Dongna Zhang

Shanghai Ocean University

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Likun Xu

Institute of Microbiology

Kaichang Kou

Northwestern Polytechnical University

Zhuchun Bei

Academy of Military Medical Sciences

Yabin Song

Institute of Microbiology

Yabin Song

Institute of Microbiology

Liangliang Zhao

Institute of Microbiology

Hongquan Wang

Aerospace Center Hospital

Dake Chen

Second Institute of Oceanography

Chi Keung Marco Lau

University of Hong Kong

Min Chao

Shanghai Jiao Tong University

Cooperative Institutions

Chinese Academy of Sciences

Institute of Microbiology

Academy of Military Medical Sciences

University of Chinese Academy of Sciences

Northwestern Polytechnical University

Second Institute of Oceanography

Chinese Academy of Medical Sciences & Peking Union Medical College

Ministry of Natural Resources

Sun Yat-sen University

Shanghai Institute of Materia Medica

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Design, Synthesis, and Biological Evaluation of Benzimidazole Derivatives as Potential Lassa Virus Inhibitors

Molecules (2023)

Jinwei Chen Likun Xu Baogang Wang Dongna Zhang Liangliang Zhao

The Lassa virus (LASV) causes Lassa fever, a highly infectious and lethal agent of acute viral hemorrhagic fever. At present, there are still no effective treatments available, creating an urgent need to develop novel therapeutics. Some benzimidazole compounds targeting the arenavirus envelope glycoprotein complex (GPC) are promising inhibitors of LASV. In this study, we synthesized two series of LASV inhibitors based on the benzimidazole structure. Lentiviral pseudotypes bearing the LASV GPC were established to identify virus entry inhibitors. Surface plasmon resonance (SPR) was further used to verify the binding activities of the potential compounds. Compounds 7d-Z, 7h-Z, 13c, 13d, and 13f showed relatively excellent antiviral activities with IC50 values ranging from 7.58 to 15.46 nM and their SI values above 1251. These five representative compounds exhibited stronger binding affinity with low equilibrium dissociation constants (KD < 8.25 × 10-7 M) in SPR study. The compound 7h-Z displayed the most potent antiviral activity (IC50 = 7.58 nM) with a relatively high SI value (2496), which could be further studied as a lead compound. The structure-activity relationship indicated that the compounds with lipophilic and spatially larger substituents might possess higher antiviral activity and a much larger safety margin. This study will provide some good guidance for the development of highly active compounds with a novel skeleton against LASV.

Benzimidazole

Lassa virus

10.3390/molecules28041579

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Citations (10)

Using feedback control approach to guarantee QoS issues in mapserver

Jianbo Lǚ Haipeng Li Dongna Zhang

Currently, the Web Services has been increasing more and more popular on Internet. In recent years, the issue of quality of services (QoS) has become the major research focus, especially for the next generation of Internet frameworks. QoS problem is the delay of response time. There are two major technologies under the QoS framework, including services and differentiated services. The WebGIS Quality of Service (QoS) control should be deployed in WebGIS application servers (mapserver) in order to meet different requirements from clients and applications. In this paper, we use classical feedback control theory, i.e. the delay guarantee to contribute a QoS guarantee method to guarantee the QoS issue in mapserver. The delay guarantee includes absolutely delay guarantee and relative delay guarantee. The delay guarantee is designed to ensure that the average queuing delay for the requests with high priority is no more than the threshold configured.

Mobile QoS

Queuing delay

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Notch signaling suppresses CD14⁺ monocytes cells activity in patients with chronic hepatitis C

Apmis (2019)

Zhihong Zhang Han Wang Dongna Zhang Guangze Zhu

Hepatitis C virus (HCV) infection always leads to chronic hepatitis via dysregulation of host immunity. Notch signaling also modulates the response of monocytes/macrophages. Thus, we aimed to investigate the regulatory role of Notch signaling to CD14 + monocytes. Forty patients with chronic hepatitis C and twenty normal controls (NC) were enrolled. CD14 + monocytes and CD4 + T cells were purified from peripheral bloods. Notch receptors' mRNA expression in CD14 + monocytes was semi‐quantified by real‐time PCR. Cytokine production by CD14 + monocytes in response to γ‐secretase inhibitor (GSI) was investigated by ELISA. GSI‐induced CD14 + monocytes activity to HCV clearance in Huh7.5 cells and to CD4 + T cell differentiation was also assessed in direct and indirect contact co‐culture system. Notch1 mRNA relative level was approximately 10‐fold elevated in CD14 + monocytes from chronic hepatitis C patients when compared with NC. GSI stimulation resulted in enhanced cytokines production by CD14 + monocytes from chronic hepatitis C patients. GSI‐stimulated CD14 + monocytes from chronic hepatitis C patients induced suppression of HCV RNA replication in both direct and indirect contact co‐culture system of CD14 + monocytes and HCVcc‐infected Huh7.5 cells, and this process was accompanied by elevation of interferon‐γ production but not increased target cell death. Moreover, GSI stimulation also enhanced CD14 + monocytes‐induced Th1 and Th17 cells activation, and this process required direct cell‐to‐cell contact. Effective antiviral therapy down‐regulated Notch1 mRNA expression and promoted cytokine production by CD14 + monocytes from chronic hepatitis C. Current data revealed an important immunoregulatory property of Notch signaling to CD14 + monocytes in chronic HCV infection.

Monocyte

10.1111/apm.12980

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Citations (3)

Preparation and characterization of PTFE-g-GMA modified PTFE/SiO2 organic–inorganic hybrids

Journal of Polymer Research (2012)

Dongna Zhang Kaichang Kou Pan Gao Hou Mei Min Chao

Thermogravimetric analysis

Hybrid material

10.1007/s10965-012-9873-x

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Citations (10)

Design and Implementation of intrusion detection punctual response system

Yafang Lou Dongna Zhang Zhe Lv

With the rapid development of IT technology and Internet, Network security has become an unavoidable issue, the pure firewall strategy can't satisfy the need of safe and highly sensitive departments.The network defense must adopt a deep, various means, intrusion response technology research has become a pressing matter of the moment.The system model using ACE adaptive communication environment, using object-oriented open source (OO) framework, the fusion of multi thread, XML technology developed.it has autonomous, adaptive, real-time features.

Firewall (physics)

10.2991/icmmcce-15.2015.325

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Citations (1)

Viral polymerase inhibitors T-705 and T-1105 are potential inhibitors of Zika virus replication

Archives of Virology (2017)

Lei Cai Yajie Sun Yabin Song Likun Xu Zhuchun Bei

Since 2015, 69 countries and territories have reported evidence of vector-borne Zika virus (ZIKV) transmission. Currently, there are no effective licensed vaccines or drugs available for the treatment or prevention of ZIKV infection. We tested a series of compounds for their ability to inhibit ZIKV replication in cell culture. The compounds in T-705 (favipiravir) and T-1105 were found to have antiviral activity, suggesting that these compounds are promising candidates for further development as specific antiviral drugs against ZIKV.

Zika Virus

Favipiravir

Antiviral drug

10.1007/s00705-017-3436-8

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Citations (32)

Spray-Dried Inhalable Powder Formulations of Gentamicin Designed for Pneumonic Plague Therapy in a Mouse Model

Pharmaceutics (2022)

Menghuan Zhu Dongna Zhang Lili Zhang Liangliang Zhao Likun Xu

Infection with Yersinia pestis (Y. pestis) may cause pneumonic plague, which is inevitably fatal without treatment. Gentamicin (GM), an aminoglycoside antibiotic, is a drug commonly used in the treatment of plague. However, it requires repeated intramuscular or intravenous administration. Pulmonary drug delivery is noninvasive, with the advantages of local targeting and reduced risk of systemic toxicity. In this study, GM powders were prepared using spray-drying technology. The powders displayed good physical and chemical properties and met the requirements for human pulmonary inhalation. The formulation of the powders was optimized using a 32 full factorial design. A formulation of 15% (w/w) of L-leucine was prepared, and the spray-drying process parameters using an inlet temperature of 120°C and a 15% pump rate were determined to produce the best powder. In addition, the optimized GM spray-dried powders were characterized in terms of morphology, crystallinity, powder fluidity, and aerodynamic particle size distribution analysis. In a mouse model of pneumonic plague, we compared the therapeutic effects among three administration routes, including subcutaneous injection, liquid atomization, and dry powder atomization. In conclusion, our data suggest that inhalation therapy with GM spray-dried powders is an effective treatment for pneumonic plague.

Yersinia pestis

plague

Therapeutic effect

10.3390/pharmaceutics14122646

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Citations (2)

Testing the Club Convergence Dynamics of the COVID-19 Vaccination Rates Across the OECD Countries

Frontiers in Public Health (2022)

Weibin Xu Chi Keung Marco Lau Dongna Zhang Oladoke Oke

Vaccines are essential to create a more resilient economic growth model. Ending the COVID-19 pandemic requires a more coordinated, effective, and equitable distribution of vaccines across the countries. Therefore, governments are in a race to increase the vaccination rates of the population. Given this backdrop, this paper focuses on the daily vaccinations per million data from March 1, 2021, to October 15, 2021, in 37 Organization for Economic Co-operation and Development (OECD) countries and examines the stochastic properties of the vaccination rates. We adopt the club convergence econometric methodology to investigate the club convergence paths of COVID-19 vaccination rates in OECD regions. The results indicate a significant convergence of the vaccination rates in seven clubs across 30 OECD countries. Moreover, there are seven OECD countries demonstrate non-convergent characteristics, which raises questions about ineffective vaccine balance. In addition, the paper also discusses the potential implications for the post-COVID-19 era.

Pandemic

Convergence clubs

10.3389/fpubh.2022.872561

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Permeation Characteristic and Mechanism of CO2 in High Density Polyethylene

Lecture notes in mechanical engineering (2018)

Houbu Li Dongming Yang Dongna Zhang Zhu Yuanyuan Pengli Ge

High-density polyethylene

10.1007/978-981-13-0107-0_93

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Synthesis and in vivo antimalarial activity of novel naphthoquine derivatives with linear/cyclic structured pendants

Future Medicinal Chemistry (2017)

Tang Ling Zhuchun Bei Yabin Song Likun Xu Hong Wang

Aim: Naphthoquine (NQ) was discovered by our institute as an antimalarial candidate in 1980s, and currently employed as an artemisinin-based combination therapy partner drug. Resistance to NQ was found in mouse model in laboratory, and might emerge in future as widely used. Methodology: We herein report the design and synthesis of NQ derivatives by replacing t-butyl moiety with linear/cyclic structured pendants. All the target compounds 6a-l and intermediates 5a-h were tested for their in vivo antimalarial activity against Plasmodium berghei K173 strain in mice. Results: Compounds 6a and 6j were found to have a comparable or slightly more potent activity (the 50% effective dose [ED50], which is required to decrease parasitemia by 50%: 0.38–0.43 mg/kg) than NQ (ED50: 0.48 mg/kg). Conclusion: The newly designed compounds 6a and 6j might be promising antimalarial candidates for further research.

Plasmodium berghei

Moiety

10.4155/fmc-2017-0058

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Citations (1)