Background This study attempts to understand coronavirus disease 2019 (COVID-19) vaccine demand and hesitancy by assessing the public’s vaccination intention and willingness-to-pay (WTP). Confidence in COVID-19 vaccines produced in China and preference for domestically-made or foreign-made vaccines was also investigated. Methods A nationwide cross-sectional, self-administered online survey was conducted on 1–19 May 2020. The health belief model (HBM) was used as a theoretical framework for understanding COVID-19 vaccination intent and WTP. Results A total of 3,541 complete responses were received. The majority reported a probably yes intent (54.6%), followed by a definite yes intent (28.7%). The perception that vaccination decreases the chances of getting COVID-19 under the perceived benefit construct (OR = 3.14, 95% CI 2.05–4.83) and not being concerned about the efficacy of new COVID-19 vaccines under the perceived barriers construct (OR = 1.65, 95% CI 1.31–2.09) were found to have the highest significant odds of a definite intention to take the COVID-19 vaccine. The median (interquartile range [IQR]) of WTP for COVID-19 vaccine was CNY¥200/US$28 (IQR CNY¥100–500/USD$14–72). The highest marginal WTP for the vaccine was influenced by socio-economic factors. The majority were confident (48.7%) and completely confident (46.1%) in domestically-made COVID-19 vaccine. 64.2% reported a preference for a domestically-made over foreign-made COVID-19 vaccine. Conclusions The findings demonstrate the utility of HBM constructs in understanding COVID-19 vaccination intent and WTP. It is important to improve health promotion and reduce the barriers to COVID-19 vaccination.

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A5-3-Ketosteroid isomerase (EC 5.3.3.1) promotes an allylic rearrangement involving intramolecular proton transfer via a dienolic intermediate. This enzyme enhances the catalytic rate by a factor of 1010. Two residues, Tyr-14, the general acid that polarizes the steroid 3-carbonyl group and facilitates enolization, and Asp-38 the general base that abstracts and transfers the 4(3-proton to the 6j3-position, contribute 104.7 and 105-6 to the rate increase, respectively. A major mechanistic enigma is the huge disparity between the pK, values of the catalytic groups and their targets. Upon binding of an analog of the dienolate intermediate to isomerase, proton NMR detects a highly deshielded resonance at 18.15 ppm in proximity to aromatic protons, and with a 3-fold preference for protium over deuterium (fractionation factor, 4) = 0.34), consistent with formation of a short, strong (low-barrier) hydrogen bond to Tyr-14. The strength of this hydrogen bond is estimated to be at least 7.1 kcal/mol. This bond is relatively inaccessible to bulk solvent and is pH insensitive. Low-barrier hydrogen bonding of Tyr-14 to the

The solution secondary structure of the highly active Y55F/Y88F "Tyr-14-only" mutant of delta 5-3-ketosteroid isomerase complexed with 19-nortestosterone hemisuccinate has been shown to consist of three helices, a six-stranded mixed beta-sheet, and five turns. The steroid binds near the general acid, Tyr-14, on helix 1, near the general base, Asp-38, on the first strand of the beta-sheet, and on the hydrophobic face of the beta-sheet [Zhao, Q., Abeygunawardana, C., & Mildvan, A. S. (1997) Biochemistry 36, 3458-3472]. On this hydrophobic face, Asp-99 is the only polar residue. Free isomerase shows a deshielded exchangeable proton resonance at 13.1 ppm assigned to the N epsilon H of neutral His-100. Its fractionation factor (phi = 0.79) and slow exchange with solvent suggest it to be buried or involved in an H-bond. The binding of dihydroequilenin or estradiol to isomerase induces the appearance of two additional deshielded proton resonances, one at 18.2 ppm assigned to the gamma-carboxyl proton of Asp-99, and the other, at 11.6 ppm, assigned to the zeta-OH proton of Tyr-14. While mutation of Asp-99 to Ala results in the disappearance of only the resonance near 18 ppm [Wu, R. W., Ebrahemian, S., Zwrotny, M. E., Thornberg, L. D., Perez-Alverado, G. C., Brothers, P., Pollack, R. M., & Summers, M. F. (1997) Science 276, 415-418], both of these resonances disappear in mutants lacking Tyr-14, suggesting an H-bonded catalytic diad, Asp-99-COOH--Tyr14-OH--O-steroid enolate. The catalytic diad is further supported by NOEs from the beta 1 and beta 2 protons of Asp-99 to the epsilon protons of Tyr-14, and from the zeta-OH proton of Tyr-14 to the gamma-carboxyl proton of Asp-99, indicating close proximity of these two residues, and by other data from the literature. A strong, low-barrier H-bond between Asp-99 and Tyr-14 is indicated by the 6.2 ppm deshielding, low fractionation factor (phi = 0.34) and slow exchange of the resonance at 18.2 ppm. A normal H-bond between Tyr-14 and the steroid is indicated by the 1.8 ppm deshielding, fractionation factor of 0.97 and the slow exchange of the resonance at 11.6 ppm. It is suggested that the 10(4.7)-fold contribution of Tyr-14 to catalysis is made possible by strong H-bonding from Asp-99 in the catalytic diad which strengthens general acid catalysis by Tyr-14. It is also noted that highly deshielded proton resonance on enzymes between 15 and 20 ppm, assigned to low-barrier H-bonds, generally involve carboxyl groups.