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Search Results: 1 - 10 of 24012 matches for " Shibo Jiang "
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Respiratory Syncytial Virus Entry Inhibitors Targeting the F Protein
Zhiwu Sun,Yanbin Pan,Shibo Jiang,Lu Lu
Viruses , 2013, DOI: 10.3390/v5010211
Abstract: Human respiratory syncytial virus (RSV) is the main viral cause of respiratory tract infection in infants as well as some elderly and high-risk adults with chronic pulmonary disease and the severely immunocompromised. So far, no specific anti-RSV therapeutics or effective anti-RSV vaccines have been reported. Only one humanized monoclonal antibody, Palivizumab, has been approved for use in high-risk infants to prevent RSV infection. Ribavirin is the only drug licensed for therapy of RSV infection, but its clinical use is limited by its nonspecific anti-RSV activity, toxic effect, and relatively high cost. Therefore, development of novel effective anti-RSV therapeutics is urgently needed. The RSV envelope glycoprotein F plays an important role in RSV fusion with, and entry into, the host cell and, consequently, serves as an attractive target for developing RSV entry inhibitors. This article reviews advances made in studies of the structure and function of the F protein and the development of RSV entry inhibitors targeting it.
Study on the Systemic Risk of China’s Stock Markets under Risk-Neutral Conditions  [PDF]
Shibo Dai, Handong Li
Journal of Mathematical Finance (JMF) , 2019, DOI: 10.4236/jmf.2019.91005
Abstract: Based on stochastic discount factor theory, this paper proposes a method to convert the traditional systemic risk measures of financial markets, such as VaR, ES, MES and SES, into risk-neutral measures. We proposed a novel way to neutralize the returns without relying on option price information. Then, we empirically analyzed and compared the systemic risks and changes between the A-shares in Shanghai and H-shares in Hong Kong before and after a stock market crash, and we found that systematic risk measures under risk neutrality could more accurately determine market system risks than traditional systemic risk measures. Moreover, these systemic risk measures have a certain market risk warning effect.
Genomic Signature and Mutation Trend Analysis of Pandemic (H1N1) 2009 Influenza A Virus
Chungen Pan,Byron Cheung,Suiyi Tan,Chunling Li,Lin Li,Shuwen Liu,Shibo Jiang
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0009549
Abstract: A novel swine-origin pandemic influenza A(H1N1) virus (H1N1pdm, also referred to as S-OIV) was identified as the causative agent of the 21st century's first influenza pandemic, but molecular features conferring its ability of human-to-human transmission has not been identified. Here we compared the protein sequences of 2009 H1N1pdm strains with those causing other pandemics and the viruses isolated from humans, swines and avians, and then analyzed the mutation trend of the residues at the signature and non-signature positions, which are species- and non-species-associated, respectively, in the proteins of H1N1pdm during the pandemic of 2009. We confirmed that the host-specific genomic signatures of 2009 H1N1pdm, which are mainly swine-like, were highly identical to those of the 1918 H1N1pdm. During the short period of time when the pandemic alert level was raised from phase 4 to phase 6, one signature residue at the position of NP-100 mutated from valine to isoleucine. Four non-signature residues, at positions NA-91, NA-233, HA-206, and NS1-123, also changed during the epidemic in 2009. All these mutant residues, except that at NA-91, are located in the viral functional domains, suggesting that they may play roles in the human adaption and virulence of 2009 H1N1pdm.
HIV-1 gp41 Core with Exposed Membrane-Proximal External Region Inducing Broad HIV-1 Neutralizing Antibodies
Ji Wang,Pei Tong,Lu Lu,Leilei Zhou,Liling Xu,Shibo Jiang,Ying-hua Chen
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0018233
Abstract: The membrane-proximal external region (MPER) of the HIV-1 gp41 consists of epitopes for the broadly cross-neutralizing monoclonal antibodies 2F5 and 4E10. However, antigens containing the linear sequence of these epitopes are unable to elicit potent and broad neutralizing antibody responses in vaccinated hosts, possibly because of inappropriate conformation of these epitopes. Here we designed a recombinant antigen, designated NCM, which comprises the N- and C-terminal heptad repeats that can form a six-helix bundle (6HB) core and the MPER domain of gp41. Two mutations (T569A and I675V) previously reported to expose the neutralization epitopes were introduced into NCM to generate mutants named NCM(TA), NCM(IV), and NCM(TAIV). Our results showed that NCM and its mutants could react with antibodies specific for 6HB and MPER of gp41, suggesting that these antigens are in the form of a trimer of heterodimer (i.e., 6HB) with three exposed MPER tails. Antigen with double mutations, NCM(TAIV), elicited much stronger antibody response in rabbits than immunogens with single mutation, NCM(TA) and NCM(IV), or no mutation, NCM. The purified MPER-specific antibodies induced by NCM(TAIV) exhibited broad neutralizing activity, while the purified 6HB-specific antibodies showed no detectable neutralizing activity. Our recombinant antigen design supported by an investigation of its underlying molecular mechanisms provides a strong scientific platform for the discovery of a gp41 MPER-based AIDS vaccine.
Efficacy, Stability, and Biosafety of Sifuvirtide Gel as a Microbicide Candidate against HIV-1
Liangzhu Li, Yinyin Ben, Songhua Yuan, Shibo Jiang, Jianqing Xu, Xiaoyan Zhang
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0037381
Abstract: Sifuvirtide is a proven effective HIV-1 entry inhibitor and its safety profile has been established for systemic administration. The present study evaluated the potential of sifuvirtide formulated in a universal gel for topical use as a microbicide candidate for preventing sexual transmission of HIV. Our data showed that sifuvirtide formulated in HEC gel is effective against HIV-1 B, C subtypes, CRF07_BC and CRF01_AE, the latter two recombinants represents the most prevalent strains in China. In addition, we demonstrated that sifuvirtide in gel is stable for at least 8 weeks even at 40°C, and did not cause the disruption of integrity of mucosal epithelial surface, or the up-regulation of inflammatory cytokines both in vitro or in vivo. These results suggest that sifuvirtide gel is an effective, safe and stable product, and should be further tested as a vaginal or rectal microbicide in pre-clinical model or clinical trial for preventing HIV sexual transmission.
Measuring similarities between gene expression profiles through new data transformations
Kyungpil Kim, Shibo Zhang, Keni Jiang, Li Cai, In-Beum Lee, Lewis J Feldman, Haiyan Huang
BMC Bioinformatics , 2007, DOI: 10.1186/1471-2105-8-29
Abstract: We explored several different transformation schemes to construct the feature spaces that include a space whose features are determined by the mutual differences of the original expression components, a space derived from a parametric covariance matrix, and the principal component space in traditional PCA analysis. The former two are the newly proposed and the latter is explored for comparison purposes. The new measures we defined in these feature spaces were employed in a K-means clustering procedure to perform analyses. Applying these algorithms to a simulation dataset, a developing mouse retina SAGE dataset, a small yeast sporulation cDNA dataset, and a maize root affymetrix microarray dataset, we found from the results that the algorithm associated with the first feature space, named TransChisq, showed clear advantages over other methods.The proposed TransChisq is very promising in capturing meaningful gene expression clusters. This study also demonstrates the importance of data transformations in defining an efficient distance measure. Our method should provide new insights in analyzing gene expression data. The clustering algorithms are available upon request.With the explosion of various 'omic' data, a general question facing the biologists and statisticians is how to summarize and organize the observed data into meaningful structures. Clustering is one of the methods that have been widely explored for this purpose [1-3]. In particular, clustering is being generally applied to gene expression data to group genes with similar expression profiles into discrete functional clusters. Many clustering methods are available, including hierarchical clustering [4], K-means clustering [5], self-organizing maps [6], and various model-based methods [7-9].Recent research in clustering analysis has been focused largely on two areas: estimating the number of clusters in data [10-12] and the optimization of the clustering algorithms [13,14]. In this paper we studied a differe
Anti-HIV-1 activity of cellulose acetate phthalate: Synergy with soluble CD4 and induction of "dead-end" gp41 six-helix bundles
A Robert Neurath, Nathan Strick, Shibo Jiang, Yun-Yao Li, Asim K Debnath
BMC Infectious Diseases , 2002, DOI: 10.1186/1471-2334-2-6
Abstract: Enzyme-linked immunosorbent assays (ELISA) were used to study CAP binding to HIV-1-sCD4 complexes and to detect gp41 six-helix bundles accessible on virus particles using antibodies specific for the α-helical core domain of gp41.1) Pretreatment of HIV-1 with sCD4 augments subsequent binding of CAP; 2) there is synergism between CAP and sCD4 for inhibition of HIV-1 infection; 3) treatment of HIV-1 with CAP induced the formation of gp41 six-helix bundles.CAP and sCD4 bind to distinct sites on HIV-1 IIIB and BaL virions and their simultaneous binding has profound effects on virus structure and infectivity. The formation of gp41 six-helical bundles, induced by CAP, is known to render the virus incompetent for fusion with target cells thus preventing infection.Cellulose acetate phthalate (CAP) is a promising microbicide candidate for prevention of infection by sexually transmitted disease (STD) pathogens, including HIV-1 [1-7]. CAP inactivates HIV-1 and blocks the coreceptor binding site on the virus envelope glycoprotein gp120, while leaving the site for the primary cellular receptor CD4 accessible [8,9] Soluble CD4 (sCD4) was shown to inhibit HIV-1 infection by two mechanisms: reversible blockage of virus binding to receptors, and irreversible inactivation of virus infectivity [10]. Since CAP and sCD4 bind to distinct domains on the HIV-1 envelope, it was of interest to determine whether or not these two ligands affect virus infectivity synergistically as do other combinations of anti-HIV-1 drugs and sCD4 [11,12] Binding of sCD4 leads to conformational changes in gp120 [13-17]. Binding of gp120 to coreceptors CXCR4 and CCR5, respectively, triggers additional conformational changes in HIV-1 envelope glycoproteins [18,19] For these reasons it was of interest to determine whether a) pretreatment of HIV-1 with sCD4 would affect subsequent binding of CAP to virus particles, and b) CAP binding to virus particles in the presence or absence of sCD4 would elicit conformational
Potent and persistent antibody responses against the receptor-binding domain of SARS-CoV spike protein in recovered patients
Zhiliang Cao, Lifeng Liu, Lanying Du, Chao Zhang, Shibo Jiang, Taisheng Li, Yuxian He
Virology Journal , 2010, DOI: 10.1186/1743-422x-7-299
Abstract: Two panels of serum samples from recovered SARS patients were included and the antibody responses against the RBD were measured by ELISA and micro-neutralization assays. We found that the RBD of S protein induced potent antibody responses in the recovered SARS patients and RBD-specific antibodies could persist at high titers over three year follow-up. Furthermore, affinity purified anti-RBD antibodies possessed robust neutralizing activity.The RBD of SARS-CoV is highly immunogenic in humans and mediates protective responses and RBD-based vaccines and diagnostic approaches can be further developed.The global outbreak of severe acute respiratory syndrome (SARS), caused by a novel coronavirus (SARS-CoV), resulted in more than 8,000 cases with a fatality rate of about 10%. Impressively, the rapid spread of SARS-CoV made a great impact on public health and social-economic stability. It is thought that SARS-CoV might originate from its natural reservoir bats and transmit to humans through an intermediate such as palm civets and raccoon dogs, and no one can exclude the possibility of its recurrence [1].SARS-CoV is an enveloped positive-stranded RNA virus and its "crown"-like spike (S) protein has two major biological functions: 1) mediating receptor (angiotensin converting enzyme 2, ACE2) binding and membrane fusion; 2) inducing neutralizing antibody responses [2,3]. The S protein was considered as an important target for developing diagnostics, vaccines and therapeutics [4-12]. The receptor-binding domain (RBD) of S protein was defined as a fragment corresponding to the residues 318 - 510 of the S protein, which mediates viral binding to cell receptor ACE2 [13-15]. Coincidently, we identified the RBD as a major target of neutralizing antibodies [16-19], and proposed it as an ideal vaccine antigen for clinical application [20-22]. The immunogenicity and protective efficacy of RBD-based vaccine candidates have been evaluated in animal models [17,23-25]. However, the antigen
The interaction between the membrane-proximal external region and the N-trimer region of HIV-1 gp41: Involvement in viral fusion
Jing Li,Lu Lu,Fan Wu,Xi Chen,Ben Niu,ShiBo Jiang,YingHua Chen
Chinese Science Bulletin , 2009, DOI: 10.1007/s11434-009-0280-6
Abstract: The membrane proximal external region (MPER) of gp41 is extremely conserved among diverse HIV-1 variants, implying its important role in viral infection. Interestingly, two of the most broadly neutralizing antibodies, 2F5 and 4E10, specifically recognize this region. Our previous study demonstrated that the antigenicity and immunogenicity of 4E10 epitope are affected by remodeling gp41 fusion core, suggesting that the MPER may be associated with gp41 core and involved in gp41-mediated membrane fusion. Here we measured the binding activity of 4E10 epitope peptide (D4E10P) with various gp41 core-derived peptides and found that the N-trimer region in a construct designated N-trimer-6HB interacted significantly with D4E10P. Using N-trimer-6HB to screen a phage library, we identified a motif (WF) located in 4E10 epitope that may play a certain role in the interaction of gp41 MPER with the N-trimer in gp41 fusion core and, we thus speculated upon the potential involvement of MPER in the fusion process between viral envelope and target cell membrane.
The interaction between the membrane-proximal external region and the N-trimer region of HIV-1 gp41: Involvement in viral fusion

Jing Li,Lu Lu,Fan Wu,Xi Chen,Ben Niu,ShiBo Jiang,YingHua Chen,

科学通报(英文版) , 2009,
Abstract: The membrane proximal external region (MPER) of gp41 is extremely conserved among diverse HIV-1 variants, implying its important role in viral infection. Interestingly, two of the most broadly neutralizing antibodies, 2F5 and 4E10, specifically recognize this region. Our previous study demonstrated that the antigenicity and immunogenicity of 4E10 epitope are affected by remodeling gp41 fusion core, suggesting that the MPER may be associated with gp41 core and involved in gp41-mediated membrane fusion. Here we measured the binding activity of 4E10 epitope peptide (D4E10P) with various gp41 core-derived peptides and found that the N-trimer region in a construct designated N-trimer-6HB interacted significantly with D4E10P. Using N-trimer-6HB to screen a phage library, we identified a motif (WF) located in 4E10 epitope that may play a certain role in the interaction of gp41 MPER with the N-trimer in gp41 fusion core and, we thus speculated upon the potential involvement of MPER in the fusion process between viral envelope and target cell membrane. Supported by National Key Basic Research and Development Program of China (Grant No. 2007CB914402)
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