Architecture and biogenesis of plus-strand RNA virus replication factories. A cluster of acute flaccid paralysis and cranial nerve dysfunction temporally associated with an outbreak of enterovirus D68 in children in Colorado, USA. Both viral proteins and host proteins essential for virus replication can be used as targets for virus inhibitors. The only EV protease inhibitors that have made it to clinical studies are the 3C pro inhibitors rupintrivir also known as AG , and AG also known as compound 1. In addition to treating infected patients, antiviral drugs might aid in the eradication of PV by helping to contain VDPV outbreaks and by treatment of immunodeficient patients who are chronically shedding PV. This mechanism is reminiscent of the release of hepatitis A virus, another picornavirus, which was recently shown to be released as membrane-wrapped virus particles in membrane structures resembling exosomes [ ]. Dual infections during the outbreak are not completely surprising in view of the high EV-D68 incidence during the outbreak Dyrdak et al.
The other class of polymerase inhibitors encompasses the non-nucleoside inhibitors. The poliovirus replication machinery can escape inhibition by an antiviral drug that targets a host cell protein. In vitro activity of pleconaril and AG against selected serotypes and clinical isolates of human rhinoviruses. Worldwide vaccination schemes started in have managed to reduce the incidence of PV enormously, but not completely [ 44 ]. In contrast, most variation below 0. In addition to the common cold, RVs can cause severe lower respiratory tract infections, such as pneumonia and bronchiolitis [ 5 ]. Though the t-butyl ether modification may be responsible for the inactivity of SG85 against HPeV 3C pro , this suggests that differences in cleavage sites alone cannot completely explain the disparity between the susceptibilities of the EV and HPeV 3C proteases to rupintrivir and SG
Effect of intravenous solvong for neonates with severe enteroviral infections with emphasis on the timing of administration. Morphogenesis of enteroviruses and targets for assembly inhibitors. The study provides a comprehensive proglem of the intra- and interpatient evolution of EV-D68, including the first report of intrapatient diversity and dual infections. The clinically most important genera are depicted. Virus replication can be impaired by targeting either viral proteins or host factors that are required for virus replication.
Epidemiology and Prevention of Vaccine-Preventable Diseases.
To control for such artifacts, we processed two high-titer patient samples in duplicate see Section 2. Discovering cellular targets by neural networks.
Replication and Inhibitors of Enteroviruses and Parechoviruses
This article has been cited by other articles in PMC. A screen shot is displayed in Fig. Structure-based problrm of Michael acceptor inhibitors and their broad-spectrum antiviral effects against picornaviruses.
Published online Apr Rhinovirus C and respiratory exacerbations in children with cystic fibrosis. Interestingly, the tree indicated that the B3 subclade did not evolve directly from the B1 subclade. Binding of glutathione to enterovirus capsids is essential for virion morphogenesis.
In contrast, most variation below 0. Enterovirus and Parechovirus Associated Diseases 1. Failure to demonstrate synergy between interferon-alpha and a synthetic antiviral, enviroxime, in rhinovirus infections in volunteers.
Picornavirus and enterovirus diversity with associated human diseases. Human rhinovirus C infections mirror those of human rhinovirus A in children with community-acquired pneumonia.
Even though EV-D68 was rarely reported before the recent outbreaks, a high prevalence of neutralizing antibodies have reported in samples collected before Vogt and Crowe Architecture and biogenesis of plus-strand RNA virus replication factories. A tangle-tree analysis suggested recombination within subclades, but not between clades or subclades Supplementary Fig.
Ribavirin–current status of a broad spectrum antiviral agent. The cycling profile was: On the other hand, SG85 contains a t-butyl ether of serine at P3, and a serine has been observed at this position in HPeV cleavage sites . Pleconaril displays broad-spectrum activity against most, but not all EVs and had some beneficial effects in clinical trials [,], but was rejected by the FDA in for the treatment of the common cold due to safety issues [ ].
These latter proteins are membrane-shaping proteins that induce and stabilize positive membrane curvature, and may be involved in the formation of the positively curved membranes that are essential for the morphogenesis of the viral replication organelles. Inhibitors of rhinovirus multiplication. Instead, the most recent ancestor of both clades was dated to Inhibition of enterovirus 71 replication and the viral 3D polymerase by aurintricarboxylic acid.
Phylogenetic trees reconstructed from the sequences suggest that EV-D68 was introduced into Stockholm several times during the outbreak. Specific association of problme parechovirus type 3 with sepsis and fever in young infants, as identified by direct typing of cerebrospinal fluid samples. None of the 2C inhibitors have progressed to in vivo studies in humans.
Intra- and interpatient evolution of enterovirus D68 analyzed by whole-genome deep sequencing
The sequencing coverage for each sample applicatuons presented in Supplementary Table S3. Thus, in this light it is not surprising that pleconaril does not possess antiviral activity against HPeV. Similar findings have been reported in three recent studies Tan et al.