Cited by 413SARS-CoV-2 and COVID-19 ResearchCOVID-19 Clinical Research StudiesCOVID-19 epidemiological studies

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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

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Zhao, Hanjun, Lu, Lu, Peng, Zheng, Chen, Lin-Lei, Meng, Xinjin, Zhang, Chuyuan, Ip, Jonathan Daniel, Chan, Wan-Mui, Chu, Allen Wing-Ho, Chan, Kwok-Hung, Jin, Dong-Yan, Chen, Honglin, Yuen, Kwok-Yung, To, Kelvin Kai-Wang·2022·Emerging Microbes & Infections

DOI 10.1080/22221751.2021.2023329PMC PMC8774049

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Abstract

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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Figure 1. Viral replication in VeroE6/TMPRSS2, VeroE6 and Calu3 cells. (A) Viral replication kinetics in VeroE6/TMPRSS2 cells. (B) Viral replication kinetics in VeroE6 cells. (C) Viral replication kinetics in Calu3 cells. SARS-CoV-2 (0.1 TCID50 of Omicron or Delta variant) was inoculated to cells for viral infection. Cell culture supernatants were collected at indicated time points for RT-qPCR assay to determine viral RNA titres. Data are presented as mean ± SD from two independent experiments with four biological samples. * indicates P < 0.05, ** indicates P < 0.01 and *** indicates P < 0.001 when compared with Omicron variant.CC BY · PubMed Central

Figure 2. Delta variant outcompeted the replication of Omicron variant in VeroE6/TMPRSS2 and Calu3 cells. VeroE6/TMPRSS2, VeroE6, and Calu3 cells were co-infected by the Delta and Omicron variants with the Delta:Omicron ratio of 1:10, 1:1 and 10:1. Cell culture supernatants were collected at 24 hpi (A) and 48 hpi (B) for next-generation sequencing. The percentage of reads corresponding to the Delta and Omicron variant is determined for spike amino acid residues 222 (Omicron: A; Delta: V), 655 (Omicron: Y; Delta H), and 950 (Omicron: D, Delta: N). * indicates P < 0.05, ** indicates P < 0.01 and *** indicates P < 0.001.CC BY · PubMed Central

Figure 3. Camostat could not potently inhibit the replication of Omicron variant in VeroE6/TMPRSS2 cells. (A) Bafilomycin A1 inhibited the Omicron and Delta replication in VeroE6/TMPRSS2 cells. (B) Chloroquine inhibited the Omicron and Delta replication in VeroE6/TMPRSS2 cells. (C) Camostat could potently inhibit Delta variant but not Omicron variant replication in VeroE6/TMPRSS2 cells. Cells were pretreated by the indicated bafilomycin A1, chloroquine or camostat before viral infection, 1000 TCID50 of virus was added to cells for infection and then viral RNA copies in cell lysate were measured at 8 hpi by RT-qPCR. Viral RNA (%) was normalized to the viral RNA copy of untreated virus. ** indicates P < 0.01 and *** indicates P < 0.001 when compared with untreated virus. Data are presented as mean ± SD from three independent biological samples.CC BY · PubMed Central

Figure 4. SARS-CoV-2 mediated cell-cell fusion. (A) Cell GFP images of infected cells at indicated post infection time. (B) Bright field images of infected cells at indicated post infection time. VeroE6/TMPRSS2 cells were transfected with GFP plasmid and infected with 0.1 TCID50 virus (Omicron and Delta variant). Images were taken at 24, 48, and 72 hpi. GFP-transfected cells without viral infection were the negative control of cell fusion (no infection). Scale bar = 50 μm. Experiment images were taken from two independent biological samples.CC BY · PubMed Central

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Background
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Influential
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Self-citation
Recent insights into SARS‐CoV‐2 omicron variant
da Silva, S. J. R., Kohl, A., Pena, L., & Pardee, K. (2022) · Reviews in Medical Virology · doi:10.1002/rmv.2373 · Cited by 56
“viral replication of the omicron variant and compared it with the delta variant.(22) This work showed that the omicron variant replicated more slowly than the delta variant in transmembrane serine protease 2 (TMPRSS2)‐overexpressing VeroE6 (VeroE6/TMPRSS2) cells, which provides an interesting way to evaluate the pathw…”
BackgroundResult
Limited cross-variant immunity after infection with the SARS-CoV-2 Omicron variant without vaccinationPreprint
Suryawanshi, R., Chen, I. P., Ma, T., Syed, A. M., Simoneau, C., Ciling, A., Khalid, M., Sreekumar, B., Chen, P.-Y., George, A. F., et al. (2022) · medRxiv · doi:10.1101/2022.01.13.22269243 · Cited by 45
Molecular insights into the adaptive evolution of SARS-CoV-2 spike protein
Yao, Z., Zhang, L., Duan, Y., Tang, X., & Lü, J. (2024) · Journal of Infection · doi:10.1016/j.jinf.2024.106121 · Cited by 49
The SARS‐CoV‐2 Omicron (B.1.1.529) variant and effectiveness of existing vaccines: What we know so far
Sohan, M., Hossain, M. J., & Islam, M. R. (2022) · Journal of Medical Virology · doi:10.1002/jmv.27574 · Cited by 44
“November 2021, has prompted worldwide fear due to its contagiousness and immunity escaping capacity.(1,2) Omicron has gotten a”
Background
Literature Review of Omicron: A Grim Reality Amidst COVID-19
Arora, S., Grover, V., Saluja, P., Algarni, Y. A., Saquib, S. A., Asif, S. M., Batra, K., Alshahrani, M. Y., Das, G., Jain, R., et al. (2022) · Microorganisms · doi:10.3390/microorganisms10020451 · Cited by 56
“Recent studies have reported that Omicron has a different mechanism for entering the host, and is capable of gaining cell entry independent of the transmembrane serine protease 2 (TMPRSS2) [24].”
Background
Is Booster Dose Strategy Sufficient for Omicron Variant of SARS-CoV-2?
Chavda, V. P., & Apostolopoulos, V. (2022) · Vaccines · doi:10.3390/vaccines10030367 · Cited by 50
“As such, the Spike protein is used in most currently approved vaccines, however, significant concerns about Omicron’s enhanced transmissibility and immune escape have been raised [13].”
Background
SARS‐CoV‐2 Omicron and its current known unknowns: A narrative review
Le, T. T. B., Vasanthakumaran, T., Hau, N. T. H., Hung, I., Luu, M. N., Khan, Z. A., An, N. T., Tran, V. P., Lee, W. J., Aziz, J. M. A., et al. (2022) · Reviews in Medical Virology · doi:10.1002/rmv.2398 · Cited by 42
A Quick Displacement of the SARS-CoV-2 variant Delta with Omicron: Unprecedented Spike in COVID-19 Cases Associated with Fewer Admissions and Comparable Upper Respiratory Viral Loads
Fall, A., Eldesouki, R., Sachithanandham, J., Morris, C., Norton, J., Gaston, D. C., Forman, M., Abdullah, O., Gallagher, N., Li, M., et al. (2022) · medRxiv · doi:10.1101/2022.01.26.22269927 · Cited by 39
“The slower viral growth might indicate an 302 alternative entry pathway that is less dependent on TMPRSS2 (27).”
Influential
Omicron subvariant BA.5 efficiently infects lung cells
Hoffmann, M., Wong, L.-Y. R., Arora, P., Zhang, L., Rocha, C., Odle, A. E., Nehlmeier, I., Kempf, A. M., Richter, A. M., Halwe, N. J., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-39147-4 · Cited by 38
COVID-19 disease severity in US Veterans infected during Omicron and Delta variant predominant periods
Mayr, F., Talisa, V. B., Castro, A. D., Shaikh, O. S., Omer, S. B., & Butt, A. A. (2022) · Nature Communications · doi:10.1038/s41467-022-31402-4 · Cited by 51
Evolution of nasal and olfactory infection characteristics of SARS-CoV-2 variants
Chen, M., Pekosz, A. S., Villano, J., Shen, W., Zhou, R., Kulaga, H. M., Li, Z., Smith, A. K., Gurung, A., Beck, S. E., et al. (2024) · Journal of Clinical Investigation · doi:10.1172/jci174439 · Cited by 52
“The decreased olfactory tropism in the Omicron variant is consistent with the recently reported endocytic entry pathway (26, 27).”
SARS-CoV-2 Omicron spike H655Y mutation is responsible for enhancement of the endosomal entry pathway and reduction of cell surface entry pathways
Yamamoto, M., Tomita, K., Hirayama, Y., Inoue, J.-I., Kawaguchi, Y., & Gohda, J. (2022) · doi:10.1101/2022.03.21.485084 · Cited by 36
“Omicron variant displays poor syncytium formation mediated by metalloproteinases without affecting the S1/S2 cleavage of its S protein Reduced syncytia formation through the TMPRSS2 pathway has been reported in Omicron, suggesting a correlation with lower pathogenicity [2, 10, 12, 13].”
Influential
Influence of immune escape and nasopharyngeal virus load on the spread of SARS-CoV-2 Omicron variant
Migueres, M., Diméglio, C., Trémeaux, P., Abravanel, F., Raymond, S., Lhomme, S., Mansuy, J., & Izopet, J. (2022) · Journal of Infection · doi:10.1016/j.jinf.2022.01.036 · Cited by 36
Functional properties of the spike glycoprotein of the emerging SARS-CoV-2 variant B.1.1.529
Wang, Q., Anang, S., Iketani, S., Guo, Y., Liu, L., Katsamba, P. S., Shapiro, L. S., Ho, D. D., & Sodroski, J. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110924 · Cited by 34
“529 S glycoprotein predominantly occurs through the use of endosomal cathepsins, consistent with other reports (Meng et al., 2022; Zhao et al., 2022).”
Hydroxychloroquine blocks SARS-CoV-2 entry into the endocytic pathway in mammalian cell culture
Yuan, Z., Pavel, M. A., Wang, H., Kwachukwu, J. C., Mediouni, S., Jablonski, J. A., Nettles, K. W., Reddy, C. B., Valente, S. T., & Hansen, S. B. (2022) · Communications Biology · doi:10.1038/s42003-022-03841-8 · Cited by 69
Covid-19: is omicron less lethal than delta?
Lorenzo-Redondo, R., Ozer, E. A., & Hultquist, J. F. (2022) · BMJ · doi:10.1136/bmj.o1806 · Cited by 36
SARS-CoV-2 Variants of Concern Hijack IFITM2 for Efficient Replication in Human Lung Cells
Nchioua, R., Schundner, A., Kmieć, D., Bozzo, C. P., Zech, F., Koepke, L., Graf, A., Krebs, S., Blum, H., Frick, M., et al. (2022) · Journal of Virology · doi:10.1128/jvi.00594-22 · Cited by 38
Antiviral Molecular Targets of Essential Oils against SARS-CoV-2: A Systematic Review
Iqhrammullah, M., Rizki, D., Purnama, A., Duta, T. F., Harapan, H., Idroes, R., & Ginting, B. (2023) · Scientia Pharmaceutica · doi:10.3390/scipharm91010015 · Cited by 33
“replication and fusion activities in TMPRSS2-expressing cells, such as in Omicron; the activities are lower compared to the Delta variant [60].”
Background
SARS-CoV-2 and influenza co-infection: A cross-sectional study in central Missouri during the 2021–2022 influenza season
Tang, C. Y., Boftsi, M., Staudt, L., McElroy, J. A., Li, T., Duong, S., Ohler, A., Ritter, D. G., Hammer, R., Hang, J., et al. (2022) · Virology · doi:10.1016/j.virol.2022.09.009 · Cited by 34
Revealing the mystery of persistent smell loss in long COVID patients
Park, J. W., Wang, X., & Xu, R. (2022) · International Journal of Biological Sciences · doi:10.7150/ijbs.73485 · Cited by 38
“Early estimation indicates that Omicron is less severe than the previous variants, possibly due to its less efficient viral replication [5, 6].”
Background
Passive Immunotherapy Against SARS-CoV-2: From Plasma-Based Therapy to Single Potent Antibodies in the Race to Stay Ahead of the Variants
Strohl, W. R., Ku, Z., An, Z., Carroll, S. F., Keyt, B. A., & Strohl, L. M. (2022) · BioDrugs · doi:10.1007/s40259-022-00529-7 · Cited by 35
Association of Infection with Different SARS-CoV-2 Variants during Pregnancy with Maternal and Perinatal Outcomes: A Systematic Review and Meta-Analysis
Deng, J., Ma, Y., Liu, Q., Du, M., Liu, M., & Liu, J. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph192315932 · Cited by 37
“In vitro experiments have also shown that Omicron has lower replication and fusion activity than Delta [42].”
Background
Antigenic evolution of SARS coronavirus 2
Mykytyn, A. Z., Fouchier, R. A. M., & Haagmans, B. L. (2023) · Current Opinion in Virology · doi:10.1016/j.coviro.2023.101349 · Cited by 36
Nanoparticle Delivery Platforms for RNAi Therapeutics Targeting COVID-19 Disease in the Respiratory Tract
Zhang, Y., Almazi, J. G., Ong, H. X., Johansen, M. D., Ledger, S., Traini, D., Hansbro, P. M., Kelleher, A. D., & Ahlenstiel, C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23052408 · Cited by 32
“Particularly, Paxlovid might have therapeutic potential in the newly emerging Omicron variant [10], which is fundamentally different from previous VOC, as it does not appear to use the TMPRSS2 protease co-receptor [11,12] or target the lung as effectively as previous ones [13–17].”
Background
Spike protein-independent attenuation of SARS-CoV-2 Omicron variant in laboratory mice
Liu, S., Selvaraj, P., Sangare, K., Luan, B., & Wang, T. T. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111359 · Cited by 29
“In support, the Omicron spike is less fusogenic compared with that of the Delta variant (Cong Zeng et al., 2021; Zhao et al., 2021).”
PCIF1-mediated deposition of 5′-cap N 6 ,2′- O -dimethyladenosine in ACE2 and TMPRSS2 mRNA regulates susceptibility to SARS-CoV-2 infection
Wang, L., Wang, S., Wu, L., Li, W., Bray, W. A., Clark, A. E., Gonzalez, G. M., Wang, Y., Carlin, A. F., & Rana, T. M. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2210361120 · Cited by 35
“Interestingly, a possible explanation for the latter observation comes from two recent studies suggesting that Omicron is less dependent than other SARS-CoV-2 strains on TMPRSS2 for cell infection (27, 28).”
Result
SARS-CoV-2 variants: Impact on biological and clinical outcome
Mahilkar, S., Agrawal, S. R., Chaudhary, S., Parikh, S., Sonkar, S. C., Verma, D. K., Chitalia, V., Mehta, D., Koner, B. C., Vijay, N., et al. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2022.995960 · Cited by 36
“The difference in entry pathways between the Omicron and Delta variants may have an implication on the clinical manifestations or disease severity (95).”
Background
Ancestral SARS-CoV-2, but not Omicron, replicates less efficiently in primary pediatric nasal epithelial cells
Zhu, Y., Chew, K. Y., Wu, M., Karawita, A. C., McCallum, G., Steele, L. E., Yamamoto, A., Labzin, L. I., Yarlagadda, T., Khromykh, A. A., et al. (2022) · PLoS Biology · doi:10.1371/journal.pbio.3001728 · Cited by 41
“These data support suggestions that Omicron does not necessarily have a replicative advantage over Delta in the URT of adults [33], and the observed increase in transmission with Omicron in adults is more likely reflective of increased antibody evasion [34–37].”
Computational studies on the interaction of SARS-CoV-2 Omicron SGp RBD with human receptor ACE2, limonin and glycyrrhizic acid
Vardhan, S., & Sahoo, S. K. (2022) · Comput. Biol. Medicine · doi:10.1016/j.compbiomed.2022.105367 · Cited by 30
SARS-CoV-2 omicron BA.5 and XBB variants have increased neurotropic potential over BA.1 in K18-hACE2 mice and human brain organoids
Stewart, R., Yan, K., Ellis, S. A., Bishop, C. R., Dumenil, T. D., Tang, B., Nguyen, W., Larcher, T., Parry, R. H., Sng, J. D. J., et al. (2023) · Frontiers in Microbiology · doi:10.3389/fmicb.2023.1320856 · Cited by 34
Endomembrane remodeling in SARS-CoV-2 infection
Chen, D., Zhao, Y. G., & Zhang, H. (2022) · Cell Insight · doi:10.1016/j.cellin.2022.100031 · Cited by 33
“The entry of Omicron mainly depends on the endocytic pathway, and compared to the Delta variant it thus exhibits lower infectivity in cells expressing high levels of TMPRSS2, and less sensitivity to the TMPRSS2 inhibitor Camostat (Meng et al., 2022; Zhao et al., 2022).”
Convergent Evolution Dynamics of SARS-CoV-2 and HIV Surface Envelope Glycoproteins Driven by Host Cell Surface Receptors and Lipid Rafts: Lessons for the Future
Fantini, J., Chahinian, H., & Yahi, N. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24031923 · Cited by 26
“infectio kinetics comparing the Delta and Omicron in Calu-3 cells, which have high level expressions of TMPRSS2 and in (TMPRSS2)-overexpressing VeroE6 cells [70].”
BackgroundInfluential
Potential of green tea EGCG in neutralizing SARS-CoV-2 Omicron variant with greater tropism toward the upper respiratory tract
Zhang, Z., Hao, M., Zhang, X., He, Y., Chen, X., Taylor, E. W., & Zhang, J. (2022) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2022.12.012 · Cited by 37
Comparison of clinical characteristics of wild-type SARS-CoV-2 and Omicron
Kırca, F., Aydoğan, S., Gözalan, A., Kayıpmaz, A., Özdemir, F. A. E., Tekçe, Y., Beşer, İ. O., Gun, P., Ökten, R. S., & Dinç, B. (2022) · Revista da Associação Médica Brasileira · doi:10.1590/1806-9282.20220880 · Cited by 26
Alterations in SARS-CoV-2 Omicron and Delta peptides presentation by HLA molecules
Nersisyan, S. A., Zhiyanov, A., Zakharova, M., Ishina, I. A., Kurbatskaia, I. N., Mamedov, A. E., Galatenko, A. V., Shkurnikov, M. Y., Gabibov, A. G., & Tonevitsky, A. (2022) · PeerJ · doi:10.7717/peerj.13354 · Cited by 28
The SARS-CoV-2 Omicron (B.1.1.529) variant exhibits altered pathogenicity, transmissibility, and fitness in the golden Syrian hamster modelPreprint
Yuan, S.-F., Ye, Z.-W., Liang, R., Tang, K., Zhang, A., Lu, G., Ong, C., Poon, V., Chan, C., Mok, B.-B. W., et al. (2022) · bioRxiv · doi:10.1101/2022.01.12.476031 · Cited by 26
“In human lung-derived Calu-3 cells, the Omicron variant shows 200 lower replication than the Delta variant and D614G strain in in pseudovirus and/or live virus 201 assays (21,27).”
BackgroundSelf-citation
Alpha-1-antitrypsin and its variant-dependent role in COVID-19 pathogenesisPreprint
Stevens, C. S., Oguntuyo, K. Y., Kowdle, S., Brambilla, L., Haas, G. D., Gowlikar, A., Siddiquey, M. N. A., Schilke, R. M., Woolard, M. D., Zhang, H., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.08.14.248880 · Cited by 33
“While many similarities exist between all variants of concern (VOCs), some 247 show distinct differences, particularly in viral entry and proteolytic processing of Spike 248 (4, 22, 25).”
SARS-CoV-2 Omicron (B.1.1.529) Variant: A Challenge with COVID-19
Afshar, Z. M., Pirzaman, A. T., Karim, B., Anaraki, S. R., Hosseinzadeh, R., Pireivatlou, E. S., Babazadeh, A., Hosseinzadeh, D., Miri, S. R., Sio, T. T. W., et al. (2023) · Diagnostics · doi:10.3390/diagnostics13030559 · Cited by 29
Performance of nasopharyngeal swab and saliva in detecting Delta and Omicron SARS‐CoV‐2 variants
Uršič, T., Kogoj, R., Šikonja, J., Roškarič, D., Virant, M. J., Bogovič, P., & Petrovec, M. (2022) · Journal of Medical Virology · doi:10.1002/jmv.27898 · Cited by 25
“These findings could also be explained by evidence of less efficient replication and fusion activity of Omicron when compared with Delta variant in TMPRSS2‐expressed cells, which could be the reason for less severe lung pathology.(26,31) Although the results between NPS and saliva in the Delta wave were highly concord…”
Result
Therapeutics to Tackle Omicron Outbreak
Chavda, V. P., Ghali, E. N. H. K., Yallapu, M. M., & Apostolopoulos, V. (2022) · Immunotherapy · doi:10.2217/imt-2022-0064 · Cited by 31
“The viral replication of the Omicron variant is through an endocytic pathway rather than the transmembrane serine protease 2 pathway as that of other variants of concern [22].”
Background
Sub‐lineages of the SARS‐CoV‐2 Omicron variants: Characteristics and prevention
Xu, A., Hong, B., Lou, F., Wang, S., Li, W., Shafqat, A., An, X., Zhao, Y., Song, L., Tong, Y., et al. (2022) · MedComm · doi:10.1002/mco2.172 · Cited by 30
Fusion-inhibition peptide broadly inhibits influenza virus and SARS-CoV-2, including Delta and Omicron variants
Zhao, H., Meng, X., Peng, Z., Lam, H., Zhang, C., Zhou, X., Chan, J. F., Kao, R. Y. T., To, K. K., & Yuen, K. (2022) · Emerging Microbes & Infections · doi:10.1080/22221751.2022.2051753 · Cited by 26
“not on TMPRSS2 for viral replication [30].”
Self-citation
FIFA World Cup 2022: What can we learn from the inspiring Tokyo 2020 Olympic Games held in COVID-19 times?
Dergaa, I., Musa, S., Romdhani, M., Souissi, A., Abdulmalik, M., Chamari, K., & Saad, H. B. (2022) · Biology of Sport · doi:10.5114/biolsport.2022.113293 · Cited by 24
“If we take the example of the Omicron strain, the virus evolved in a way that it became highly contagious and less severe compared to previous variants [33].”
Result
Phenotypic evolution of SARS-CoV-2 spike during the COVID-19 pandemic
Furnon, W., Cowton, V. M., Lorenzo, G. D., Orton, R. J., Herder, V., Cantoni, D. M., Ilia, G., Mendonça, D. C., Kerr, K., Allan, J., et al. (2025) · Nature Microbiology · doi:10.1038/s41564-024-01878-5 · Cited by 23
Interferon‐inducible phospholipids govern IFITM3‐dependent endosomal antiviral immunity
Unali, G., Crivicich, G., Pagani, I., Alezz, M. A., Folchini, F., Valeri, E., Matafora, V., Reisz, J. A., Giordano, A. M. S., Cuccovillo, I., et al. (2023) · The EMBO Journal · doi:10.15252/embj.2022112234 · Cited by 26
“In agreement with a recently proposed endosomal entry mechanism for the recent SARS-CoV2 Omicron variant (Pia & Rowland-Jones, 2022; Zhao et al, 2022), Omicron Spike-gp-pseudotyped LV were susceptible to both IFITM1 and IFITM3 in Calu3 cells (Fig 7G), and replicating SARS-CoV2 Omicron was mostly…”
Background
A Glycosylated RBD Protein Induces Enhanced Neutralizing Antibodies against Omicron and Other Variants with Improved Protection against SARS-CoV-2 Infection
Shi, J., Zheng, J. H., Tai, W., Verma, A. K., Zhang, X., Geng, Q., Wang, G., Guan, X., Malisheni, M. M., Odle, A. E., et al. (2022) · Journal of Virology · doi:10.1128/jvi.00118-22 · Cited by 24
Characteristics of the SARS-CoV-2 Omicron (B.1.1.529) Variant and Emerging Impact on Global Public Health
Islam, M. R., Nasreen, W., Anjum, R., Shahriar, M., Roy, A., Dhama, K., & Bhuiyan, M. A. (2022) · Clinical Pathology · doi:10.1177/2632010x221124908 · Cited by 22
Marine natural products and human immunity: novel biomedical resources for anti-infection of SARS-CoV-2 and related cardiovascular disease
Hu, C. (2024) · Natural Products and Bioprospecting · doi:10.1007/s13659-024-00432-4 · Cited by 24
“…[152], a combination of BRII-196/ BRII-198 [153], as well as healthy E(e)SEEDi lifestyle [70, 71] and better nutrient strategies [154–158], will help to combat the infection of SARS-CoV-2 and its major variants (Delta, Omicron, and XBB) [159–161], thus, combat finally the COVID-19 infection.”
Background
Comparison of the characteristics, morbidity and mortality of COVID-19 between first and second/third wave in a hospital setting in Lombardy: a retrospective cohort study
Leidi, F., Boari, G., Scarano, O., Mangili, B., Gorla, G., Corbani, A., Accordini, B., Napoli, F., Ghidelli, C., Archenti, G., et al. (2022) · Internal and Emergency Medicine · doi:10.1007/s11739-022-03034-5 · Cited by 21
“Therefore, such an impressive decrease in mortality in a non-vaccinated population may be fully explained not only by the factors reported above (i.e. early diagnosis and hospitalization and improvement of the hospital treatment and care) but maybe also by a progressive reduction of SARS-CoV-2 lethality, in line with…”
Omicron BA.2 Lineage, the “Stealth” Variant: Is It Truly a Silent Epidemic? A Literature Review
Tiecco, G., Storti, S., Arsuffi, S., Degli-Antoni, M., Focà, E., Castelli, F., & Quiros-Roldan, E. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23137315 · Cited by 21
“However, in vitro entry assay studies state that Omicron variant infection is not enhanced by TMPRSS2, and no particular difference has been seen between Delta and Omicron entry that might explain the overtake of Delta by Omicron [35].”
Background
Sequential glycosylations at the multibasic cleavage site of SARS-CoV-2 spike protein regulate viral activity
Wang, S., Ran, W., Sun, L., Fan, Q., Zhao, Y., Wang, B., Yang, J., He, Y., Wu, Y. T., Wang, Y., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-48503-x · Cited by 22
Self-citation
In silico analysis of mutations near S1/S2 cleavage site in SARS‐CoV‐2 spike protein reveals increased propensity of glycosylation in Omicron strain
Beaudoin, C. A., Pandurangan, A. P., Kim, S. Y., Hamaia, S. W., Huang, C. L.-H., Blundell, T. L., Vedithi, S. C., & Jackson, A. P. (2022) · Journal of Medical Virology · doi:10.1002/jmv.27845 · Cited by 19
Intra- vs. Interhost Evolution of SARS-CoV-2 Driven by Uncorrelated Selection—The Evolution Thwarted
Hou, M., Shi, J., Gong, Z., Wen, H., Lan, Y., Deng, X., Fan, Q., Li, J. J., Jiang, M., Tang, X., et al. (2023) · Molecular Biology and Evolution · doi:10.1093/molbev/msad204 · Cited by 35
“Also, Omicron is more infectious than Delta but has a lower viral load than Delta (Puhach et al. 2022), even in rhesus macaque (van Doremalen et al. 2022).”
BackgroundInfluential
LC-MS/MS: A sensitive and selective analytical technique to detect COVID-19 protein biomarkers in the early disease stage
Gajula, S. N. R., Khairnar, A. S., Jock, P., Kumari, N., Pratima, K., Munjal, V., Kalan, P., & Sonti, R. (2023) · Expert Review of Proteomics · doi:10.1080/14789450.2023.2191845 · Cited by 23
“mainland China to achieve their Zero Covid strategy [4].”
Background
A trifunctional peptide broadly inhibits SARS-CoV-2 Delta and Omicron variants in hamsters
Zhao, H.-J., To, K., Lam, H.-Y., Zhang, C., Peng, Z., Meng, X.-J., Wang, X.-K., Zhang, A., Yan, B., Cai, J.-P., et al. (2022) · Cell Discovery · doi:10.1038/s41421-022-00428-9 · Cited by 19
Self-citation

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: Zhao, Hanjun
Chen, Lin-Lei
Ip, Jonathan Daniel
Chan, Wan-Mui
Chu, Allen Wing-Ho
Chan, Kwok-Hung
Jin, Dong-Yan
Chen, Honglin
Yuen, Kwok-Yung
To, Kelvin Kai-Wang
Venue: Emerging Microbes & Infections
Publisher: Informa UK Limited
Published: 2022-01-19
Volume: 11
Issue: 1
Pages: 277-283
ISSN: 2222-1751 (ISSN-L)
DOI: 10.1080/22221751.2021.2023329
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: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
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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SARS-CoV-2 Omicron variant shows less efficient replication and fusion activity when compared with Delta variant in TMPRSS2-expressed cells

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