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Middle East respiratory syndrome coronavirus (MERS-CoV) remains a threat to public health worldwide; however, effective vaccine or drug against CoVs remains unavailable. CoV helicase is one of the three evolutionary most conserved proteins in nidoviruses, thus making it an important target for drug development. We report here the first structure of full-length coronavirus helicase, MERS-CoV nsp13. MERS-CoV helicase has multiple domains, including an N-terminal Cys/His rich domain (CH) with three zinc atoms, a beta-barrel domain and a C-terminal SF1 helicase core with two RecA-like subdomains. Our structural analyses show that while the domain organization of nsp13 is conserved throughout nidoviruses, the individual domains of nsp13 are closely related to the equivalent eukaryotic domains of Upf1 helicases. The most distinctive feature differentiating CoV helicases from eukaryotic Upf1 helicases is the interaction between CH domain and helicase core.

PurposeTo evaluate the association between the AL/CR ratio and refractive state and explore the effectiveness of this ratio in the assessment of myopia, especially when combined with uncorrected visual acuity in schoolchildren among whom myopia is common.MethodsCross sectional study. 4686 children from 6 primary schools, aged from 6 to 12 years were selected using the clustered-stratified random sampling method. Uncorrected visual acuity (UCVA), axial length (AL), corneal radius of curvature (CR), and cycloplegic refraction were tested. Refraction was measured as the spherical equivalent (SE).Results3922 children were included in the analysis. The mean AL/CR ratio was 2.973±0.002, increased with age, and different in gender. The coefficients of correlations of the SE with the AL/CR ratio, AL, and CR were -0.811, -0.657, and 0.095, respectively. Linear regression showed a 10.72 D shift towards myopia with every 1 unit increase in the AL/CR ratio (P<0.001, r2 = 66.4%). The estimated SE values obtained by substituting the AL/CR ratio and gender back to the regression model that were within a difference of ±0.50 D in ATE/LER (allowable total error and limits for erroneous results) zones compared to the actual measured values was 51%. The area under the ROC curve of the AL/CR ratio, AL, and UCVA for myopia detection were 0.910, 0.822, and 0.889, respectively, and the differences between each pair were statistically significant (P<0.01). At a specificity of 90%, the sensitivities were 72.98%, 50.50%, 71.99%, and 82.96%, respectively, for the AL/CR ratio, AL, UCVA, and the combination of the AL/CR ratio and UCVA.ConclusionsThe AL/CR ratio was found to explain the total variance in SE better than AL alone. The effectiveness of the AL/CR ratio was statistically significantly better than UCVA for detecting myopia in children, and combining the two produced increased sensitivity without significantly decreasing specificity.

The prevalence of myopia was lower or comparable to that reported in other populations from age 3 to 5 years, but increased dramatically after 6 years, consistent with a strong environmental role of schooling on myopia development.