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03 Apr 2020

Chris Mok and team to publish in Science to provide molecular insights into antibody recognition of SARS-CoV-2

Chris Mok, team leader at HKU-Pasteur, published in Science with his team and with colleagues from Scripps Research Institute, USAproviding molecular insights into antibody recognition of SARS-CoV-2:

>>> A highly conserved cryptic epitope in the receptor-binding domains of SARS-CoV-2 and SARS-CoV

This paper sheds new light into antibody recognition of SARS-CoV-2. To this end, they used the Receptor Binding Domain (RBD) of the Spike protein of SARS-CoV-2, which is the region of the Spike protein that allows virus entry into cells by interacting with its specific receptor.  

They took advantage of CR3022, a neutralizing monoclonal antibody previously isolated from a convalescent SARS patient, to determine its crystal structure in complex with the RBD of the SARS-CoV-2 Spike protein. This antibody targets a highly conserved epitope that enables cross-reactive binding with the Spike proteins of both SARS-CoV and SARS-CoV-2. Structural alignment of the CR3022-SARS-CoV-2 RBD complex with the ACE2-SARS-CoV RBD complex further indicates that binding of CR3022 would not clash with ACE2.  

This analysis implies that the neutralization mechanism of CR3022 for SARS-CoV does not depend on direct blocking of receptor binding, which is consistent with the observation that CR3022 does not compete with ACE2 for binding to the RBD. Overall, this study provides insight into how SARS-CoV-2 can be targeted by the humoral immune response and revealed a conserved, but cryptic epitope shared between SARS-CoV-2 and SARS-CoV.

27 Mar 2020

Cross-reactive antibody response between SARS-CoV-2 and SARS-CoV infections by Chris Mok and Tomas Lyu

Chris Mok, Tomas Lyu and their team published with Malik Peiris, Leo Poon and fellow colleagues from SCRIPPS Research Institute, USA, their findings on antibody response of SARS-CoV-2 in bioRxiv

Cross-reactive antibody response between SARS-CoV-2 and SARS-CoV infections

Abstract: The World Health Organization has recently declared the ongoing outbreak of COVID-19, which is caused by a novel coronavirus SARS-CoV-2, as pandemic. There is currently a lack of knowledge in the antibody response elicited from SARS-CoV-2 infection. One major immunological question is concerning the antigenic differences between SARS-CoV-2 and SARS-CoV. We address this question by using plasma from patients infected by SARS-CoV-2 or SARS-CoV, and plasma obtained from infected or immunized mice. Our results show that while cross-reactivity in antibody binding to the spike protein is common, cross-neutralization of the live viruses is rare, indicating the presence of non-neutralizing antibody response to conserved epitopes in the spike. Whether these non-neutralizing antibody responses will lead to antibody-dependent disease enhancement needs to be addressed in the future. Overall, this study not only addresses a fundamental question regarding the antigenicity differences between SARS-CoV-2 and SARS-CoV, but also has important implications in vaccine development.

 

20 Feb 2020

SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients

Malik Peiris, Co-Director at HKU-Pasteur, published in The New England Journal Of Medicine on SARS-CoV-2 viral load in upper respiratory specimens of infected patients: 

>>> Link to the online publication 

The findings provided in this publication are in concordance with reports that transmission may occur early in the course of infection and suggest that case detection and isolation may require strategies different from those required for the control of SARS-CoV.

How SARS-CoV-2 viral load correlates with culturable virus needs to be determined. Identification of patients with few or no symptoms and with modest levels of detectable viral RNA in the oropharynx for at least 5 days suggests that we need better data to determine transmission dynamics and inform our screening practices.

 

13 Feb 2020

[UPDATED] 2019nCov: List of HKU-Pasteur Research Pole’s Papers on Coronaviruses

Coronaviruses have been at the core of our work at HKU-Pasteur Research Pole since the SARS outbreak in 2003:

>>> Download our list of papers <<<

Publications on SARS:

Zhang XW, Yap YL, Altmeyer RM.
Eur J Med Chem. 2005 Jan;40(1):57-62. PMID: 15642409
 
Nal B, Chan C, Kien F, Siu L, Tse J, Chu K, Kam J, Staropoli I, Crescenzo-Chaigne B, Escriou N, van der Werf S, Yuen KY, Altmeyer R.
J Gen Virol. 2005 May;86(Pt 5):1423-34. PMID: 15831954
 
Kam YW, Kien F, Roberts A, Cheung YC, Lamirande EW, Vogel L, Chu SL, Tse J, Guarner J, Zaki SR, Subbarao K, Peiris M, Nal B, Altmeyer R.
Vaccine. 2007 Jan 8;25(4):729-40. Epub 2006 Aug 22. PMID: 17049691
 
Siu YL, Teoh KT, Lo J, Chan CM, Kien F, Escriou N, Tsao SW, Nicholls JM, Altmeyer R, Peiris JS, Bruzzone R, Nal B.
J Virol. 2008 Nov;82(22):11318-30. Epub 2008 Aug 27. PMID: 18753196.
 
Chu D. K. W., Peiris J. S. M., Chen H., Guan Y. and Poon L. L. M.
J Gen Virol 2008, 89, 1282-1287. PMID: 18420807.
 
Kam YW, Okumura Y, Kido H, Ng LF, Bruzzone R, Altmeyer R.
PLoS One. 2009 Nov 17;4(11):e7870. doi: 10.1371/journal.pone.0007870. PMID: 19924243
 
Keng CT, Akerström S, Leung CS, Poon LL, Peiris JS, Mirazimi A, Tan YJ.
Microbes Infect. 2010 Oct 28. [Epub ahead of print]. PMID: 21035562.
 
Teoh KT, Siu YL, Chan WL, Schlüter MA, Liu CJ, Peiris JS, Bruzzone R, Margolis B, Nal B.
Mol Biol Cell. 2010 Sep 22. [Epub ahead of print]. PMID: 20861307.
 
Chu DK, Leung CY, Gilbert M, Joyner PH, Ng EM, Tse TM, Guan Y, Peiris JS, Poon LL.
J Virol. 2011 Dec;85(23):12815-20. Epub 2011 Sep 28. PMID: 21957308.
 
Jaume M, Yip MS, Cheung CY, Leung HL, Li PH, Kien F, Dutry I, Escriou N, Altmeyer R, Nal B, Daëron M, Bruzzone R, Peiris JS.
J Virol. 2011 Jul 20. [Epub ahead of print]. PMID: 21775467.
 
Millet JK, Kien F, Cheung CY, Siu YL, Chan WL, Li H, Leung HL, Jaume M, Bruzzone R, Peiris JSM, Altmeyer RM, Nal B.
PLoS ONE: Research Article, published 21 Nov 2012 10.1371/journal.pone.0049566. PMID: 23185364.
 
Mesel-Lemoine M, Millet J, Vidalain PO, Law H, Vabret A, Lorin V, Escriou N, Albert ML, Nal B, Tangy F.
J Virol. 2012 Jul;86(14):7577-87. Epub 2012 May 2. PMID: 22553325.
 
Jaume M, Yip MS, Kam YW, Cheung CY, Kien F, Roberts A, Li PH, Dutry I, Escriou N, Daeron M, Bruzzone R, Subbarao K, Peiris JS, Nal B, Altmeyer R.
Hong Kong Med J. 2012 Feb;18 Suppl 2:31-6. PMID 22311359.
 
Yip MS, Leung HL, Li PH, Cheung CY, Dutry I, Li D, Daëron M, Bruzzone R, Peiris JS, Jaume M
Hong Kong Med J. 2016 Jun;22(3 Suppl 4):25-31 PMID: 27390007
 
Yip MS, Leung NH, Cheung CY, Li PH, Lee HH, Daëron M, Peiris JS, Bruzzone R, Jaume M.
Virol J 11:82 PMID: 24885320 PMCID: PMC4018502 DOI: 10.1186/1743-422X-11-82
 
Taylor A, Foo SS, Bruzzone R, Vu LD, King NJ, Mahalingam S
Immunol Rev 268:340-364 PMID: 26497532 DOI: 10.1111/imr.12367
 

Publications on MERS:

Hemida M, Perera R, Wang P, Alhammadi M, Siu L, Li M, Poon L, Saif L, Alnaeem A, Peiris M (2013)
Euro Surveill 18:20659. PMID: 24342517
 
Perera RA, Wang P, Gomaa MR, El-Shesheny R, Kandeil A, Bagato O, Siu LY, Shehata MM, Kayed AS, Moatasim Y, Li M, Poon LL, Guan Y, Webby RJ, Ali MA, Peiris JS, Kayali G.
Euro Surveill 18:pii=20574. PMID: 24079378
 
Hemida MG, Chu DK, Poon LL, Perera RA, Alhammadi MA, Ng HY, Siu LY, Guan Y, Alnaeem A, Peiris M (2014)
Emerg Infect Dis 20:1231-1234. PMID: 24964193
 
Hemida MG, Chu DK, Poon LL, Perera RA, Alhammadi MA, Ng HY, Siu LY, Guan Y, Alnaeem A, Peiris M (2014)
Euro Surveill 19(23). pii:20828. PMID: 24957744
 
Chu DK, Poon LL, Gomaa MM, Shehata MM, Perera RA, Abu Zeid D, El Rifay AS, Siu LY, Guan Y, Webby RJ, Ali MA, Peiris M, Kayali G (2014)
Emerg Infect Dis 20:1049-1053. PMID: 24957744
 
Chan SM*, Damdinjav B*, Perera RA*, Chu DK*, Khishgee B, Enkhbold B, Poon LL, Peiris M
Emerg Infect Dis. 2015 Jul;21(7):1269-71. doi: 10.3201/eid2107.150178. PMID: 26080032
 
Memish ZA, Alsahly A, Masri MA, Heil GL, Anderson BD, Peiris M, Khan SU, Gray GC (2014)
Influenza Other Respir Viruses.9(2):64-7. PMID: 25470665
 
Van Kerkhove MD, Peiris MJ, Malik MR, Ben Embarek P
Clin Infect Dis. 2016 Oct 15;63(8):1142 PMID: 27432840
 
Funk AL, Goutard FL, Miguel E, Bourgarel M, Chevalier V, Faye B, Peiris JS, Van Kerkhove MD, Roger FL
Front Vet Sci. 2016 Oct 5;3:88 PMID: 27761437
 
So RT, Perera RA, Oladipo JO, Chu DK, Kuranga SA, Chan KH, Lau EH, Cheng SM, Poon LL, Webby RJ, Peiris M
Euro Surveill. 2018 Aug;23(32) PMID: 30107872 PMCID: PMC6092911 DOI: 10.2807/1560-7917.ES.2018.23.32.1800175
 
Chu DKW, Hui KPY, Perera RAPM, Miguel E, Niemeyer D, Zhao J, Channappanavar R, Dudas G, Oladipo JO, Traoré A, Fassi-Fihri O, Ali A, Demissié GF, Muth D, Chan MCW, Nicholls JM, Meyerholz DK, Kuranga SA, Mamo G, Zhou Z, So RTY, Hemida MG,Webby RJ, Roger F, Rambaut A, Poon LLM, Perlman S, Drosten C, Chevalier V, Peiris M
Proc Natl Acad Sci U S A. 2018 Mar 20 PMID: 29507189 PMCID: PMC5866576 DOI: 10.1073/pnas.1718769115
 
Abbad A, Perera RA, Anga L, Faouzi A, Minh NNT, Malik SMMR, Iounes N, Maaroufi A, Van Kerkhove MD, Peiris M, Nourlil J.
Euro Surveill. 2019 Nov;24(48). doi: 10.2807/1560-7917.ES.2019.24.48.1900244. PMID: 31796154
 
 

12 Feb 2020

Chris Mok’s New Publication Enlighten Us About Coronaviruses Mutations

Coronaviruses are a major public health concern, especially right now, in the middle of the “2019nCoV” outbreak. Understanding their mechanism is the core of Chris Mok’s current research. 
 
The HKU-Pasteur team leader, and his colleagues from the State Key Laboratory of Respiratory Disease, Hospital of Guangzhou Medical University and the Institute of Infectious Disease, just published on the HCoV-NL63 coronavirus that arose in 2018 in Guangzhou. 
 
They show that a previously innocuous coronavirus, NL63, was mutating and being responsible of severe acute respiratory diseases. Twenty-three hospitalized children were confirmed to be HCoV-NL63 positive, and most of whom were hospitalized with severe pneumonia or acute bronchitis. 
 
 
Wang Y, Li X, Liu W, Gan M, Zhang L, Wang J, Zhang Z, Zhu A, Li F, Sun J, Zhang 1, Zhuang Z, Luo J, Chen D, Qiu S, Zhang L, Xu D, Mok CKP, Zhang F, Zhao J, Zhou R, Zhao J
 
PMID: 31996093 DOI: 10.1080/22221751.2020.1717999
 

12 Feb 2020

Congratulations To Akhee Sabiha Jahan For The Publication Of Her Thesis!

We are very happy to see Akhee Sabiha Jahan's great work published in Cell Reports after years of effort! Under the supervision of Sumana Sanyal, Akhee's work illustrates the role of deubiquitylases during influenza infection and immune response. 

>>> OTUB1 Is a Key Regulator of RIG-I-Dependent Immune Signaling and Is Targeted for Proteasomal Degradation by Influenza A NS1

Jahan AS, Biquand E, Muñoz-Moreno R, Le Quang A, Mok CK, Wong HH, Teo QW, Valkenburg SA, Chin AWH, Man Poon LL, Te Velthuis A, García-Sastre A, Demeret C, Sanyal S

PMID: 32023470 DOI: 10.1016/j.celrep.2020.01.015

Abstract
Deubiquitylases (DUBs) regulate critical signaling pathways at the intersection of host immunity and viral pathogenesis. Although RIG-I activation is heavily dependent on ubiquitylation, systematic analyses of DUBs that regulate this pathway have not been performed. Using a ubiquitin C-terminal electrophile, we profile DUBs that function during influenza A virus (IAV) infection and isolate OTUB1 as a key regulator of RIG-I-dependent antiviral responses. Upon infection, OTUB1 relocalizes from the nucleus to mitochondrial membranes together with RIG-I, viral PB2, and NS1. Its expression depends on competing effects of interferon stimulation and IAV-triggered degradation. OTUB1 activates RIG-I via a dual mechanism of K48 polyubiquitin hydrolysis and formation of an E2-repressive complex with UBCH5c. We reconstitute this mechanism in a cell-free system comprising [35S]IRF3, purified RIG-I, mitochondrial membranes, and cytosol expressing OTUB1 variants. A range of IAV NS1 proteins trigger proteasomal degradation of OTUB1, antagonizing the RIG-I signaling cascade and antiviral responses.
 

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