Peter Pak-Hang Cheung, Chinese University of Hong Kong

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Peter Pak-Hang Cheung

Faculty, Chinese University of Hong Kong

Research fields

Biochemistry, Cell Biology, Microbiology, Molecular Biology, Systems Biology

Personal information

Education

PhD, University of Hong Kong, 2013

Lab information

Biography
Dr Peter Cheung is currently an Assistant Dean (Research) and Assistant Professor in the Department of Chemical Pathology, Faculty of Medicine at the Chinese University of Hong Kong.

He obtained his bachelor’s and Master's degree from Queen’s University, Canada, and Western University, Canada, respectively, and his doctorate degree from The University of Hong Kong.

Dr Cheung's research interest focuses on using computational, statistical, structural, and enzymological approaches to study viral replications and prevention strategies for infectious diseases.

He is the recipient of numerous awards including the Croucher-Butterfield Ph.D. Scholarship (Croucher Foundation), Best Poster Presentation Award (The University of Hong Kong), and Finalist of the Hong Kong Young Scientist Award (Hong Kong Institution of Science).

He has published extensively in the field of computational and structural biology. His original research findings have been published as first or corresponding authors in leading international journals including those of the Lancet Microbe, BMJ, Nature Catalysis, Nucleic Acids Research, and Nature Communications.

His work has been supported by the Research Grants Committee’s General Research Fund and Collaborative Research Fund, with which he led international efforts to study viral replication of influenza and SARS-CoV-2 replication using structural, computational, and enzymology approaches. Our lab has the following research interests:

(1) Gene Replication

RNA viruses encode their RNA polymerases to replicate the viral genome. The error-prone transcription process of RNA polymerases is the main driving force for viral genetic diversity essential for adaption to and infection of the host. However, the accuracy of virus transcription must be maintained at a certain threshold for faithful gene expression and protein production. We are interested in understanding the structural basis of how viral polymerases regulate transcription accuracy in RNA viruses and the biological consequences of transcriptional errors during infection. The way virus replicate its genome does not always follow the rules present in the eukaryotic systems. We are also interested in understanding how viral genome replication is regulated. To discover new mechanisms of replication accuracy and regulation, we are developing a novel genomics platform and using Cryogenic Electron Microscopy (Cryo-EM). These fundamental insights are essential in the basic understanding of gene transcription and virus evolution and the biomedical research for the development of antiviral drugs and vaccines for emerging infectious diseases.

By discovering viruses that carry mutations at the polymerase that render the virus replication mutation defective, and hence reduced genetic diversity, we were able to generate novel vaccine variants that do not cause diseases but replicate well during the manufacturing process with no selective pressure. In addition, we employ statistical and experimental approaches to determine the efficacy of COVID-19 vaccine regimens in SARS-CoV-2 and its variants of concerns.

Scientific Milestones

Discovered the first mutation defective virus with enhanced polymerase activity, challenging the thought that mutation-defective polymerase is usually accompanied by a slower polymerase activity.
Developed that first nascent RNA sequencing technique with high sequencing accuracy that can also measure polymerase error.
Reveal the mystery of how eukaryotic polymerase can maintain transcription accuracy without compromising polymerase activity.
Discovered the first ever mutation-defective (with high replication accuracy) influenza virus.

(2) Diagnostics

We employ statistical and experimental approaches to evaluate and improve the diagnostic performances of the clinical detection of nucleic acids of influenza viruses and SARS-CoV-2. We are also developing novel technologies to enhance the sensitivity and specificity for nucleic acid detection for infectious and hereditary diseases by using biochemical and microfluidic techniques.

Scientific Milestones

We performed the first meta-analysis to demonstrate that accuracy of three types of nucleic acid tests (real time PCR, digital PCR, and LAMP) does not differ significantly. Instead, accuracy depends on specific experimental conditions, implying that more efforts should be directed to optimising the experimental setups for the nucleic acid tests.

(3) Vaccine

We employ statistical and experimental approaches to evaluate and improve the diagnostic performances of the clinical detection of nucleic acids of influenza viruses and SARS-CoV-2. We are also developing novel technologies to enhance the sensitivity and specificity for nucleic acid detection for infectious and hereditary diseases by using biochemical and microfluidic techniques.

Scientific Milestones

We performed the first meta-analysis to demonstrate that accuracy of three types of nucleic acid tests (real time PCR, digital PCR, and LAMP) does not differ significantly. Instead, accuracy depends on specific experimental conditions, implying that more efforts should be directed to optimising the experimental setups for the nucleic acid tests.

(4) Antivirals

We elucidate the mechanisms of inhibition of gene replication by NTP analog antiviral drugs. We employ structural biology and Molecular Dynamics simulation to understand at atomic level how NTP analog disrupt which step of RNA synthesis carried out by the viral polymerase.

Scientific Milestones

We were amongst the first to show that Ribavirin can inhibit live SARS-CoV-2 replication
We elucidated the mechanism at atom level how Remdesivir inhibit viral polymerase translocation.
We explained how the Favipiravir causes delayed chain termination and induces mutagenesis in viral polymerase by using structural biology and enzymology.
We discovered the first ribavirin-resistant influenza virus, and such virus was reported to be a mutation-defective virus, the first of its kind.
https://www.cuhk.edu.hk/med/cpy/Research/PeterCheung.htm

Publications

https://scholar.google.com/citations?user=vQ3AUT0AAAAJ&hl=en

LIST OF RESEARCH OUTPUTS OR CREATIVE WORKS
* denotes corresponding author

With CUHK as affiliation:
1. Li M-Y, Deng K, Cheng X-H, Siu LY-L, Gao Z-R, Naik TS, Stancheva VG, Cheung PPH, Teo Q-W, van Leur SW, Wong H-H, Lan Y, Lam TT-Y, Sun M-X, Zhang N-N, Zhang Y, Cao T-S, Yang F, Deng Y-Q, Sanyal S, Qin C-F. ARF4-mediated intracellular transport as a broad-spectrum antiviral target. Nature Microbiol. 10:710–723 (2025). [Research Article; 2022 Impact Factor: 28.3]
2. Wang Y, Liu X, Fan Y, Xie B, Cheng J, Wong K-C, Cheung P, King I, Li Y*. Predicting Drug Responses of Unseen Cell Types through Transfer Learning with Foundation Models. Nature Comput Sci. (2025). [In Press] [Research Article; 2022 Impact Factor: 11.3]
3. Suarez GD, Tang YYK, Bayer S, Cheung PPH, Nagl S*. Multiplexed detection of respiratory virus RNA using optical pH sensors and injection-molded centrifugal microfluidics. Microchimica Acta, 192(3):151 (2025). [Research Article; 2022 Impact Factor 5.7]
4. Malki Y, Kang G, Lam WKJ, Zhou Q, Cheng SH, Cheung PPH, Bai J, Chan ML, Lee CT, Peng W, Zhang Y, Gai W, Wong WWS, Ma MJL, Li W, Xu X, Gao Z, Tse IOL, Shang H, Choy LYL, Jiang P, Chan KCA, Lo YMD. Analysis of a cell-free DNA–based cancer screening cohort links fragmentomic profiles, nuclease levels, and plasma DNA concentrations. Genome Res. 35(1):31–42 (2025). [Research Article; 2022 Impact Factor: 7.0]
5. Chow NKN, Tsang CYW, Chan YH, Telaga SA, Ng LYA, Chung CM, Yip YM, Cheung PPH*. The effect of pre-COVID and post-COVID vaccination on long COVID: A systematic review and meta-analysis. Journal of Infection. 89(6):106358 (2024). [Research Article; 2022 Impact Factor: 28.2]
6. Lou J, Liang W, Cao L, Hu I, Zhao S, Chen Z, Chan RWY, Cheung PPH, Zheng H, Liu C, Li Q, Chong MKC, Zhang Y, Yeoh E, Chan PKS, Zee BCY, Mok CKP, Wang MH. Predictive evolutionary modelling for influenza virus by site-based dynamics of mutations. Nature Commun. 15:2546 (2024). [Impact Factor: 17.694]
7. Wang X, Jing X, Shi J, Liu Q, Shen S, Cheung PPH, Wu J, Deng F, Gong P. A jingmenvirus RNA-dependent RNA polymerase structurally resembles the flavivirus counterpart but with different features at the initiation phase. Nucleic Acids Research. 52(6):3278-3290 (2024). [Impact Factor: 15.0]
8. Wang X, Xu T, Yao Y, Cheung PP, Gao X, Zhang L*. SARS-CoV-2 RNA-Dependent RNA Polymerase Follows Asynchronous Translocation Pathway for Viral Transcription and Replication. J Phys Chem Lett, 14(45):10119-10128 (2023). [Research Article; 2022 Impact Factor: 5.7]
9. Suarez, G.D., Bayer S., Tang, Y.Y.K., Suarez D.A., Cheung P.P.H.* and Nagl S.* “Rapid microfluidics prototyping through variotherm desktop injection molding for multiplex diagnostics” Lab on a Chip, 2023,23, 3850-3861 [Research Article; 2022 Impact Factor: 6.1]
10. Han, W., Chen, N., Xu, X., Sun, S., Cheung, P.P.H.*, Gao, X, Predicting the antigenic evolution of SARS-CoV-2 with deep learning, Nature Communications, 14: 3478 (2023) [Research Article; 2022 Impact Factor: 17.694]
11. Huang J, Zhao S, Chong KC, Zhou Y, Lu W, Fang F, Cheung PPH, Lai KC, Hui DS, Mok CKP. Infection rate in Guangzhou after easing the zero-COVID policy: seroprevalence results to ORF8 antigen. Lancet Infect Dis., 23(4):403-404 (2023). [Research Article; 2022 Impact Factor: 56.3]
12. Au, W. Y., Cheung, P.P.H.*, Effectiveness of heterologous and homologous COVID-19 vaccine regimens: a living systematic review with network meta-analysis. British Medical Journal (BMJ), 377: e069989 (2022). [Research Article; 2022 Impact Factor: 107.7]

13. Zhou Z, Ma ML, Chan RWY, Lam WKJ, Peng W, Gai W, Hu X, Ding SC, Ji L, Zhou Q, Cheung PPH, Yu SCY, Teoh JYC, Szeto CC, Wong J, Wong VWS, Wong GLH, Chan SL, Hui EP, Ma BBY, Chan ATC, Chiu RWK, Chan KCA, Lo YMD, Fragmentation landscape of cell-free DNA revealed by deconvolutional analysis of end motifs. Proc Natl Acad Sci U S A., 120(17):e2220982120 (2023). [Research Article; 2022 Impact Factor: 11.1]
14. Au, W. Y., Ye, C., Briner S.L., Suarez, G.D., Han, J., Xu, X., Park, J.G., Brindley, M.A., Martinez-Sobrido*, L., Cheung, P.P.H.*, Systematic comparison between BNT162b2 and CoronaVac in the seroprotection against SARS-CoV-2 Alpha, Beta, Gamma, and Delta variants, Journal of Infection, DOI: 10.1016/j.jinf.2022.02.030, (2022) [Research Article; Impact Factor: 28.2]
15. Chen, M., Chan, R.W.Y., Cheung, P.P.H., Ni, M., Wong, D.K.L., Zhou, Ze, Ma, M.-J.L., Huang, L, Xu, X., Lee, W.-S., Wang, G., Lui, K.O., Lam, W.K.J., Teoh, J.Y.C., Ng, C.-F., Jiang, P., Chan, K.C.A., Chiu, R.W.K., Lo, Y.M.D, Fragmentomics of urinary cell-free DNA in nuclease knockout mouse model, PLoS Genetics, DOI 10.1371/journal.pgen.1010262 (2022). [Research Article; 2022 Impact Factor: 4.5]
16. Suarez, G.D., Suarez D.A., Tang Y.Y.K., Zhang J.-X., Li, J., Nagl, S., Cheung P.P.H.* Uncovering Mechanisms of RT-LAMP Colorimetric SARS-CoV-2 Detection to Improve Assay Reliability, Analytical Methods, DOI: 10.1039/D1AY01395E, (2022) [Research Article; 2022 Impact Factor: 3.1]
17. W. Y. Au, Cheung, P. P. H.*, Diagnostic performances of common nucleic acid tests for SARS-CoV-2 in hospitals and clinics: a systematic review and meta-analysis. The Lancet Microbe, doi:10.1016/S2666-5247(21)00214-7, (2021) [Research Article; 2022 Impact Factor: 38.2]
18. Xu, X., Zhang, L., Chu J.T.S., Wang, Y. Chin, A.W.H., Dai, Z., Poon, L.L.M., Cheung, P.P.-H.*, Huang, X.*. A Novel Mechanism of Enhanced Transcription Activity and Fidelity for Influenza A Viral RNA-dependent RNA Polymerase, Nucleic Acids Research, 49 (15), 8796 (2021). [Research Article; 2022 Impact Factor: 15.0]
19. Wang, Y., Yuan, C., Xu, X., Chong, T.H., Zhang, L., Cheung P.P.H.*, Huang, X.*. The mechanism of action of T-705 as a unique delayed chain terminator on influenza viral polymerase transcription, Biophysical Chemistry, 277, 106652, (2021). [Research Article; 2022 Impact Factor: 3.628]

With HKUST as affiliation:
20. Zhang, L., Zhang, D., Wang X., Yuan, X., Li, Y., Jia, X., Gao, X., Yen, Y., Cheung, P.P.*, Huang, X.*, 1’-Ribose Cyano Substitution Allows Remdesivir to Effectively Inhibit both Nucleotide Addition and Proofreading during SARS-CoV-2 Viral RNA Replication, Physical Chemistry Chemical Physics, 23, 5852 (2021). [Research Article; 2022 Impact Factor: 3.3]
21. Choy, K., Wong, A., Kaewpreedee, P., Sia, S., Chen, D., Hui, K., Chu, D., Chan, M., Cheung, P., Huang, X., Peiris, M., Yen, H-L, Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro, Antiviral Research, 178: 104786, (2020) [Research Article; 2022 Impact Factor 7.6]
22. Unarta, I.S., Cao, S., Kubo, S., Wang, W., Cheung, P.P.H., Gao, X., Takada, S., Huang, X.* Role of Bacterial RNA Polymerase Gate Opening Dynamics in DNA Loading and Antibiotics Inhibition Elucidated by quasi-Markov State Model, Proc. Nat. Acad. Sci. U.S.A., 118(17), e2024324118, (2021) [Research Article; Impact Factor: 11.1]
23. Wang, Y., Chong, T.H, Unarta, I.C., Xu, X., Suarez, G.D., Wang, J., Lis, J.T., Huang, X., Cheung, P.P.*, EmPC-Seq: Accurate RNA-sequencing and Bioinformatics Platform to Map RNA Polymerases and Remove Background Error, Bio-Protocol, 11, 4 (2021) [Research Article; 2022 Impact Factor: 0.8]
24. Wang, X., Unarta, I.C., Cheung P.P.H., Huang, X.* Elucidating Molecular Mechanisms of Functional Conformational Changes of Proteins via Markov State Models, Curr. Opin. Struct. Biol, 67, 69-77, (2021) [Review Article: 2022 Impact Factor: 6.8]
25. Cheung, P.P.H., Jiang, B., Booth, G.T., Chong, T.H., Unartar, I.C., Wang, Y., Suarez, G.D., Wang, J., Lis, J.T., Huang, X., Identifying Transcription Error-Enriched Genomic Loci Using Nuclear Run-On Circular-Sequencing Coupled with Background Error Modeling, Journal of Molecular Biology, S0022-2836(20)30284-9, (2020) [Research Article; Impact Factor: 5.6]
26. Tse, K.M., Xu, J., Xu, L., Sheong, F.K., Wang, S., Chow, H.Y., Gao, X., Li, X., Cheung, P.P.H.*, Wang, D.*, Zhang, Y.*, Huang, X*. Intrinsic cleavage of RNA polymerase II adopts a nucleobase-independent mechanism assisted by transcript phosphate, Nature Catalysis, 2, 228–235 (2019) [Research Article; 2022 Impact Factor: 37.8]
27. Wang, L., Chen, J., Zeng, X., Cheung, P.P.H., Zheng, X., Xie, L., Shi, X., Ren, L., Huang, X., Wang, Y. Mechanistic Insights and Rational Design of a Versatile Surface with Cells/Bacteria Recognition Capability via Orientated Fusion Peptides, Advanced Science, 6 (9), 1801827, (2019). [Research Article; 2022 Impact Factor: 15.1]
28. Lei, J., Sheng, G., Cheung, P.P.H., Wang, S., Li, Y., Gao, X., Zhang, Y., Wang, Y., Huang, X. Two symmetric arginine residues play distinct roles in Thermus thermophilus Argonaute DNA guide strand-mediated DNA target cleavage. Proc. Nat. Acad. Sci. U.S.A., 116 (3), 845-853, (2019). [Research Article; Impact Factor: 11.1]
29. Jiang, L., Cao, S., Cheung, P.P.H., Zheng, X., Leung, C.W.T., Peng, Q., Shuai, Z., Tang, B.Z., Yao, S., Huang, X., Real-Time Monitoring of Hydrophobic Aggregation Reveals a Critical Role of Cooperativity in Hydrophobic Effect, Nature Communications, 8, 15639, (2017) [Research Article; Impact Factor: 17.694]
30. Zhang, L., Pardo, F., Unarta, I.C., Cheung, P.P.H., Wang, G., Wang, D., and Huang, X. Elucidation of the Dynamics of Transcription Elongation by RNA Polymerase II using Kinetic Network Models, Accounts of Chemical Research, 49 (4), 687–694, (2016) [Research Article; Impact Factor: 18.3]
31. Zhang, L., Jiang, H., Sheong, F.K., Pardo-Avila, F., Cheung, P.P.H., Huang, X., Constructing Kinetic Network Models to Elucidate Mechanisms of Functional Conformational Changes of Enzymes and their Recognition with Ligands, Methods in Enzymology, 578, 343–371, (2016) [Book Chapter; 2021 Impact Factor: 1.682]

With HKU as affiliation:
32. Luk, G.S., Leung, C.Y., Sia, S.F., Choy, K.T., Zhou, J., Ho, C.C., Cheung, P.P., Lee, E.F., Wai, C.K., Li, P.C., et al., Transmission of H7N9 influenza viruses with polymorphism at PB2 residue 627 in chickens and ferrets. Journal of Virology, 89 (19), 9939, (2015) [Research Article; 2022 Impact Factor: 5.4]
33. Cheung, P.P., Rogozin, I.B., Choy, K.T., Ng, H.Y., Peiris, J.S., and Yen, H.L Comparative mutational analyses of influenza A viruses. RNA 21, 36, (2015) [Research Article; 2022 Impact Factor: 4.5]
34. Cheung, P.P., Watson, S.J., Choy, K.T., Fun Sia, S., Wong, D.D., Poon, L.L., Kellam, P., Guan, Y., Malik Peiris, J.S., and Yen, H.L. Generation and characterization of influenza A viruses with altered polymerase fidelity. Nature Communications 5, 4794, (2014). [Research Article; 2022 Impact Factor: 17.694]
35. Leung, Y.H., Nicholls, J.M., Ho, C.K., Sia, S.F., Mok, C.K., Valkenburg, S.A., Cheung, P.P., Hui, K.P., Chan, R.W., Guan, Y., et al., Highly pathogenic avian influenza A H5N1 and pandemic H1N1 virus infections have different phenotypes in Toll-like receptor 3 knockout mice. Journal of General Virology 95, 1870-1879, (2014) [Research Article; 2022 Impact Factor: 3.8]
36. Yen, H.L., McKimm-Breschkin, J.L., Choy, K.T., Wong, D.D., Cheung, P.P., Zhou, J., Ng, I.H., Zhu, H., Webby, R.J., Guan, Y., et al., Resistance to neuraminidase inhibitors conferred by an R292K mutation in a human influenza virus H7N9 isolate can be masked by a mixed R/K viral population. mBio 4, (2013) [Research Article; 2022 Impact Factor: 6.4]
37. Wong, D.D., Choy, K.T., Chan, R.W., Sia, S.F., Chiu, H.P., Cheung, P.P., Chan, M.C., Peiris, J.S., and Yen, H.L, Comparable fitness and transmissibility between oseltamivir-resistant pandemic 2009 and seasonal H1N1 influenza viruses with the H275Y neuraminidase mutation. Journal of Virology 86, 10558, (2012) [Research Article; 2022 Impact Factor: 5.4]
38. Yen, H.L., Liang, C.H., Wu, C.Y., Forrest, H.L., Ferguson, A., Choy, K.T., Jones, J., Wong, D.D., Cheung, P.P., Hsu, C.H., et al., Hemagglutinin-neuraminidase balance confers respiratory-droplet transmissibility of the pandemic H1N1 influenza virus in ferrets. Proc. Nat. Acad. Sci. U.S.A.108, 14264, (2011) [Research Article; 2022 Impact Factor: 11.1]
39. Cheung, P.P., Leung, Y.H., Chow, C.K., Ng, C.F., Tsang, C.L., Wu, Y.O., Ma, S.K., Sia, S.F., Guan, Y., and Peiris, J.S., Identifying the species-origin of faecal droppings used for avian influenza virus surveillance in wild-birds. Journal of Clinical Virology 46, 90, (2009) [Research Article; Impact Factor: 14.481]

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