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Updated: May 5, 2026

A Fluorogenic Peptide Cleavage Assay to Screen for Proteolytic Activity: Applications for coronavirus spike protein activation

A Fluorogenic Peptide Cleavage Assay to Screen for Proteolytic Activity: Applications for coronavirus spike protein activation

Published on: January 9, 2019

Spike destabilization attenuates Mink Cluster 5 SARS-CoV-2.

Julia N Faraone^1,2,3, Pei Li^1,2, Junping Hong^1,2

¹Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210.

Proceedings of the National Academy of Sciences of the United States of America

|March 3, 2026

Summary

This summary is machine-generated.

The mink cluster 5 (MC5V) variant of SARS-CoV-2 had an unstable spike protein, leading to reduced infectivity. This instability, driven by specific mutations, limited its spread and highlights the need for monitoring zoonotic viruses.

Keywords:

Mink SARS-CoV-2 fusion processing spike stability

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Published on: April 21, 2022

Area of Science:

Virology
Molecular Biology
Genetics

Background:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect various animal hosts, including mink.
A mink-associated variant, mink cluster 5 (MC5V), emerged in Denmark in early 2020.

Purpose of the Study:

To investigate the molecular mechanisms underlying the attenuated infectivity and spread of the MC5V variant.
To determine the role of spike protein mutations in MC5V fitness.

Main Methods:

Analysis of spike protein stability and processing.
Structural analysis of key mutations.
Assessment of viral infectivity and fusogenicity.

Main Results:

The MC5V spike protein exhibits intrinsic instability and impaired processing.
A single mutation, I692V in the S2 subunit, significantly contributes to these defects, along with Y453F in the receptor-binding domain.
Spike instability leads to spontaneous S1 shedding and reduced incorporation into virions, resulting in attenuated infectivity.

Conclusions:

Spike protein instability is a key factor limiting the fitness and zoonotic potential of SARS-CoV-2 variants like MC5V.
Continuous monitoring of zoonotic SARS-CoV-2 variants and emerging viral pathogens is crucial.