. HT19. The purified enzyme works best at 60°C and a pH of 7.0. The product hydrolysate was neo-carrabiose that has been reported can improve the cucumber against cucumber mosaic virus and increased the activity of antioxidant enzymes in infected plants (Li, Pan, Xie, Zhang, & Gu, 2018). Carrageenan degrading enzymes or carrageenases was detected from bacteria associated with Kappahycus alvarezii namely Labrenzia sp., Alteromonas sp., Vibrio sp., Celeribacter sp., Pseudoalteromonas sp., Phaeobacter sp. and Cobetia sp. (Yusriyyah, Citra, Tassakka, & Latama, 2021). Vibrio, which are marine bacteria, are also reported to produce carrageenase. A Vibrio sp. strain NJ-2 isolated from rotten red algae secreted carrageenase with a molecular mass of 33 kDa and worked best at 40°C and a pH of 8.0. At optimum conditions, the enzyme showed a maximal activity of 937 U/mg and hydrolyzed the κ-carrageenan into 2–8 unit of D-oligosaccharides (Zhu & Ning, 2016).
New generation of viral nanoparticles for targeted drug delivery in cancer therapy
Published in Journal of Drug Targeting, 2022
Nikta Alvandi, Maryam Rajabnejad, Zeynab Taghvaei, Neda Esfandiari
VLPs are unable to replicate and this feature can be regarded as a marked difference between VLPs and native viruses [20]. Moreover, VLPs structure can be changed by nucleic acid template modification and the addition of conjugates to particular amino acids. It is patently obvious that the nucleic acids of viruses are enclosed in capsid which includes various copies of identical coat proteins [21]. The capsid of viruses can be classified into two shapes, icosahedral and helical structures. Flexible filaments and rod shapes can be regarded as helical structures. The common and important viruses as candidates of each category based on their shapes are reported in Figure 2(A). Brome mosaic virus (BMV), cucumber mosaic virus (CMV), cowpea mosaic virus (CPMV), cowpea chlorotic mottle virus (CCMV), and bean yellow dwarf virus (BeYDV) are reported as plant virus-based VLPs with icosahedral symmetry. It should be noted that potato virus X (PVX) [22] and tobacco mosaic virus (TMV) are famous and significant plant viruses with filamentous and tubular structures, respectively [23]. Concerning bacteriophage viruses, Qβ, MS2, P22 with icosahedral symmetry, and M13 phage with filamentous shape is considered as well-known bacteriophage-based VLPs. Furthermore, animal viruses can be categorised into mammalian and insect viruses. Adenovirus, human papillomavirus (HPV) [24], norwalk virus (NV), hepatitis B virus (HBV), rotavirus A, enterovirus, influenza virus [25], human immunodeficiency virus (HIV), and human parvovirus as mammalian virus-based VLPs along with baculovirus known as insect virus-based VLPs can be considered in icosahedral symmetry category too [26]. In the term of VLPs structure, VLPs can be divided into non-enveloped and enveloped VLPs according to their origin viruses which VLPs were emerged from them. Generally, some of the viruses have an envelope that surrounds their capsid. It is common knowledge that an envelope is a lipid membrane derived from the host cell membrane. Depending on different types of viruses, their envelope can come from the membrane of different organelles of mentioned host cells, such as endoplasmic reticulum, Golgi complex, and so on. It should be noted that viruses that possess envelope also have matrix proteins which connect envelope to their capsid (Figure 2(B)) [27].
Deciphering Vaccines for COVID-19: where do we stand today?
Published in Immunopharmacology and Immunotoxicology, 2021
Tushar Baviskar, Dezaree Raut, Lokesh Kumar Bhatt
VLP are nanostructures that are identical to the structure of the virus. They consist of few or all the proteins that are involved in the structure of the viral capsid but lack the genetic material that is responsible for the transmission of disease. Due to lack of genetic material, VLPs are not capable of replicating in the recipient but they trigger the immune system by recognizing the repetitive subunits and produces high cellular and humoral immune responses [56]. Various pre-clinical and clinical studies suggest that various recombinant VLP and nanoparticle vaccines are promising candidates against respiratory viruses [57]. Zha et al. showed that the recombinant RBD of the S protein homologous to SARS binds to ACE-2. Immunologically optimized VLP derived from cucumber mosaic virus resulted in a vaccine candidate (RBD-CuMVTT) which has a highly repetitive display of RBD. It induced the production of highly specific antibodies in mice capable to prevent the binding of S protein to ACE-2 and neutralize the SARS-CoV-2 virus in vitro [58]. Medicago, a biopharmaceutical company successfully produced VLP of SARS-CoV-2 using its proprietary plant-based technology [59]. Single-dose administration of this vaccine in mice showed a positive antibody response 10 days post-administration [60]. A randomized, partially-blinded, prime-boost, staggered dose-escalation Phase 1 study is in progress to evaluate the Comet safety, tolerability, and immunogenicity of the Coronavirus-Like Particle COVID-19 [28]. VBI Vaccines Inc. is developing a vaccine using its enveloped virus-like particle platform (eVLP) as reports suggest that the coronaviruses are enveloped in nature. VBI collaborated with the National Research Council of Canada for the development of a pan-coronavirus experimental vaccine candidate, for targeting COVID-19, SARS, and MERS. They expect to develop a multivalent eVLP vaccine candidate that will co-express SARS-CoV-2, SARS-CoV, and MERS-CoV S proteins on the same particle. Also, it is expected that the trivalent construct may allow the production of broad-spectrum antibodies, that will protect from mutated strains of the COVID-19 that may emerge in the future [61]. According to WHO, seven different vaccine candidates are under development on the VLP platform [12]. Vaccine candidates from this category in the clinical trials are enlisted in Table 1.
The 5th virus-like particle and nano-particle vaccines (VLPNPV) conference
Published in Expert Review of Vaccines, 2019
Paul Engeroff, Martin F. Bachmann
Allergic inflammation is caused by typically harmless substances that trigger hypersensitivity of the immune system through induction of TH2 cytokines and IgE antibodies that cause degranulation of allergic effector cells such as mast cells and basophils [19]. Several projects were presented that aim to treat allergic inflammation by using VLP-based vaccination approaches. Matthew Heath (Allergy Therapeutics, Worthing, UK) presented preclinical data on a vaccine candidate for peanut allergy. Cucumber Mosaic Virus (CuMV) particles were coupled with the major peanut allergens Ara h 1 or Ara h 2. In a mouse model of peanut allergy, vaccination with the CuMV-Ara h1 vaccine resulted in complete protection from peanut extract challenge. Interestingly, the vaccines did not induce anaphylaxis in peanut extract sensitized mice. This mechanism was further elaborated on by Paul Engeroff, (University of Bern, Bern, Switzerland) who showed with the example of Qβ VLP that allergens coupled to VLPs enhances their immunogenicity but inhibits their potential to activate IgE sensitized human mast cells. The fact that VLPs fail to trigger allergic effector cells is promising since conventional allergen-specific immunotherapy relies on unmodified allergens that pose a significant risk of side effects due to the potential of triggering effector cells [20]. Another approach of intervening with allergic inflammation is eliminating the cytokines that result in the recruitment of effector cells. Martin Bachmann (University of Bern, Bern, Switzerland) presented CuMV-based vaccines targeting IL-31 in dogs. IL-31 is a major cytokine driving atopic dermatitis which is the most common allergic disease in dogs, causing local itching, scratching and thereby hair loss. Canine IL-31 was coupled to CuMV and Vaccination against IL-31 induced IL-31-specific IgG titers and resulted in a reduction of scratching activity in dogs [21]. Martin Bachmann showed further data where the same vaccination approach was used to successfully target equine IL-5 for treating insect bite hypersensitivity in horses [22]. The same principle was also described by John Foerster (University of Dundee, Dundee, Scotland, UK) who described a promising CuMV-based vaccine targeting IL-17 in a mouse model of the chronic autoimmune disease Psoriasis. VLP-based vaccines could also be used for the treatment of chronic pain, which posts a high socioeconomic burden as it affects one in five people and current analgesics are limited in efficacy, tolerability and have abuse potential. Nerve-growth factor (NGF) represents a novel therapeutic target in chronic pain [23] and Aadil Turabi (University of Oxford, Oxford, UK) showed that a VLP-based vaccine targeting NGF can alleviate pain in mice.