RESUMEN
High-fidelity replication of the large RNA genome of coronaviruses (CoVs) is mediated by a 3'-to-5' exoribonuclease (ExoN) in non-structural protein 14 (nsp14), which excises nucleotides including antiviral drugs mis-incorporated by the low-fidelity viral RNA-dependent RNA polymerase (RdRp) and has also been implicated in viral RNA recombination and resistance to innate immunity. Here we determined a 1.6-[A] resolution crystal structure of SARS-CoV-2 ExoN in complex with its essential co-factor, nsp10. The structure shows a highly basic and concave surface flanking the active site, comprising several Lys residues of nsp14 and the N-terminal amino group of nsp10. Modeling suggests that this basic patch binds to the template strand of double-stranded RNA substrates to position the 3' end of the nascent strand in the ExoN active site, which is corroborated by mutational and computational analyses. Molecular dynamics simulations further show remarkable flexibility of multi-domain nsp14 and suggest that nsp10 stabilizes ExoN for substrate RNA-binding to support its exoribonuclease activity. Our high-resolution structure of the SARS-CoV-2 ExoN-nsp10 complex serves as a platform for future development of anti-coronaviral drugs or strategies to attenuate the viral virulence.
RESUMEN
BACKGROUND: The motor neuromuscular control of the ankle is decreased in individuals with chronic ankle instability, which impairs athletic performance. Kinesio taping has been widely used in the prevention and treatment of chronic ankle instability. However, there is limited research exploring the effects of kinesio taping on motor neuromuscular control in individuals with chronic ankle instability currently, and moreover, the results are in controversy with large heterogeneity. OBJECTIVE: To describe the current research situation of the effects of kinesio taping on motor neuromuscular control in individuals with chronic ankle instability, thereby providing reliable reference in clinical practice METHODS: The first author searched the articles addressing the application of kinesio taping in chronic ankle instability from January 2009 to July 2019 in the databases of PubMed, Cochrane, WOS and CNKI. The keywords were “chronic ankle instability, ankle instability, ankle”, “kinesio tap*, kinesiology tap*, kinaesthetic tap*, tap*” in Chinese and English. RESULTS AND CONCLUSION: Kinesio taping may improve ankle proprioception and jumping biomechanical performance in individuals with chronic ankle instability, but more high-quality researches are required. There is insufficient evidence to encourage that the use of kinesio taping can facilitate muscle strength, activation characteristics and balance function in individuals with chronic ankle instability. The existing studies have extensive heterogeneity in the selection of subjects, so it is difficult to comprehensively summarize the patients with chronic ankle instability of different exercise types and levels. The included scales of different studies are different, there are obvious differences in the methods, pull, direction, and duration when using kinesio taping, and there is no uniform standard. There is a lack of high-quality meta-analysis for evidence-based argumentation.
