A Super-Resolution Spatial Atlas of SARS-CoV-2 Infection in Human Cells

Sep 2, 2025bioRxiv : the preprint server for biology

Detailed Map of SARS-CoV-2 Infection Inside Human Cells

AI simplified

Long Covid on OpenScience ↗PubMed ↗DOI ↗OA ↗

Abstract

A comprehensive super-resolution Atlas maps the localization of nearly all viral proteins and RNAs in human cells during SARS-CoV-2 infection.

The viral main protease, nsp5, is found within double-membrane vesicles, suggesting a reevaluation of replication organelle maturation.
Thin double-stranded RNA (dsRNA) connectors link double-membrane vesicles in the infection landscape.
Large, membrane-less dsRNA granules containing replicase components resemble viroplasms, indicating novel features of viral replication.
The antiviral drug nirmatrelvir leads to the formation of persistent bodies containing uncleaved polyproteins, potentially impacting viral replication.

AI simplified

The spatial organization of viral and host components dictates the course of infection, yet the nanoscale architecture of the SARS-CoV-2 life cycle remains largely uncharted. Here, we present a comprehensive super-resolution Atlas of SARS-CoV-2 infection, systematically mapping the localization of nearly all viral proteins and RNAs in human cells. This resource reveals that the viral main protease, nsp5, localizes to the interior of double-membrane vesicles (DMVs), challenging existing models and suggesting that polyprotein processing is a terminal step in replication organelle maturation. We identify previously undescribed features of the infection landscape, including thin dsRNA "connectors" that physically link DMVs, and large, membrane-less dsRNA granules decorated with replicase components, reminiscent of viroplasms. Finally, we show that the antiviral drug nirmatrelvir induces the formation of persistent, multi-layered bodies of uncleaved polyproteins. This spatial Atlas provides a foundational resource for understanding coronavirus biology and offers crucial insights into viral replication, assembly, and antiviral mechanisms.

Full Text

Full text is available at the source.

View full text ↗

Featured in

Long CovidIssue #2

Your muscles might be the key to understanding long COVID fatigue

↗

A Super-Resolution Spatial Atlas of SARS-CoV-2 Infection in Human Cells

Abstract

Full Text

Featured in

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the long covid brief