| 1 | Structure-activity relationship optimization for lassa virus fusion inhibitors targeting the transmembrane domain of GP2显示文摘Dear Editor,Lassa virus(LASV)belongs to the Mammarenavirus genus,Arenaviridae family.Arenaviruses are classified into two main groups-Old World(OW)and New World(NW)-based on virus genetics,serology,antigenic properties and geographical relationships.The OW LASV and Lujo virus(LUJV),as well as NW Jurn'n virus(JUNV),Machupo virus(MACV),Guanarito virus(GTOV),Sabia virus(SABV)and Chapare virus(CHAPV),are known to cause severe hemorrhagic fever and are listed as biosafety level 4(BSL-4)agents.The arenavirus glycoprotein complex(GPC)contains three subunits-the retained stable-signal peptide(SSP),the receptor-binding subunit GP1,and the membrane fusion subunit GP2(Lenz et al.,2001).Notably,the proximate external membrane region and TM of GP2,together with the ectodomain loop and TMs of SSP,form an SSP-GP2 interface,playing essential roles in regulating membrane fusion,and providing targets for distinct fusion inhibitors(Larson et al.,2008;Lee et al.,2008;York et al.,2008;York and Nunberg,2009;Thomas et al.,2011;Burgeson et al.,2013a;Shankar et al.,2016;Wang et al.,2016;Wang et al.,2018).Among these inhibitors,ST-161 is LASV specific(Burgeson et al.,2013a).In this study,we conducted structure-activity relationship(SAR)optimization of ST-161.As a result,21 derivatives with IC50 values<1 pmol/L are presented in Table S1.Hit compounds 21,29 and 57 exhibiting robust inhibition of the LASV pseudotype virus(LASVpv,VSV backbone enveloped by LASV GPC with single cycle infection)entry with IC50 values lower than 0.2 nmol/L(Figs.1A and S1),as well as hit compound 72 with an ester bond instead of acylhydrazone,were further investigated.To test whether the four hit compounds inhibit LASV entry by blocking the GPC-mediated membrane fusion,the inhibition effects of these compounds against LASV GPC mediated fusion were quantitatively determined by dual-luciferase assay(Thomas et al.,2011;Wang et al.,2018). | Guangshun Zhang Junyuan Cao Yan Cai Yang Liu Yanli Li Peilin Wang Xiaoying Jia Mengmeng Zhang Gengfu Xiao Yu Guo Wei Wang | 2019 | Protein & Cell2019，10，2： | 3 |
| 2 | Isotopic characteristics of groundwater in Changzhou, Wuxi and Suzhou area and their implications显示文摘Based on the study of groundwater isotope(2H and 18O, 34S, 15N, 3H, 14C) in Changzhou, Wuxi and Suzhou area, it is found that the deep confined groundwater has no pollution on the whole, whereas the shallow groundwater is polluted to a different degree in the area. The deep confined aquifers (main exploitation aquifers) in Changzhou area and in Wuxi and Suzhou area likely belong to two different aquifers. The main exploitation aquifers in Changzhou area are not connected with those in Wuxi and Suzhou area, or they are connected but not expedited. The lateral run-off of groundwater is at present directed to the exploitation center because of overexploitation of the deep groundwater for a long time, but the flowing speed of groundwater is still extremely slow. The deep confined groundwater is in a close to half close state. The 14C age of groundwater varies from 10000 a BP to 38000 a BP, with the oldest groundwater found at the nearest exploitation center (along the line of three cities of Changzhou, Wuxi and Suzhou) and the youngest at the furthest exploitation center. | JIANG YueHua JIA JunYuan XU NaiZhen WANG JingDong KANG XiaoJun | 2008 | Science China Earth Sciences2008，51，6： | 1 |
| 3 | Optimal control and cost-effective analysis of an agestructured emerging infectious disease model显示文摘Emerging infectious diseases are one of the global public health problems which may lead to widespread epidemics and potentially life-threatening infection.Integrated vaccination and physical distancing interventions are two elementary methods for preventing infectious diseases transmission.In this paper,we construct a continuous age-structured model for investigating the transmission dynamics of an emerging infection disease during a short period.We derive the basic regeneration number R 0,the spectral radius of the next generation operator K,which determines the disease outbreak or not.Furthermore,we propose an optimal control problem to take account for the cost-effectiveness of social distancing intervention and vaccination.We rigorously obtain sufficient conditions for a L1 control problem.Numerical simulations show that coupling integrated vaccination and physical distancing intervention could effectively eliminate the infection,and such control strategy is more sensitive for people aged 10e39 and over 60. | Peiqi Jia Junyuan Yang Xuezhi Li | 2022 | Infectious Disease Modelling2022，7，1： | 0 |
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