Research Interests

● Molecular virology of human highly pathogenic coronaviruses (SARS-CoV-2 and MERS-CoV)

● Synthetic defective influenza virus and its potential use as intradermal influenza vaccine

● Synthetic defective SARS-CoV-2 virus and its potential use as nasal COVID-19 vaccine

● Molecular mechanism of Innate Immunity

● Interferon signaling and Interferon-stimulated genes

● Single-cell RNA sequencing and immune responses

Selected Publications

Lam JY, Ng YY, Yuen CK, Wong WM, Yuen KY, Kok KH (2022) A nasal omicron vaccine booster elicits potent neutralizing antibody response against emerging SARS-CoV-2 variants. Emerg Microbes Infect. (Accepted)

Kok KH, Wong SC, Chan WM, Wen L, Chu AW, Ip JD, Lee LK, Wong IT, Lo HW, Cheng VC, Ho AY, Lam BH, Tse H, Lung D, Ng KNH, Au AK, Siu GK, Yuen KY. (2022) Co-circulation of two SARS-CoV-2 variant strains within imported pet hamsters in Hong Kong. Emerg Microbes Infect. 11:689-698.

Chan JF, Poon VK, Chan CC, Chik KK, Tsang JO, Zou Z, Chan CC, Lee AC, Li C, Liang R, Cao J, Tang K, Yuen TT, Hu B, Huang X, Chai Y, Shuai H, Luo C, Cai JP, Chan KH, Sridhar S, Yin F, Kok KH, Chu H, Zhang AJ, Yuan S, Yuen KY. (2021) Low Environmental Temperature Exacerbates Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Golden Syrian Hamsters. Clin Infect Dis. ciab817.

Li C, Chen Y, Zhao Y, Lung DC, Ye Z, Song W, Liu FF, Cai JP, Wong WM, Yip CC, Chan JF, To KK, Sridhar S, Hung IF, Chu H, Kok KH, Jin DY, Zhang AJ, Yuen KY. (2021) Intravenous injection of COVID-19 mRNA vaccine can induce acute myopericarditis in mouse model. Clin Infect Dis. ciab707.

Chu H, Shuai H, Hou Y, Zhang X, Wen L, Huang X, Hu B, Yang D, Wang Y, Yoon C, Wong BH, Li C, Zhao X, Poon VK, Cai JP, Wong KK, Yeung ML, Zhou J, Au-Yeung RK, Yuan S, Jin DY, Kok KH, Perlman S, Chan JF, Yuen KY. (2021) Targeting highly pathogenic coronavirus-induced apoptosis reduces viral pathogenesis and disease severity. Sci Adv. 7: eabf8577.

Wang X, Lam JY, Chen L, Au SW, To KKW, Yuen KY, Kok KH. (2021) Mining of linear B cell epitopes of SARS-CoV-2 ORF8 protein from COVID-19 patients. Emerg Microbes Infect. 10:1016-1023.

Wang X, Lin X, Zheng Z, Lu B, Wang J, Tan AH, Zhao M, Loh JT, Ng SW, Chen Q, Xiao F, Huang E, Ko KH, Huang Z, Li J, Kok KH, Lu G, Liu X, Lam KP, Liu W, Zhang Y, Yuen KY, Mak TW, Lu L. (2021) Host-derived lipids orchestrate pulmonary γδ T cell response to provide early protection against influenza virus infection. Nat Commun. 12:1914.

Yuan S, Yin X, Meng X, Chan JF, Ye ZW, Riva L, Pache L, Chan CC, Lai PM, Chan CC, Poon VK, Lee AC, Matsunaga N, Pu Y, Yuen CK, Cao J, Liang R, Tang K, Sheng L, Du Y, Xu W, Lau CY, Sit KY, Au WK, Wang R, Zhang YY, Tang YD, Clausen TM, Pihl J, Oh J, Sze KH, Zhang AJ, Chu H, Kok KH, Wang D, Cai XH, Esko JD, Hung IF, Li RA, Chen H, Sun H, Jin DY, Sun R, Chanda SK, Yuen KY. (2021) Clofazimine broadly inhibits coronaviruses including SARS-CoV-2. Nature. 593:418-423.

Tse H, Lung DC, Wong SC, Ip KF, Wu TC, To KK, Kok KH, Yuen KY, Choi GK. (2021) Emergence of a Severe Acute Respiratory Syndrome Coronavirus 2 Virus Variant With Novel Genomic Architecture in Hong Kong. Clin Infect Dis. 73:1696-1699.

Lau SKP, Fan RYY, Zhu L, Li KSM, Wong ACP, Luk HKH, Wong EYM, Lam CSF, Lo GCS, Fung J, He Z, Fok FCH, Au-Yeung RKH, Zhang L, Kok KH, Yuen KY, Woo PCY. (2021) Isolation of MERS-related coronavirus from lesser bamboo bats that uses DPP4 and infects human-DPP4-transgenic mice. Nat Commun. 12:216.

Chu H, Hu B, Huang X, Chai Y, Zhou D, Wang Y, Shuai H, Yang D, Hou Y, Zhang X, Yuen TT, Cai JP, Zhang AJ, Zhou J, Yuan S, To KK, Chan IH, Sit KY, Foo DC, Wong IY, Ng AT, Cheung TT, Law SY, Au WK, Brindley MA, Chen Z, Kok KH, Chan JF, Yuen KY. (2021) Host and viral determinants for efficient SARS-CoV-2 infection of the human lung. Nat Commun. 12:134.

Lu L, Fong CH, Zhang AJ, Wu WL, Li IC, Lee AC, Dissanayake TK, Chen L, Hung IF, Chan KH, Chu H, Kok KH, Yuen KY, To KK. (2022) Repurposing of Miltefosine as an Adjuvant for Influenza Vaccine. Vaccines (Basel). 8:754.

To KK, Cheng VC, Cai JP, Chan KH, Chen LL, Wong LH, Choi CY, Fong CH, Ng AC, Lu L, Luo CT, Situ J, Chung TW, Wong SC, Kwan GS, Sridhar S, Chan JF, Fan CY, Chuang VWM, Kok KH, Hung IF, Yuen KY. (2020) Seroprevalence of SARS-CoV-2 in Hong Kong and in residents evacuated from Hubei province, China: a multicohort study. Lancet Microbe. 1:e111-e118.

Lam JY, Yuen CK, Ip JD, Wong WM, To KK, Yuen KY, Kok KH. (2020) Loss of orf3b in the circulating SARS-CoV-2 strains. Emerg Microbes Infect. 9:2685-2696.

Ip JD, Kok KH, Chan WM, Chu AW, Wu WL, Yip CC, To WK, Tsang OT, Leung WS, Chik TS, Chan KH, Hung IF, Yuen KY, To KK. (2020) Intra-host non-synonymous diversity at a neutralizing antibody epitope of SARS-CoV-2 spike protein N-terminal domain. Clin Microbiol Infect. 27:1350.e1-1350.e5.

Wang X, Lam JY, Wong WM, Yuen CK, Cai JP, Au SW, Chan JF, To KKW, Kok* KH, Yuen KY. (2020) Accurate Diagnosis of COVID-19 by a Novel Immunogenic Secreted SARS-CoV-2 orf8 Protein. mBio. 11:e02431-20. (*: co-corresponding author)

Yuen CK, Wong WM, Mak LF, Wang X, Chu H, Yuen KY, Kok KH. (2021) Suppression of SARS-CoV-2 infection in ex-vivo human lung tissues by targeting class III phosphoinositide 3-kinase. J Med Virol. 93:2076-2083.

To KK, Hung IF, Chan KH, Yuan S, To WK, Tsang DN, Cheng VC, Chen Z, Kok KH, Yuen KY. (2021) Serum Antibody Profile of a Patient With Coronavirus Disease 2019 Reinfection. Clin Infect Dis. 72:e659-e662.

To KK, Hung IF, Ip JD, Chu AW, Chan WM, Tam AR, Fong CH, Yuan S, Tsoi HW, Ng AC, Lee LL, Wan P, Tso EY, To WK, Tsang DN, Chan KH, Huang JD, Kok KH, Cheng VC, Yuen KY. (2021) Coronavirus Disease 2019 (COVID-19) Re-infection by a Phylogenetically Distinct Severe Acute Respiratory Syndrome Coronavirus 2 Strain Confirmed by Whole Genome Sequencing. Clin Infect Dis. 73:e2946-e2951.

Chu H, Chan JF, Yuen TT, Shuai H, Yuan S, Wang Y, Hu B, Yip CC, Tsang JO, Huang X, Chai Y, Yang D, Hou Y, Chik KK, Zhang X, Fung AY, Tsoi HW, Cai JP, Chan WM, Ip JD, Chu AW, Zhou J, Lung DC, Kok KH, To KK, Tsang OT, Chan KH, Yuen KY. (2020) Comparative tropism, replication kinetics, and cell damage profiling of SARS-CoV-2 and SARS-CoV with implications for clinical manifestations, transmissibility, and laboratory studies of COVID-19: an observational study. Lancet Microbe. 1:e14-e23.

Yuen CK, Lam JY, Wong WM, Mak LF, Wang X, Chu H, Cai JP, Jin DY, To KK, Chan JF, Yuen KY, Kok KH. (2020) SARS-CoV-2 nsp13, nsp14, nsp15 and orf6 function as potent interferon antagonists. Emerg Microbes Infect. 9:1418-1428.

Chan WM, Ip JD, Chu AW, Yip CC, Lo LS, Chan KH, Ng AC, Poon RW, To WK, Tsang OT, Leung WS, Kwan MY, Chua GT, Chung TW, Hung IF, Kok KH, Cheng VC, Chan JF, Yuen KY, To KK. (2020) Identification of nsp1 gene as the target of SARS-CoV-2 real-time RT-PCR using nanopore whole-genome sequencing. J Med Virol. 92:2725-2734.

Chu H, Yuen TTT, Chik KKH, Yuan S, Shuai H, Zou Z, Wang Y, Zhu Z, Yang D, Poon VKM, Chan CCS, Zhou J, Yin F, Kok KH, Yuen KY, Chan JFW. (2020) Targeting the Inositol-Requiring Enzyme-1 Pathway Efficiently Reverts Zika Virus-Induced Neurogenesis and Spermatogenesis Marker Perturbations. ACS Infect Dis. 6:1745-1758.

Chu H, Chan JF, Wang Y, Yuen TT, Chai Y, Hou Y, Shuai H, Yang D, Hu B, Huang X, Zhang X, Cai JP, Zhou J, Yuan S, Kok KH, To KK, Chan IH, Zhang AJ, Sit KY, Au WK, Yuen KY. (2020) Comparative Replication and Immune Activation Profiles of SARS-CoV-2 and SARS-CoV in Human Lungs: An Ex Vivo Study With Implications for the Pathogenesis of COVID-19. Clin Infect Dis. 71:1400-1409.

Chan JF, Zhang AJ, Yuan S, Poon VK, Chan CC, Lee AC, Chan WM, Fan Z, Tsoi HW, Wen L, Liang R, Cao J, Chen Y, Tang K, Luo C, Cai JP, Kok KH, Chu H, Chan KH, Sridhar S, Chen Z, Chen H, To KK, Yuen KY. (2020) Simulation of the Clinical and Pathological Manifestations of Coronavirus Disease 2019 (COVID-19) in a Golden Syrian Hamster Model: Implications for Disease Pathogenesis and Transmissibility. Clin Infect Dis. 71:2428-2446.

Yip CC, Chan WM, Ip JD, Seng CW, Leung KH, Poon RW, Ng AC, Wu WL, Zhao H, Chan KH, Siu GK, Ng TT, Cheng VC, Kok KH, Yuen KY, To KK. (2020) Nanopore Sequencing Reveals Novel Targets for Detection and Surveillance of Human and Avian Influenza A Viruses. J Clin Microbiol. 58:e02127-19.

Chan JF, Yuan S, Kok* KH, To KK, Chu H, Yang J, Xing F, Liu J, Yip CC, Poon RW, Tsoi HW, Lo SK, Chan KH, Poon VK, Chan WM, Ip JD, Cai JP, Cheng VC, Chen H, Hui CK, Yuen KY. (2020) A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet. 395:514-523. (*: co-first author) (IF: 59.102)

Chan JF, Kok* KH, Zhu Z, Chu H, To KK, Yuan S, Yuen KY. (2020) Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg Microbes Infect. 9:221-236. (*: co-first and co-corresponding author) (IF: 6.212)

Lee AC, Zhang AJ, Chu H, Li C, Zhu H, Mak WW, Chen Y, Kok KH, To KK, Yuen KY. (2019) H7N9 influenza A virus activation of necroptosis in human monocytes links innate and adaptive immune responses. Cell Death and Disease 10:442.

Lui, WY, Yuen CK, Li C, Wong WM, Lui PY, Lin CH, Chan KH, Zhao H, Chen H, To KK, Zhang AJ, Yuen KY, Kok KH. (2019) SMRT sequencing revealed the diversity and characteristics of defective interfering RNAs in influenza A (H7N9) virus infection. Emerging Microbes & Infections 8:662-674.

Zhu Z, Chu H, Wen L, Yuan S, Chik KK, Yuen TT, Yip CC, Wang D, Zhou J, Yin F, Jin DY, Kok KH, Yuen KY, Chan JF. (2019) Targeting SUMO Modification of the Non-Structural Protein 5 of Zika Virus as a Host-Targeting Antiviral Strategy. Int J Mol Sci. 20. pii: E392.

Yuan S, Chu H, Chan JF, Ye ZW, Wen L, Yan B, Lai PM, Tee KM, Huang J, Chen D, Li C, Zhao X, Yang D, Chiu MC, Yip C, Poon VK, Chan CC, Sze KH, Zhou J, Chan IH, Kok KH, To KK, Kao RY, Lau JY, Jin DY, Perlman S, Yuen KY. (2019) SREBP-dependent lipidomic reprogramming as a broad-spectrum antiviral target. Nat Commun. 10:120.

Lau SKP, Fan RYY, Luk HKH, Zhu L, Fung J, Li KSM, Wong EYM, Ahmed SS, Chan JFW, Kok RKH, Chan KH, Wernery U, Yuen KY, Woo PCY. (2018) Replication of MERS and SARS coronaviruses in bat cells offers insights to their ancestral origins. Emerg Microbes Infect. 7:209.

Yeung ML, Jia L, Yip CCY, Chan JFW, Teng JLL, Chan KH, Cai JP, Zhang C, Zhang AJ, Wong WM, Kok KH, Lau SKP, Woo PCY, Lo JYC, Jin DY, Shih SR, Yuen KY. (2018) Human tryptophanyl-tRNA synthetase is an IFN-γ-inducible entry factor for Enterovirus. J Clin Invest. 128:5163-5177.

Wang PH, Ye ZW, Deng JJ, Siu KL, Gao WW, Chaudhary V, Cheng Y, Fung SY, Yuen KS, Ho TH, Chan CP, Zhang Y, Kok KH, Yang W, Chan CP, Jin DY. (2018) Inhibition of AIM2 inflammasome activation by a novel transcript isoform of IFI16. EMBO Rep. 19. pii: e45737

Zhao H, To KK, Chu H, Ding Q, Zhao X, Li C, Shuai H, Yuan S, Kok KH, Jiang S, Yuen KY. (2018) Dual-functional peptide with defective interfering genes effectively protects mice against avian and seasonal influenza. Nat Commun. 9:2358.

Guo Q, Chan JF, Poon VK, Wu S, Chan CC, Hou L, Yip CC, Ren C, Cai JP, Zhao M, Zhang AJ, Song X, Chan KH, Wang B, Kok KH, Wen Y, Yuen KY, Chen W. (2018) Immunization with a Novel Human type 5 Adenovirus-Vectored Vaccine Expressing the Premembrane and Envelope Proteins of Zika Virus Provides Consistent and Sterilizing Protection in Multiple Immunocompetent and Immunocompromised Animal Models. J Infect Dis.218:365-377.

Wang PH, Fung SY, Gao WW, Deng JJ, Cheng Y, Chaudhary V, Yuen KS, Ho TH, Chan CP, Zhang Y, Kok KH, Yang W, Chan CP, Jin DY. (2018) A novel transcript isoform of STING that sequesters cGAMP and dominantly inhibits innate nucleic acid sensing. Nucleic Acids Res. 46:4054-4071.

Chan CP, Yuen CK, Cheung PH, Fung SY, Lui PY, Chen H, Kok* KH, Jin DY. (2018) Antiviral activity of double-stranded RNA-binding protein PACT against influenza A virus mediated via suppression of viral RNA polymerase. FASEB J. 32:4380-4393. (*: co-corresponding author)

Lau SKP, Zhang L, Luk HKH, Xiong L, Peng X, Li KSM, He X, Zhao PS, Fan RYY, Wong ACP, Ahmed SS, Cai JP, Chan JFW, Sun Y, Jin D, Chen H, Lau TCK, Kok KH, Li W, Yuen KY, Woo PCY. (2018) Receptor usage of a novel bat lineage C betacoronavirus reveals evolution of MERS-related coronavirus spike proteins for human DPP4 binding. J Infect Dis. 218:197-207

Lui PY, Wong LR, Ho TH, Au SWN, Chan CP, Kok* KH, Jin DY. (2017) PACT Facilitates RNA-Induced Activation of MDA5 by Promoting MDA5 Oligomerization. J Immunol. 199:1846-55. (*: co-corresponding author)

Chaudhary V, Yuen KS, Chan JF, Chan CP, Wang PH, Cai JP, Zhang S, Liang MF, Kok KH, Chan CP, Yuen KY, Jin DY (2017) Selective activation of Type II Interferon signaling by Zika virus NS5 protein. J Virol. 96:3204-11.

Cheung NN, Lai KK, Dai J, Kok KH, Chen H, Chan KH, Yuen KY, Kao R. (2017) Broad-spectrum inhibition of common respiratory RNA viruses by a pyrimidine synthesis inhibitor with involvement of the host antiviral response. J Gen Virol. 98:946-54.

Yuen KS, Chan CP, Kok KH, Jin DY. (2017) Mutagenesis and Genome Engineering of Epstein - Barr virus in Cultured Human Cells by CRISPR/Cas9. Methods Mol Biol. 1498:23-31.

Chan JF, Zhang AJ, Chan CC, Yip CC, Mak WW, Zhu H, Poon VK, Tee KM, Zhu Z, Cai JP, Tsang JO, Chik KK, Yin F, Chan KH, Kok KH, Jin DY, Au-Yeung RK, Yuen KY. (2016) Zika Virus Infection in Dexamethasone-immunosuppressed Mice Demonstrating Disseminated Infection with Multi-organ Involvement Including Orchitis Effectively Treated by Recombinant Type I Interferons. EBioMedicine. 14:112-122.

Chan JF, Yip CC, Tsang JO, Tee KM, Cai JP, Chik KK, Zhu Z, Chan CC, Choi GK, Sridhar S, Zhang AJ, Lu G, Chiu K, Lo AC, Tsao SW, Kok KH, Jin DY, Chan KH, Yuen KY. (2016) Differential cell line susceptibility to the emerging Zika virus: implications for disease pathogenesis, non-vector-borne human transmission and animal reservoirs. Emerg Microbes Infect. 5:e93.

Yuen CK, Chan CP, Fung SY, Wang PH, Wong WM, Tang HM, Yuen KS, Chan CP, Jin DY, Kok KH. (2016) Suppression of Type I Interferon Production by Human T-Cell Leukemia Virus Type 1 Oncoprotein Tax through Inhibition of IRF3 Phosphorylation. J Virol. 90:3902-12.

Ho TH, Kew C, Lui PY, Chan CP, Satoh T, Akira S, Jin DY, Kok KH. (2015) PACT- and RIG-I-Dependent Activation of Type I Interferon Production by a Defective Interfering RNA Derived from Measles Virus Vaccine. J Virol. 90:1557-68.

Chaudhary V, Zhang S, Yuen KS, Li C, Lui PY, Fung SY, Wang PH, Chan CP, Li D, Kok KH, Liang M, Jin DY. (2015) Suppression of type I and type III IFN signalling by NSs protein of severe fever with thrombocytopenia syndrome virus through inhibition of STAT1 phosphorylation and activation. J Gen Virol. 96:3204-11.

Yuen KS, Chan CP, Wong NH, Ho CH, Ho TH, Lei T, Deng W, Tsao SW, Chen H, Kok* KH, Jin DY. (2014) CRISPR/Cas9-mediated genome editing of Epstein-Barr virus in human cells. J Gen Virol. 96:626-36. (*: co-corresponding author)

Lee SMY, Kok KH, Jaume M, Cheung TKW, Yip TF, Lai JCC, Guan Y, Webster RG, Jin DY, Peiris JSM. (2014) Toll-like receptor 10 is involved in induction of innate immune responses to influenza virus infection. Proc Natl Acad Sci USA 111:3793-8.

Siu* KL, Yeung* ML, Kok* KH, Yuen KS, Kew C, Lui PY, Chan CP, Tse H, Woo PC, Yuen KY, Jin DY. (2014) Middle East respiratory syndrome coronavirus 4a protein is a double-stranded RNA-binding protein that suppresses PACT-induced activation of RIG-I and MDA5 in innate antiviral response. J Virol 88:4866-4876. (*: co-first author)

Siu KL, Chan CP, Kok KH, Woo PCY, Jin DY. (2014) Suppression of innate antiviral response by severe acute respiratory syndrome coronavirus M protein is mediated through the first transmembrane domain. Cell Mol Immunol 11:141-149.

Kew C, Lui PY, Chan CP, Au WN, Mohr I, Jin DY, Kok KH. (2013) Suppression of PACT-induced type I interferon production by herpes simplex virus type 1 Us11 protein. J Virol 87:13141-13149.

Lei T, Yuen KS, Tsao SW, Chen H, Kok KH, Jin DY. (2013) Perturbation of biogenesis and targeting of Epstein-Barr virus-encoded miR-BART3 microRNA by adenosine-to-inosine editing. J Gen Virol 12:2739-2744.

Kok KH, Jin DY. (2013) Balance of power in host-virus arms races. Cell Host Microbe 14:5-6.

Kok KH, Lui PY, Ng MHJ, Siu KL, Au SWN, Jin DY. (2011) The double-stranded RNA-binding protein PACT functions as a cellular activator of RIG-I to facilitate innate antiviral response. Cell Host Microbe 9:299-309.

Editorship:

Associate Editor, Journal of Medical Virology (2022-present)

Academic Editor, PLoS ONE (2010 - present)