Kun Li Laboratory

Research

In the past two decades, three highly pathogenic coronaviruses have emerged from animal reservoirs and caused widespread severe, and even fatal diseases in humans. SARS coronavirus (SARS-CoV) which caused severe acute respiratory syndrome (SARS) emerged in November 2002 and has disappeared by 2004. In 2012 September, another coronavirus MERS-CoV was found to be the causative agent of the Middle East respiratory syndrome (MERS) with a case fatality rate of ~33%. MERS-CoV was transmitted to humans from an animal reservoir in camels and still causes sporadic and localized outbreaks in the Middle East. The third novel coronavirus, SARS-CoV-2 emerged from China in December 2019 and causes coronavirus disease 2019 (COVID-19). It results in extremely dreadful global infection and deaths and has rapidly elevated to a global pandemic. Dr. Kun Li has been working in the virology field for more than 15 years, including 8 years in highly pathogenic human respiratory coronaviruses. He developed several mouse models of MERS-CoV and SARS-CoV-2 infection and successfully applied those mouse models to study the pathogenesis and evaluate vaccines/therapeutic candidates of MERS and COVID-19. He used the reverse genetic system to identify critical viral genes for virus replication and virulence, and 3D cell culture to study the innate immune response in airway epithelial cells as well.

His research interests include: 1) Seeking to identify the role of cystic fibrosis, asthma, and vascular permeability in COVID-19 pathogenesis and determine the mechanism of enhanced disease in patients with comorbidities. 2) Identifying critical viral genes and key host factors for SARS-CoV-2 replication and virulence. 3) Synergizing in vitro and in vivo models to develop vaccines, antibodies, small molecules, novel, and repurposed drugs for COVID-19 and other coronaviruses caused diseases.

Selected Publications

View publications for Kun Li, PhD
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1. Li K, Wohlford-Lenane C, Bartlett JA, McCray PB Jr.“Inter-individual Variation in Receptor Expression Influences MERS-CoVInfection and Immune Responses in Airway Epithelia” Frontiers in Public Health, section Infectious Diseases –Surveillance, Prevention and Treatment. 2021 (accepted)
   
   
2. Wong LR, Zheng J, Wilhelmsen K, Li K, Ortiz ME, Schnicker NJ, Pezzulo AA, Szachowicz PJ, Klumpp K, Aswad F, Rebo J, Narumiya S, Murakami M, Meyerholz DK, Fortney K, McCray PB, Perlman S. “Eicosanoid signaling as a therapeutic target in middle-aged mice with severe COVID-19” Nature 2021 (accepted)
   
   
3. Li K, Meyerholz DK, Bartlett JA, McCray PB Jr. “The TMPRSS2 Inhibitor NafamostatReduces SARS-CoV-2 Pulmonary Infection in Mouse Models of COVID-19” mBio. 2021 DOI:10.1128/mBio.00970-21
   
   
4. Li K, Wohlford-Lenane C, Bartlett JA, McCray PB Jr. “Intersubject Variation in ACE2 Protein Expression in Human Airway Epithelia and Its Relationship to Severe Acute Respiratory Syndrome Coronavirus 2” J Infect Dis. 2021 DOI:10.1093/infdis/jiab383
   
   
5. An D#, Li K#, Rowe DK#, Diaz MCH, Griffin EF, Beavis AC, Johnson SK, Padykula I, Jones CA, Briggs K, Li G, Lin Y, Huang J, Mousa J, Brindley M, Sakamoto K, Meyerholz DK, McCray PB Jr, Tompkins SM, He B. “Protection of K18-hACE2 mice and ferrets against SARS-CoV-2 challenge by a single-dose mucosal immunization with a parainfluenza virus 5–based COVID-19 vaccine” Sci Adv.2021(#Co-first author) DOI:10.1126/sciadv.abi5246
   
   
6. Sun YJ#, Velez G#, Parsons DE#, Li K#, Ortiz ME, Sharma S, McCray PB Jr, Bassuk AG, Mahajan VB. “Structure-based phylogeny identifies avoralstat as a TMPRSS2 inhibitor that prevents SARS-CoV-2 infection in mice” J Clin Invest. 2021 (#Co-first author) DOI: 10.1172/JCI147973
   
   
7. Wang ZZ#, Li K#, Maskey AR, Huang W, Toutov AA, Yang N, Srivastava K, Geliebter J, Tiwari R, Miao M, Li XM.“A small molecule compound berberineas an orally active therapeutic candidate against COVID-19 and SARS: A computational and mechanistic study” FASEB J. 2021(#Co-first author)DOI: 10.1096/fj.202001792R
   
   
8. Zheng J, Wang Y, Li K, Meyerholz DK, Allamargot C, Perlman S.“Severe Acute RespiratorySyndrome Coronavirus 2-Induced Immune Activation and Death of Monocyte-Derived Human Macrophages and Dendritic Cells” J Infect Dis. 2021DOI: 10.1093/infdis/jiaa753 
   
   
9. Zheng J#, Wong LR#, Li K#, Verma AK#, Ortiz ME, Wohlford-Lenane C, LeidingerMR, Knudson CM, Meyerholz DK, McCray PB Jr, Perlman S. “COVID-19 treatments and pathogenesis including anosmia in K18-hACE2 mice” Nature. 2021(#Co-first author).DOI:10.1038/s41586-020-2943-z
   
   
10. Gutierrez-Alvarez J, Wang L, Fernandez-Delgado R, Li K, McCrayPB Jr, Perlman S, Sola I, Zuñiga S, Enjuanes L.“Middle East Respiratory Syndrome Coronavirus Gene 5 Modulates Pathogenesis in Mice” J Virol. 2021 DOI:10.1128/JVI.01172-20
    
    
11. Wong LR, Li K, Sun J, Zhuang Z, Zhao J, McCray PB Jr, Perlman S.“Sensitization ofNon-permissive Laboratory Mice to SARS-CoV-2 with a Replication-Deficient Adenovirus Expressing Human ACE2” STAR Protoc. 2020 DOI: 10.1016/j.xpro.2020.100169
    
    
12. Sun J#, Zhuang Z#, Zheng J#, Li K#, Wong RL#, Liu D#, Huang J#, He J#, Zhu A#, Zhao J#, Li X#, Xi Y#, Chen R, Alshukairi AN, Chen Z, Zhang Z, Chen C, Huang X, Li F, Lai X, Chen D, Wen L, Zhuo J, Zhang Y, Wang Y, Huang S, Dai J, Shi Y, Zheng K, Leidinger MR, Chen J, Li Y, Zhong N, Meyerholz DK, McCray PB Jr., Perlman S, Zhao J “Generation of a broadly useful model for COVID-19 pathogenesis vaccination, and treatment”Cell. 2020(#Co-first author) DOI:10.1016/j.cell.2020.06.010
    
    
13. LiK, Li Z, Wohlford-Leane C, Meyeholz DK, Channappanavar R, An D, Perlman S, McCray PB Jr., He B. “Single-dose, intranasal immunization of recombinant parainfluenza virus 5 expressing MERS-CoV spike protein protects mice from fatal MERS-CoV infection” mBio.2020DOI:10.1128/mBio.00554-20
    
    
14. Li K, McCray PB Jr. “Chapter: Development of a mouse-adapted MERS coronavirus”Methods Mol Biol. 2020DOI:10.1007/978-1-0716-0211-9_13
    
    
15. Earnest JT, Hantak MP, Li K, McCray PB Jr, Perlman S, Gallagher T. “The tetraspaninCD9 facilitates MERS-coronavirus entry by scaffolding host cell receptors and proteases” PLoS Pathog.2017 DOI:10.1371/journal.ppat.1006546
    
    
16. Li K, Wohlford-Lenane C, Channappanavar R, Park JE, Bair TB, Flaherty H, Gallagher T, MeyerholzDK, Perlman S, McCray PB Jr. “Mouse Adapted MERS-Coronavirus Causes Lethal Lung Disease in Human DPP4 Knock-in Mice” ProC Natl Acad Sci USA. 2017 DOI:10.1073/pnas.1619109114
    
    
17. Park JE, Li K, Barlan A, Fehr AR, Perlman S, McCray PB Jr, Gallagher T. “Proteolytic Processing of Middle East respiratory syndrome coronavirus spikes expands virus tropism” Proc Natl Acad Sci USA. 2016 DOI:10.1073/pnas.1608147113
    
    
18. Li K, Wohlford-Lenane C, Perlman S, Zhao J, Jewell AK, Reznikov LR, Gibson-Corley KN, Meyerholz DK, McCray PB Jr. “Middle East Respiratory Syndrome Coronavirus Causes Multiple Organ Damage and Lethal Disease in Mice Transgenic for Human Dipeptidyl Peptidase 4”J Infect Dis. 2015 DOI:10.1093/infdis/jiv499
    
    
19. Li K,Jia R,Li M,Zheng YM,Miao C,Yao Y,Ji HL,Geng Y,Qiao W,Albritton LM,Liang C,Liu SL. “A sorting signal suppresses IFITM1 restriction of viral entry” J Biol Chem.2015 DOI:10.1074/jbc.M114.630780
    
    
20. Zhao J, Li K, Wohlford-Lenane C, Agnihothram SS, Fett C, Zhao J, Gale MJ Jr, Baric RS, EnjuanesL, Gallagher T, McCray PB Jr, Perlman S. “Rapid generation of a novel mouse model for Middle East Respiratory Syndrome” Proc Natl Acad Sci U S A. 2014 DOI:10.1073/pnas.1323279111
    
    
21. Barlan A, Zhao J, Sarkar MK, Li K, McCray PB Jr, Perlman S, Gallagher T. “Receptor variation and susceptibility to MERS coronavirus infection”J Virol. 2014 DOI:10.1128/JVI.00161-14
    
    
22. Li K#, Markosyan RM#, Zheng YM#, Golfetto O, Bungart B, Li M, Ding S, He Y, Liang C, Lee JC, Gratton E, Cohen FS, Liu SL.“IFITM proteins restrict viral membrane hemifusion” PLoS Pathog. 2013 (#Co-first author)DOI:10.1371/journal.ppat.1003124
    
    
23. Côté M, Zheng YM, Li K, Xiang SH, Albritton LM, Liu SL. “Critical role of leucine-valine change in distinct low pH requirements for membrane fusion between two related retrovirus envelopes”J Biol Chem. 2012 DOI:10.1074/jbc.M111.334722
    
    
24. Peng Y#,LiK#,Pei RJ,Wu CC,Liang CY,Wang Y,Chen XW. “The protamine likeDNA-bindingproteinP6.9epigeneticallyupregulatesAutographa californiaca multiple-nucleopolyhedrovirusgenetranscriptionin the late infection phase” Virol Sin.2012 (#Co-first author)DOI:10.1007/s12250-012-3229-x
    
    
25. Li K#, Wang Y#, Bai H, Wang Q, Song J, Zhou Y, Wu C, Chen X. “The putative pocket protein binding site of Autographa californica nucleopolyhedrovirus BV/ODV-C42 is required for virus-induced nuclear actin polymerization” J Virol. 2010 (#Co-first author) DOI:10.1128/JVI.00174-10