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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
In parallel with the structure of BMV (Lucas et al. 2000b), Lucas et al. (2002a) solved the 3D structure of tomato aspermy virus (TAV), a member of the Cucumovirus genus, to 4 Å. The TAV particle of 28 nm in diameter had the canonical β-barrel topology with a distinctive N-terminal α-helix directed into the interior of the virus where it interacted with encapsidated RNA. The N-terminal helices were joined to the β-barrels of protein subunits by extended polypeptides of six aa residues, which served as flexible hinges allowing movement of the helices in response to local RNA distribution. The side chains of Cys64 and Cys106 formed the first disulfide observed in a cucumovirus, including a unique cysteine, 106, in a region otherwise conserved. A positive ion, putatively modeled as a Mg2+ ion, lay on the quasi-threefold axis surrounded by three quasi-symmetric Glu175 side chains (Lucas et al. 2002a).
Replicase
Published in Paul Pumpens, Single-Stranded RNA Phages, 2020
Watanabe et al. (1968a) looked for the specific inhibition of the Qβ replicase, in comparison with the DNA-dependent RNA polymerase from E. coli. Some chemical compounds, as ethine derivatives, demonstrated strong inhibitory effect on Qβ replicase, while no such specific agent was found among 13 kinds of well-known antibiotics, including rifamycin and chromomycin A3, although pluramycin had some inhibitory effect. This study was continued further with about 1000 synthetic chemical compounds, and the inhibitory effect of the ethine derivatives was acknowledged (Haruna et al. 1970). Furthermore, tobacco mosaic virus (TMV) RNA was found as a specific natural inhibitor of Qβ replicase, while other tested RNAs, including phage, animal and plant viruses, E. coli, and yeast RNAs, were inert (Okada et al. 1969). The binding of the TMV RNA to the Qβ enzyme, but not to the Qβ RNA, was directly demonstrated by retention of the RNA-enzyme complex on a nitrocellulose filter, whereas the relative affinity of the Qβ enzyme to TMV RNA was comparable to that for Qβ RNA (Okada et al. 1971). Once the Qβ synthesis had started, however, the reaction was not inhibited by TMV RNA during the chain growth reaction. Moreover, the Qβ replicase reaction was inhibited by fragmented Qβ RNA when Qβ RNA was heated at a high temperature before reaction (Yamane et al. 1973). Both Qβ and SP replicases were inhibited specifically by the tomato aspermy virus particles (Okada and Haruna 1969).
Hyaluronan-based delivery of therapeutic oligonucleotides for treatment of human diseases
Published in Expert Opinion on Drug Delivery, 2019
Interesting three components supramolecular assembly was realized when siRNA was complexed with 2b protein and the obtained complex was loaded into pre-formed HA nanogel (Figure 2(f)) [61]. It was reported that 2b proteins, derived from Tomato aspermy virus, neutralize the negative-charged phosphate backbone of siRNA when they wrap around the siRNA duplex [62]. Amphiphilic cholesterol-modified HA (HA-Chol) self-assembled in aqueous solution and acted as a container for the neutralized 2b/siRNA complex (Figure 2(f)). One can envisage both hydrophobic and electrostatic interactions between the HA nanogel and 2b/siRNA complex. The fact that zeta potential of the loaded nanogel (−44.2 mV) was only slightly higher than that for the parent HA-Chol conjugate (−45.1 mV) indicates that 2b/siRNA complex was loaded primarily owing to hydrophobic interactions.