Chinese Center for Disease Control and Prevention

About: Chinese Center for Disease Control and Prevention is a government organization based out in Beijing, China. It is known for research contribution in the topics: Population & Acquired immunodeficiency syndrome (AIDS). The organization has 16037 authors who have published 15098 publications receiving 423452 citations. The organization is also known as: China CDC & CCDC.

Structure of Main Protease from Human Coronavirus NL63: Insights for Wide Spectrum Anti-Coronavirus Drug Design.

Abstract: First identified in The Netherlands in 2004, human coronavirus NL63 (HCoV-NL63) was found to cause worldwide infections. Patients infected by HCoV-NL63 are typically young children with upper and lower respiratory tract infection, presenting with symptoms including croup, bronchiolitis, and pneumonia. Unfortunately, there are currently no effective antiviral therapy to contain HCoV-NL63 infection. CoV genomes encode an integral viral component, main protease (M(pro)), which is essential for viral replication through proteolytic processing of RNA replicase machinery. Due to the sequence and structural conservation among all CoVs, M(pro) has been recognized as an attractive molecular target for rational anti-CoV drug design. Here we present the crystal structure of HCoV-NL63 M(pro) in complex with a Michael acceptor inhibitor N3. Structural analysis, consistent with biochemical inhibition results, reveals the molecular mechanism of enzyme inhibition at the highly conservative substrate-recognition pocket. We show such molecular target remains unchanged across 30 clinical isolates of HCoV-NL63 strains. Through comparative study with M(pro)s from other human CoVs (including the deadly SARS-CoV and MERS-CoV) and their related zoonotic CoVs, our structure of HCoV-NL63 M(pro) provides critical insight into rational development of wide spectrum antiviral therapeutics to treat infections caused by human CoVs.

Structure of the Fusion Core and Inhibition of Fusion by a Heptad Repeat Peptide Derived from the S Protein of Middle East Respiratory Syndrome Coronavirus

Abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) recently emerged as a severe worldwide public health concern. The virus is highly pathogenic, manifesting in infected patients with an approximately 50% fatality rate. It is known that the surface spike (S) proteins of coronaviruses mediate receptor recognition and membrane fusion, thereby playing an indispensable role in initiating infection. In this process, heptad repeats 1 and 2 (HR1 and HR2) of the S protein assemble into a complex called the fusion core, which represents a key membrane fusion architecture. To date, however, the MERS-CoV fusion core remains uncharacterized. In this study, we performed a series of biochemical and biophysical analyses characterizing the HR1/HR2 complexes of this novel virus. The HR sequences were variably truncated and then connected with a flexible amino acid linker. In each case, the recombinant protein automatically assembled into a trimer in solution, displaying a typical α-helical structure. One of these trimers was successfully crystallized, and its structure was solved at a resolution of 1.9 A. A canonical 6-helix bundle, like those reported for other coronaviruses, was revealed, with three HR1 helices forming the central coiled-coil core and three HR2 chains surrounding the core in the HR1 side grooves. This demonstrates that MERS-CoV utilizes a mechanism similar to those of other class I enveloped viruses for membrane fusion. With this notion, we further identified an HR2-based peptide that could potently inhibit MERS-CoV fusion and entry by using a pseudotyped-virus system. These results lay the groundwork for future inhibitory peptidic drug design.

Cardiovascular mortality risk attributable to ambient temperature in China

Abstract: Objective To examine cardiovascular disease (CVD) mortality burden attributable to ambient temperature; to estimate effect modification of this burden by gender, age and education level. Methods We obtained daily data on temperature and CVD mortality from 15 Chinese megacities during 2007–2013, including 1 936 116 CVD deaths. A quasi-Poisson regression combined with a distributed lag non-linear model was used to estimate the temperature-mortality association for each city. Then, a multivariate meta-analysis was used to derive the overall effect estimates of temperature at the national level. Attributable fraction of deaths were calculated for cold and heat (ie, temperature below and above minimum-mortality temperatures, MMTs), respectively. The MMT was defined as the specific temperature associated to the lowest mortality risk. Results The MMT varied from the 70th percentile to the 99th percentile of temperature in 15 cities, centring at 78 at the national level. In total, 17.1% (95% empirical CI 14.4% to 19.1%) of CVD mortality (330 352 deaths) was attributable to ambient temperature, with substantial differences among cities, from 10.1% in Shanghai to 23.7% in Guangzhou. Most of the attributable deaths were due to cold, with a fraction of 15.8% (13.1% to 17.9%) corresponding to 305 902 deaths, compared with 1.3% (1.0% to 1.6%) and 24 450 deaths for heat. Conclusions This study emphasises how cold weather is responsible for most part of the temperature-related CVD death burden. Our results may have important implications for the development of policies to reduce CVD mortality from extreme temperatures.

Effectiveness of first eight methadone maintenance treatment clinics in China

Abstract: Objective: To evaluate the effectiveness of the first phase of eight methadone maintenance treatment (MMT) clinics in China. Design: Repeated cross-sectional surveys. Methods: Three surveys of clients attending the first phase of eight MMT clinics were carried out at entry, and 6 and 12 months after enrolment. Drug using behaviours, drugrelated criminal activity, and relationships with families were compared for the three periods. Blood specimen were collected and tested for HIV for each client at entry, and HIV-negative clients were re-tested after 12 months. Results: A total of 585, 609 and 468 clients participated in the first, second and third surveys,respectively. The proportion of clients who injecteddrugs reduced from 69.1to 8.9 and 8.8%, and the frequency of injection in the past month had reduced from 90 times per month to twice per month, employment increased from 22.9 to 43.2 and 40.6%, and self-reported criminal behaviours reduced from 20.7 to 3.6 and 3.8% in the three surveys. By the third survey, 65.8% of clients reported a harmonious relationship with families, an increase from 46.8% at entry, and 95.9% of clients were satisfied with MMT services. Eight HIV seroconversions were found among 1153 clients during 12 months. Conclusion: The study demonstrated that the first phase MMT contributed to a reduction in drug use, drug injecting behaviours, drug-related criminal behaviours, HIV infections, and improved relationships within families among heroin users who participated in the MMT programme. MMT needs to be scaled up nationwide rapidly with improved services. 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins