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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity
Nature, Volume 603, No. 7902, Year 2022
Notification
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Description
The SARS-CoV-2 Omicron BA.1 variant emerged in 20211 and has multiple mutations in its spike protein2. Here we show that the spike protein of Omicron has a higher affinity for ACE2 compared with Delta, and a marked change in its antigenicity increases Omicron’s evasion of therapeutic monoclonal and vaccine-elicited polyclonal neutralizing antibodies after two doses. mRNA vaccination as a third vaccine dose rescues and broadens neutralization. Importantly, the antiviral drugs remdesivir and molnupiravir retain efficacy against Omicron BA.1. Replication was similar for Omicron and Delta virus isolates in human nasal epithelial cultures. However, in lung cells and gut cells, Omicron demonstrated lower replication. Omicron spike protein was less efficiently cleaved compared with Delta. The differences in replication were mapped to the entry efficiency of the virus on the basis of spike-pseudotyped virus assays. The defect in entry of Omicron pseudotyped virus to specific cell types effectively correlated with higher cellular RNA expression of TMPRSS2, and deletion of TMPRSS2 affected Delta entry to a greater extent than Omicron. Furthermore, drug inhibitors targeting specific entry pathways3 demonstrated that the Omicron spike inefficiently uses the cellular protease TMPRSS2, which promotes cell entry through plasma membrane fusion, with greater dependency on cell entry through the endocytic pathway. Consistent with suboptimal S1/S2 cleavage and inability to use TMPRSS2, syncytium formation by the Omicron spike was substantially impaired compared with the Delta spike. The less efficient spike cleavage of Omicron at S1/S2 is associated with a shift in cellular tropism away from TMPRSS2-expressing cells, with implications for altered pathogenesis. © 2022, The Author(s).
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC8942856/bin/41586_2022_4474_MOESM1_ESM.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC8942856/bin/41586_2022_4474_MOESM2_ESM.pdf
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https://efashare.b-cdn.net/share/pmc/articles/PMC8942856/bin/41586_2022_4474_MOESM4_ESM.xlsx
https://efashare.b-cdn.net/share/pmc/articles/PMC8942856/bin/41586_2022_4474_MOESM5_ESM.xlsx
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https://efashare.b-cdn.net/share/pmc/articles/PMC8942856/bin/41586_2022_4474_MOESM7_ESM.xlsx
https://efashare.b-cdn.net/share/pmc/articles/PMC8942856/bin/41586_2022_4474_MOESM8_ESM.xlsx
https://efashare.b-cdn.net/share/pmc/articles/PMC8942856/bin/41586_2022_4474_MOESM9_ESM.xlsx
Authors & Co-Authors
Meng, Bo
United Kingdom, Cambridge
University of Cambridge
Abdullahi, Adam
United Kingdom, Cambridge
University of Cambridge
Ferreira, Isabella A.T.M.
United Kingdom, Cambridge
University of Cambridge
Saito, Akatsuki
Japan, Miyazaki
University of Miyazaki
Kimura, Izumi
Japan, Tokyo
The University of Tokyo
Yamasoba, Daichi
Japan, Tokyo
The University of Tokyo
Fatihi, Saman
India, New Delhi
Council of Scientific and Industrial Research India
Papa, Guido
United Kingdom, Cambridge
The Medical Research Council Laboratory of Molecular Biology
Kemp, Steven A.
United Kingdom, Cambridge
University of Cambridge
Ikeda, Terumasa
Japan, Kumamoto
Kumamoto University
Toyoda, Mako
Japan, Kumamoto
Kumamoto University
Tan, Toong Seng
Japan, Kumamoto
Kumamoto University
Kuramochi, Jin
Japan, Utsunomiya
Kuramochi Clinic Interpark
Ueno, Takamasa
Japan, Kumamoto
Kumamoto University
Shirakawa, Kotaro
Japan, Kyoto
Kyoto University
Takaori-Kondo, Akifumi
Japan, Kyoto
Kyoto University
Charles, Oscar J.
United Kingdom, London
University College London
Baker, Stephen G.
United Kingdom, Cambridge
University of Cambridge
Dougan, Gordon J.
United Kingdom, Cambridge
University of Cambridge
Hess, Christoph
United Kingdom, Cambridge
University of Cambridge
Kingston, Nathalie
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
United Kingdom, Cambridge
University of Cambridge
Lehner, P. Joseph
United Kingdom, Cambridge
University of Cambridge
Lyons, Paul A.
United Kingdom, Cambridge
University of Cambridge
Matheson, Nicholas J.
United Kingdom, Cambridge
University of Cambridge
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
United Kingdom, Bristol
Nhs Blood and Transplant
Ouwehand, Willem Hendrik
United Kingdom, Cambridge
University of Cambridge
Saunders, Caroline
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
Summers, Charlotte
United Kingdom, Cambridge
University of Cambridge
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
Toshner, Mark R.
United Kingdom, Cambridge
University of Cambridge
Weekes, Michael P.
United Kingdom, Cambridge
University of Cambridge
Shaw, Ashley S.
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
Bucke, Ashlea
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
Calder, Jo
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
Canna, Laura
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
Domingo, Jason
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
Elmer, Anne
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
Harris, Julie
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
Hewitt, Sarah
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
Kennet, Jane
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
Jose, Sherly
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
Kourampa, Jenny
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
Meadows, Anne
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
Price, Jane
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
Rastall, Rebecca J.
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
Ribeiro, Carla G.
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
Rowlands, Jane
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
Tordesillas, Hugo
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
Dunmore, Benjamin J.
United Kingdom, Cambridge
University of Cambridge
Huang, Christopher L.H.
United Kingdom, Cambridge
University of Cambridge
Mescia, Federica
United Kingdom, Cambridge
University of Cambridge
Gleadall, Nicholas S.
United Kingdom, Cambridge
University of Cambridge
Jarvis, Isobel
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
Turner, Lori
United Kingdom, Cambridge
University of Cambridge
Chinnery, Patrick Francis
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
United Kingdom, Cambridge
University of Cambridge
United Kingdom, Cambridge
Mrc Mitochondrial Biology Unit
Dewhurst, Eleanor F.
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
United Kingdom, Cambridge
University of Cambridge
Papadia, Sofia
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
United Kingdom, Cambridge
University of Cambridge
Penkett, Christopher J.
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
United Kingdom, Cambridge
University of Cambridge
Sambrook, Jennifer G.
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
United Kingdom, Cambridge
University of Cambridge
Schon, Katherine R.
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
United Kingdom, Cambridge
University of Cambridge
Stirrups, Kathleen E.
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
United Kingdom, Cambridge
University of Cambridge
Townsend, Paul A.
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
United Kingdom, Cambridge
University of Cambridge
Butlertanaka, Erika P.
Japan, Miyazaki
University of Miyazaki
Tanaka, Yuri L.
Japan, Miyazaki
University of Miyazaki
Ito, Jumpei
Japan, Tokyo
The University of Tokyo
Uriu, Keiya
Japan, Tokyo
The University of Tokyo
Kosugi, Yusuke
Japan, Tokyo
The University of Tokyo
Suganami, Mai
Japan, Tokyo
The University of Tokyo
Oide, Akiko
Japan, Tokyo
The University of Tokyo
Yokoyama, Miyabishara
Japan, Tokyo
The University of Tokyo
Chiba, Mika
Japan, Tokyo
The University of Tokyo
Motozono, Chihiro
Japan, Kumamoto
Kumamoto University
Nasser, Hesham
Japan, Kumamoto
Kumamoto University
Shimizu, Ryo
Japan, Kumamoto
Kumamoto University
Kitazato, Kazuko
Japan, Kumamoto
Kumamoto University
Hasebe, Haruyo
Japan, Kumamoto
Kumamoto University
Nakagawa, So
Japan, Tokyo
Tokai University
Wu, Jiaqi
Japan, Tokyo
Tokai University
Takahashi, Miyoko
Japan, Tokyo
Tokai University
Fukuhara, Takasuke
Japan, Sapporo
Hokkaido University
Shimizu, Kenta
Japan, Sapporo
Hokkaido University
Tsushima, Kana
Japan, Sapporo
Hokkaido University
Kubo, Haruko
Japan, Sapporo
Hokkaido University
Kazuma, Yasuhiro
Japan, Kyoto
Kyoto University
Nomura, Ryosuke
Japan, Kyoto
Kyoto University
Horisawa, Yoshihito
Japan, Kyoto
Kyoto University
Nagata, Kayoko
Japan, Kyoto
Kyoto University
Kawai, Yugo
Japan, Kyoto
Kyoto University
Yanagida, Yohei
Japan, Kyoto
Kyoto University
Tashiro, Yusuke
Japan, Kyoto
Kyoto University
Tokunaga, Kenzo
Japan, Tokyo
National Institute of Infectious Diseases
Ozono, Seiya
Japan, Tokyo
National Institute of Infectious Diseases
Kawabata, Ryoko
Japan, Higashihiroshima
Hiroshima University
Morizako, Nanami
Japan, Miyazaki
University of Miyazaki
Sadamasu, Kenji
Japan, Tokyo
Tokyo Metropolitan Institute of Public Health
Asakura, Hiroyuki
Japan, Tokyo
Tokyo Metropolitan Institute of Public Health
Nagashima, Mami
Japan, Tokyo
Tokyo Metropolitan Institute of Public Health
Yoshimura, Kazuhisa
Japan, Tokyo
Tokyo Metropolitan Institute of Public Health
Trueba, Gabriel A.
Ecuador, Quito
Universidad San Francisco de Quito
Rojas-Silva, Patricio
Ecuador, Quito
Universidad San Francisco de Quito
Gutierrez, Bernardo M.
Ecuador, Quito
Universidad San Francisco de Quito
Bowen, John E.
United States, Seattle
University of Washington
Walls, Alexandra C.
United States, Seattle
University of Washington
United Kingdom, Cambridge
University of Cambridge
Jackson, Laurelle
South Africa, Durban
Africa Health Research Institute
Martin, Darren Patrick
South Africa, Cape Town
University of Cape Town
Smith, Kenneth G.C.
United Kingdom, Cambridge
University of Cambridge
Briggs, John A.G.
Germany, Planegg
Max-planck-institut Für Biochemie
Madissoon, Elo
United Kingdom, Hinxton
Wellcome Sanger Institute
United Kingdom, Hinxton
European Molecular Biology Laboratory
Meyer, Kerstin B.
United Kingdom, Hinxton
Wellcome Sanger Institute
Mlčochová, Petra
United Kingdom, Cambridge
University of Cambridge
Ceron-Gutierrez, Lourdes
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
Döffinger, Rainer
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
Teichmann, Sarah Amalia
United Kingdom, Hinxton
Wellcome Sanger Institute
United Kingdom, Cambridge
University of Cambridge
Fisher, Andrew J.
United Kingdom, Newcastle
Newcastle University
Pizzuto, Matteo Samuele
United States, San Francisco
Vir Biotechnology, Inc.
Corti, Davide
United States, San Francisco
Vir Biotechnology, Inc.
Hosmillo, Myra D.T.
United Kingdom, Cambridge
University of Cambridge
James, Leo C.
United Kingdom, Cambridge
The Medical Research Council Laboratory of Molecular Biology
Thukral, Lipi
India, New Delhi
Council of Scientific and Industrial Research India
Veesler, David
United States, Seattle
University of Washington
United States, Chevy Chase
Howard Hughes Medical Institute
Sigal, Alex
South Africa, Durban
Africa Health Research Institute
Germany, Berlin
Max Planck Institute for Infection Biology
South Africa, Durban
University of Kwazulu-natal
Goodfellow, Ian Gordon
United Kingdom, Cambridge
University of Cambridge
Sato, Kei
Japan, Tokyo
The University of Tokyo
Japan, Kawaguchi
Japan Science and Technology Agency
Gupta, Ravindra K.
United Kingdom, Cambridge
University of Cambridge
South Africa, Durban
Africa Health Research Institute
Statistics
Citations: 514
Authors: 122
Affiliations: 34
Identifiers
Doi:
10.1038/s41586-022-04474-x
ISSN:
00280836