Cell Entry and Unusual Replication of SARS-CoV-2
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Updated: Aug 25, 2025

Production of a SARS-CoV-2 Virus-Like-Particle System to Investigate Viral Life Cycles In Vitro
Published on: June 6, 2025
Nathan McCann1, Francis J Castellino1
1Department of Chemistry and Biochemistry and W.M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, IN 46530, USA.
Background:
SARS-CoV-2 is the causative virus for the CoVID-19 pandemic that has frequently mutated to continue to infect and resist available vaccines. Emerging new variants of the virus have complicated notions of immunity conferred by vaccines versus immunity that results from infection. While we continue to progress from epidemic to endemic as a result of this collective immunity, the pandemic remains a morbid and mortal problem.
Objective:
The SARS-CoV-2 virus has a very complex manner of replication. The spike protein, one of the four structural proteins of the encapsulated virus, is central to the ability of the virus to penetrate cells to replicate. The objective of this review is to summarize these complex features of viral replication.
Methods:
A review of the recent literature was performed on the biology of SARS-CoV-2 infection from published work from PubMed and works reported to preprint servers, e.g., bioRxiv and medRxiv.
Results And Conclusion:
The complex molecular and cellular biology involved in SARS-CoV-2 replication and the origination of >30 proteins from a single open reading frame (ORF) have been summarized, as well as the structural biology of spike protein, a critical factor in the cellular entry of the virus, which is a necessary feature for it to replicate and cause disease.
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