ArticlemBio2021
D614G Substitution of SARS-CoV-2 Spike Protein Increases Syncytium Formation and Virus Titer via Enhanced Furin-Mediated Spike Cleavage.
Article in mBio, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 44 citations in OpenAlex.
- Peste Des Petits Ruminants Virus Infection Induces Syncytium Formation via RhoA-Rock1 Signaling Pathway to Promote Viral Replication.Animals : an open access journal from MDPI · 2026Article
- SARS-CoV-2 membrane protein recruits PP2A to dephosphorylate the nucleocapsid and promote virion production.Journal of biomedical science · 2026Article
- Furin as a Novel Pan-Viral Therapeutic Target: Implications for Dengue and SARS-CoV-2.Viruses · 2026Review
- Article
- Tradeoffs between proliferation and transmission in virus evolution- insights from evolutionary and functional analyses of SARS-CoV-2.Virology journal · 2025Article
- Review
- Article
- SARS-CoV-2 Syncytium under the Radar: Molecular Insights of the Spike-Induced Syncytia and Potential Strategies to Limit SARS-CoV-2 Replication.Journal of clinical medicine · 2023Review
- SARS-CoV-2 omicron variants harbor spike protein mutations responsible for their attenuated fusogenic phenotype.Communications biology · 2023Article
- Ultrastructural study confirms the formation of single and heterotypic syncytial cells in bronchoalveolar fluids of COVID-19 patients.Virology journal · 2023Article
- Spike substitution T813S increases Sarbecovirus fusogenicity by enhancing the usage of TMPRSS2.PLoS pathogens · 2023Article
- Tight junction protein occludin is an internalization factor for SARS-CoV-2 infection and mediates virus cell-to-cell transmission.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- IFN-stimulated metabolite transporter ENT3 facilitates viral genome release.EMBO reports · 2023Article
- Structural evolution of Delta lineage of SARS-CoV-2.International journal of biological macromolecules · 2023Article
- Rural populations facilitated early SARS-CoV-2 evolution and transmission in Missouri, USA.Npj viruses · 2023Article
- Whole-Genome Comparison of Representatives of All Variants of SARS-CoV-2, Including Subvariant BA.2 and the GKA Clade.Advances in virology · 2023Article
- Estimation of virus-mediated cell fusion rate of SARS-CoV-2.Virology · 2022Article
- Adverse effects of COVID-19 mRNA vaccines: the spike hypothesis.Trends in molecular medicine · 2022Review
- Article
- Construction of SARS-CoV-2 spike-pseudotyped retroviral vector inducing syncytia formation.Virus genes · 2022Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Since the D614G substitution in the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged, the variant strain has undergone a rapid expansion to become the most abundant strain worldwide. Therefore, this substitution may provide an advantage for viral spreading. To explore the mechanism, we analyzed 18 viral isolates containing S proteins with either G614 or D614 (S-G614 and S-D614, respectively). The plaque assay showed a significantly higher virus titer in S-G614 than in S-D614 isolates. We further found increased cleavage of the S protein at the furin substrate site, a key event that promotes syncytium formation, in S-G614 isolates. The enhancement of the D614G substitution in the cleavage of the S protein and in syncytium formation has been validated in cells expressing S protein. The effect on the syncytium was abolished by furin inhibitor treatment and mutation of the furin cleavage site, suggesting its dependence on cleavage by furin. Our study pointed to the impact of the D614G substitution on syncytium formation through enhanced furin-mediated S cleavage, which might increase the transmissibility and infectivity of SARS-CoV-2 strains containing S-G614.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.