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SARS-CoV-2 Omicron variant shows less efficient replication and fusion activity when compared with Delta variant in TMPRSS2-expressed cells
Open accessAbstract
The novel SARS-CoV-2 Omicron variant (B.1.1.529), first found in early November 2021, has sparked considerable global concern and it has >50 mutations, many of which are known to affect transmissibility or cause immune escape. In this study, we sought to investigate the virological characteristics of the Omicron variant and compared it with the Delta variant which has dominated the world since mid-2021. Omicron variant replicated more slowly than the Delta variant in transmembrane serine protease 2 (TMPRSS2)-overexpressing VeroE6 (VeroE6/TMPRSS2) cells. Notably, the Delta variant replicated well in Calu3 cell line which has robust TMPRSS2 expression, while the Omicron variant replicated poorly in this cell line. Competition assay showed that Delta variant outcompeted Omicron variant in VeroE6/TMPRSS2 and Calu3 cells. To confirm the difference in entry pathway between the Omicron and Delta variants, we assessed the antiviral effect of bafilomycin A1, chloroquine (inhibiting endocytic pathway), and camostat (inhibiting TMPRSS2 pathway). Camostat potently inhibited the Delta variant but not the Omicron variant, while bafilomycin A1 and chloroquine could inhibit both Omicron and Delta variants. Moreover, the Omicron variant also showed weaker cell-cell fusion activity when compared with Delta variant in VeroE6/TMPRSS2 cells. Collectively, our results suggest that Omicron variant infection is not enhanced by TMPRSS2 but is largely mediated via the endocytic pathway. The difference in entry pathway between Omicron and Delta variants may have an implication on the clinical manifestations or disease severity.
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“suggesting entry selectivity of variants is associated with clinical manifestation [67].”
From Insights of Endocytosis Signaling in Health and Disease (2023) · cites this paper as [67]
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“Current evidence suggests that pharmacological inhibition of endocytic pathways potentially regressed replication of novel SARS-CoV-2 lineage B.1.1.529 (Omicron variant) in VeroE6/TMPRSS2 cell, suggesting entry selectivity of variants is associated with clinical manifestation [67].”
From Insights of Endocytosis Signaling in Health and Disease (2023) · cites this paper as [67]
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BackgroundSARS-CoV-2 pandemic: on its way to becoming an endemic disease?
Mattiuzzi, C., Henry, B., & Lippi, G. (2022) · doi:10.21203/rs.3.rs-1262987/v1
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ResultVariants of Coronavirus and Cardiovascular Diseases
Dara, M., Saffar, M., Dianatpour, M., Tanideh, N., Azarpira, N., & Talebzadeh, M. (2022) · Frontiers in Medical Case Reports · doi:10.47746/fmcr.2022.3602
Metadata
- Authors
- Zhao, H., Lu, L., Peng, Z., Chen, L.-L., Meng, X., Zhang, C., Ip, J. D., Chan, W.-M., Chu, A. W.-H., Chan, K.-H., Jin, D.-Y., Chen, H., Yuen, K.-Y., & To, K. K.-W.
- Affiliations
- University of Hong Kong (HK)
- Queen Mary Hospital (CN)
- Corresponding author
- Zhao, Hanjun
- To, Kelvin Kai-Wang
- ORCID
- Venue
- Emerging Microbes & Infections
- Publisher
- Informa UK Limited
- Published
- 2022-01-19
- Volume
- 11
- Issue
- 1
- Pages
- 277-283
- ISSN
- 2222-1751 (ISSN-L)
- PMC
- PMC8774049
- OpenAlex
- W4200625712
- Cited by
- 413
- References
- 25
- Citations by year
- 2026: 12 · 2025: 29 · 2024: 68 · 2023: 104 · 2022: 197
- FWCI
- 29.38
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Emerging Microbes & Infections (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Theme-Based Research Scheme (T11-709/21-N)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Physical Sciences › Mathematics › Modeling and Simulation › COVID-19 epidemiological studies
- Keywords
- Omicron variant, Delta variant, viral entry pathways, TMPRSS2, endocytic pathway, viral replication, cell-cell fusion, camostat, bafilomycin A1, chloroquine, competition assay
- MeSH terms
- Whole Genome Sequencing, COVID-19, SARS-CoV-2, Animals, Carcinoma, Non-Small-Cell Lung, Chlorocebus aethiops, Chloroquine, Endocytosis, Esters, Guanidines, Humans, Lung Neoplasms, Recombinant Proteins, Serine Endopeptidases, Vero Cells, Virus Cultivation, Virus Replication, Macrolides, Cell Line, Tumor, Virus Internalization, Immune Evasion
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