Molecular Virology, Structural Biology
Lou’s research is focused on the molecular mechanism of entry, replication and pathogenesis of emerging and re-emerging high pathogenic viruses, as well as highly active antivirals development, through the combination of biophysical, virologic and chemical-biological technics.In the recent global pandemic of COVID-19, he determined the structures of the key target for antiviral development, RNA-dependent RNA polymerase, accelerating the global efforts against COVID-19 (Science, 2020).He also determined the structure and the function of the N-terminal domain of influenza virus polymerase PA subunit (Nature, 2009), determined the first complete structure of large polymerase protein encoded by negative-sense RNA virus (Nature Microbiology, 2020), discovered biological features of nucleoprotein encoded by representative bunyaviruses (including Crimean-Congo hemorrhagic fever virus, Bunyamwera virus, severe fever with thrombocytopenia syndrome virus, Hantavirus and tomato spotted wilt virus) (PNAS, 2012; PNAS, 2013; Protein Cell, 2013; JVI, 2015; JVI, 2017).To understand the receptor-virus recognition, he dissected the mechanism receptor recognition of adeno-associated virus (Nature Microbiology, 2018; Nature Communications, 2019) and picornavirus (PNAS, 2018), identified a new receptor for enterovirus-71 (PLoS Pathogens, 2014) and discovered a new receptor-ligand recognition mode (Nature, 2016). Amongst those, he also studied the molecular mechanism of dynamin-like proteins function in multiple key cellular processes (Nat Struct Mol Biol., 2018; J Cell Biol., 2015 and 2016).To date, he has published over 120 research papers, including in Nature, Science, Nature Microbiology, Nature Communications, PNAS, PLoS Pathogens and etc with more than 5,700 citations. His H-index is 40 and he also has 14 patents.
1.Structure of the RNA-dependent RNA polymerase from COVID-19 virus. Gao Y, Yan L, Huang Y, Liu F, Zhao Y, Cao L, Wang T, Sun Q, Ming Z, Zhang L, Ge J, Zheng L, Zhang Y, Wang H, Zhu Y, Zhu C, Hu T, Hua T, Zhang B, Yang X, Li J, Yang H, Liu Z, Xu W, Guddat LW, Wang Q*,Lou Z*, Rao Z*.Science. 2020 Apr 10. pii: eabb7498. doi: 10.1126/science.abb7498.
2.DWARF14 is a non-canonical hormone receptor for strigolactone. Yao R, Ming Z, Yan L, Li S, Wang F, Ma S, Yu C, Yang M, Chen L, Chen L, Li Y, Yan C, Miao D, Sun Z, Yan J, Sun Y, Wang L, Chu J, Fan S, He W, Deng H, Nan F, Li J, Rao Z*,Lou Z*, Xie D*.Nature. 2016 Aug 1. doi: 10.1038/nature19073.
3.Structure of severe fever with thrombocytopenia syndrome virus L protein elucidates the mechanisms of viral transcription initiation. Wang P, Liu L, Liu A, Yan L, He Y, Shen S, Hu M, Guo Y, Liu H, Liu C, Lu Y, Wang P, Deng F*, Rao Z*,Lou Z*.Nature Microbiology. 2020 Apr 24.
4.Divergent engagements between adeno-associated viruses with their cellular receptor AAVR. Zhang R, Xu G, Cao L, Sun Z, He Y, Cui M, Sun Y, Li S, Li H, Qin L, Hu M, Yuan Z, Rao Z, Ding W, Rao Z*,Lou Z*.Nat Commun.2019 Aug 21;10(1):3760. doi: 10.1038/s41467-019-11668-x.
5.Adeno-associated virus 2 bound to its cellular receptor AAVR. Zhang R, Cao L, Cui M, Sun Z, Hu M, Zhang R, Stuart W, Zhao X, Yang Z, Li X, Sun Y, Li S, Ding W*,Lou Z*, Rao Z.Nat Microbiol.2019 Apr;4(4):675-682. doi: 10.1038/s41564-018-0356-7. Epub 2019 Feb 11.
6.Bunyamwera virus possesses a distinct nucleocapsid protein to facilitate genome encapsidation. Li B., Wang Q., Pan X., Fernández de Castro, I., Sun Y., Guo Y., Tao X., Risco C., Sui S.F. andLou Z.*Proc Natl Acad Sci USA2013 May 28;110(22):9048-53
7.Crimean-Congo hemorrhagic fever virus nucleoprotein reveals an endonuclease activity in the Bunyaviruses. Guo Y., Wang W., Ji W., Deng M., Sun Y., Zhou H., Yang C., Deng F., Wang H., Hu Z.*,Lou Z.*and Rao Z*.Proc Natl Acad Sci USA2012 Mar 27;109(13):5046-51.
8.Cyclophilin A associates with enterovirus-71 virus capsid and plays an essential role in viral infection as an uncoating regulator. Qing J, Wang Y, Sun Y, Huang J, Yan W, Wang J, Su D, Ni C, Li J, Rao Z, Liu L*,Lou Z*.PLoS Pathog.2014 Oct 2;10(10):e1004422.
9.Structural basis for GTP hydrolysis and conformational change of MFN1 in mediating membrane fusion. Yan L, Qi Y, Huang X, Yu C, Lan L, Guo X, Rao Z, Hu J*,Lou Z*.Nat Struct Mol Biol.2018 Mar;25(3):233-243. doi: 10.1038/s41594-018-0034-8. Epub 2018 Feb 26.
10.Structures of human mitofusin 1 provide insight into mitochondrial tethering Qi Y., Yan L., Yu C., Guo X., Zhou X., Hu X., Huang X., Rao Z.,Lou Z.*, Hu J*.J Cell Biol.2016 Nov 14
11.Structures of the yeast dynamin-like GTPase Sey1p provide insight into homotypic ER fusion. Yan L, Sun S, Wang W, Shi J, Hu X, Wang S, Su D, Rao Z, Hu J*,Lou Z.*J Cell Biol.2015 Sep 14;210(6):961-72.
12.Crystal structure of an avian influenza polymerase PA(N) reveals an endonuclease active site. Yuan P.$, Bartlam M.$,Lou Z.$, Chen S., Zhou J., He X., Lv Z., Ge R., Li X., Deng T., Fodor E., Rao Z. and Liu Y.Nature.2009 Apr 16; 458(7240):909-13.(共同第一作者)
13.Formation and working mechanism of the picornavirus VPg uridylylation complex. Sun Y, Guo Y,Lou Z*.Curr Opin Virol.2014 Dec;9:24-30. doi: 10.1016/j.coviro.2014.09.003. (invited review)
14.Current progress in antiviral strategies.Lou Z*, Sun Y, Rao Z*.Trends Pharmacol Sci.2014 Feb;35(2):86-102. (invited review)
15.Structural perspective on the formation of ribonucleoprotein complex in negative-sense single-stranded RNA viruses. Zhou H, Sun Y, Guo Y,Lou Z*.Trends Microbiol.2013 Sep;21(9):475-84. (invited review)
