ArticleCell host & microbe2022
Mutations in SARS-CoV-2 variants of concern link to increased spike cleavage and virus transmission.
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Article in Cell host & microbe, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.
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120citing papers in PubMed
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Who cites it
120 citing papers in PubMed.
- Loss-of-function mutation in Omicron variants reduces spike protein expression and attenuates SARS-CoV-2 infection.Nature communications · 2026Article
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- Early Fc-effector antibody signatures impact COVID-19 disease trajectory.medRxiv : the preprint server for health sciences · 2026Article
- Antibody escape drives emergence of diverse spike haplotypes resembling variants of concern in persistent SARS-CoV-2 infections.Cell reports. Medicine · 2026Article
- Transcriptomic insights into the immune dynamics of wild-type mice challenged with SARS-CoV-2 Beta variant.Laboratory animal research · 2026Article
- Article
- Increased pathogenicity and transmission of SARS-CoV-2 Omicron XBB.1.9 subvariants, including HK.3 and EG.5.1, relative to BA.2.Journal of virology · 2025Article
- Whole-genome sequencing data from long-term serial passaging of 11 SARS-CoV-2 isolates.Microbiology resource announcements · 2025Article
- Molecular mechanisms of SARS-CoV-2 entry: implications for biomedical strategies.Microbiology and molecular biology reviews : MMBR · 2025Review
- Long-term serial passaging of SARS-CoV-2 reveals signatures of convergent evolution.Journal of virology · 2025Article
- SARS-CoV-2 ORF3a drives dynamic dense body formation for optimal viral infectivity.Nature communications · 2025Article
- Receptor Binding for the Entry Mechanisms of SARS-CoV-2: Insights from the Original Strain and Emerging Variants.Viruses · 2025Review
- The effect of molnupiravir and nirmatrelvir on SARS-CoV-2 genome diversity in severe models of COVID-19.Microbiology spectrum · 2025Article
- The consequences of SARS-CoV-2 within-host persistence.Nature reviews. Microbiology · 2025Review
- Replication differences of SARS-CoV-2 lineages may arise from unique RNA replication characteristics and nucleocapsid protein expression.Frontiers in cellular and infection microbiology · 2025Article
- Article
- In-silico development of a novel TLR2-mediating multi-epitope vaccine againstIn silico pharmacology · 2025Article
- Article
- The Clinical Anatomy of SARS-CoV-2 Variants of Concern in Central Greece During October 2020-July 2022.Microorganisms · 2024Article
- The impact of S2 mutations on Omicron SARS-CoV-2 cell surface expression and fusogenicity.Emerging microbes & infections · 2024Article
60 more citing papers are in PubMed but not listed here.
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Authors and funding
29 authors.
Alba EscaleraDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Ana S Gonzalez-ReicheDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Sadaf AslamDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Ignacio MenaDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Manon LaporteDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Rebecca L PearlDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Andrea FossatiQuantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94158, USA; QBI Coronavirus Research Group (QCRG), San Francisco, CA 94158, USA; J. David Gladstone Institutes, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158-2140, USA.
Raveen RathnasingheDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Hala AlshammaryDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Adriana van de GuchteDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Keith FarrugiaDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Yiren QinHuffington Center for Cell-based Research in Parkinson's Disease, Black Family Stem Cell Institute, Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10502, USA.
Mehdi BouhaddouQuantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94158, USA; QBI Coronavirus Research Group (QCRG), San Francisco, CA 94158, USA; J. David Gladstone Institutes, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158-2140, USA.
Thomas KehrerDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Lorena Zuliani-AlvarezQuantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94158, USA; QBI Coronavirus Research Group (QCRG), San Francisco, CA 94158, USA; J. David Gladstone Institutes, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158-2140, USA.
David A MeekinsDepartment of Diagnostic Medicine/Pathobiology and Center of Excellence for Emerging and Zoonotic Animal Diseases, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA.
Velmurugan BalaramanDepartment of Diagnostic Medicine/Pathobiology and Center of Excellence for Emerging and Zoonotic Animal Diseases, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA.
Chester McDowellDepartment of Diagnostic Medicine/Pathobiology and Center of Excellence for Emerging and Zoonotic Animal Diseases, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA.
Jürgen A RichtDepartment of Diagnostic Medicine/Pathobiology and Center of Excellence for Emerging and Zoonotic Animal Diseases, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA.
Goran BajicDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Emilia Mia SordilloDepartment of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Marion DejosezHuffington Center for Cell-based Research in Parkinson's Disease, Black Family Stem Cell Institute, Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10502, USA.
Thomas P ZwakaHuffington Center for Cell-based Research in Parkinson's Disease, Black Family Stem Cell Institute, Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10502, USA.
Nevan J KroganDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94158, USA; QBI Coronavirus Research Group (QCRG), San Francisco, CA 94158, USA; J. David Gladstone Institutes, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158-2140, USA.
Viviana SimonDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Randy A AlbrechtDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Harm van BakelDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Adolfo García-SastreDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: adolfo.garcia-sastre@mssm.edu.
Teresa AydilloDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: teresa.aydillo-gomez@mssm.edu.
Funding
NIAID Centers of Excellence for Influenza Research and Response: Universal Influenza Vaccine Research Activities75N93021C00014 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI GARCIA-SASTRE, ADOLFO · 2021 to 2025
$62.6MSARS-CoV adaptations through a Systems Biology Lens (SYBIL)U19AI135972 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Adolfo Garcia-Sastre · 2018 to 2026
$27.2MTechnology Development Project - Increasing the complexity of ex vivo human airway models for studying immune response to viral infectionU19AI142733 · NIAID · JACKSON LABORATORY · PI Adolfo Garcia-Sastre, Anna Karolina Palucka · 2019 to 2026
$23.1MRESEARCH PROJECT 2U19AI135990 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Nevan J Krogan · 2018 to 2026
$21.4MSex-specific effects of obestity on Influenza A virus infection and immunityP20GM130448 · NIGMS · KANSAS STATE UNIVERSITY · PI REVATHI GOVIND · 2020 to 2026
$15.8MVulnerability of SARS- CoV-2 Infection in Lung Cancer Based on Serological Antibody AnalysesU54CA260560 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI SHYR, YU · 2020 to 2024
$10.0MCOVID and Translational Science supercomputer (CATS)S10OD030463 · OD · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KOVATCH, PATRICIA · 2021 to 2021
$2.0MBig Omics Data Engine 2 SupercomputerS10OD026880 · OD · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KOVATCH, PATRICIA · 2019 to 2019
$2.0MNCI NIH HHS U54 CA260560NIAID NIH HHS 75N93021C00014NIAID NIH HHS HHSN272201400006CNIAID NIH HHS U19 AI135972NIAID NIH HHS U19 AI135990NIAID NIH HHS U19 AI142733NIGMS NIH HHS P20 GM130448NIH HHS S10 OD026880NIH HHS S10 OD030463
Abstract
SARS-CoV-2 lineages have diverged into highly prevalent variants termed "variants of concern" (VOCs). Here, we characterized emerging SARS-CoV-2 spike polymorphisms in vitro and in vivo to understand their impact on transmissibility and virus pathogenicity and fitness. We demonstrate that the substitution S:655Y, represented in the gamma and omicron VOCs, enhances viral replication and spike protein cleavage. The S:655Y substitution was transmitted more efficiently than its ancestor S:655H in the hamster infection model and was able to outcompete S:655H in the hamster model and in a human primary airway system. Finally, we analyzed a set of emerging SARS-CoV-2 variants to investigate how different sets of mutations may impact spike processing. All VOCs tested exhibited increased spike cleavage and fusogenic capacity. Taken together, our study demonstrates that the spike mutations present in VOCs that become epidemiologically prevalent in humans are linked to an increase in spike processing and virus transmission.
Indexed as
COVID-19SARS-CoV-2HumansMutationSpike Glycoprotein, CoronavirusSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2fusiongammaH655Y mutationomicronSARS-CoV-2spike cleavagesyncytia formationvariants of concern
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