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Commun Biol . Inactivation of SARS-CoV-2 at acidic pH is driven by partial unfolding of spike

tetano

Editor, Senior Moderator
Commun Biol


. 2025 Jul 21;8(1):1082.
doi: 10.1038/s42003-025-08514-w. Inactivation of SARS-CoV-2 at acidic pH is driven by partial unfolding of spike

Irina Glas[SUP] 1 [/SUP], Liv Zimmermann[SUP] 2 3 [/SUP], Beiping Luo[SUP] 4 [/SUP], Marie O Pohl[SUP] 1 [/SUP], Antoni G Wrobel[SUP] 5 [/SUP], Aline Schaub[SUP] 6 [/SUP], Liviana K Klein[SUP] 4 [/SUP], Shannon C David[SUP] 6 [/SUP], Elisabeth Gaggioli[SUP] 1 [/SUP], Nir Bluvshtein[SUP] 4 [/SUP], Michael Huber[SUP] 1 [/SUP], Athanasios Nenes[SUP] 7 8 [/SUP], Ulrich K Krieger[SUP] 4 [/SUP], Thomas Peter[SUP] 4 [/SUP], Tamar Kohn[SUP] 6 [/SUP], Petr Chlanda[SUP] 2 3 [/SUP], Silke Stertz[SUP] 9 [/SUP]



Affiliations
Abstract

SARS-CoV-2, the causative agent of COVID-19, is predominantly transmitted by respiratory aerosol and contaminated surfaces. Recent studies demonstrated that aerosols can become acidic, and acidification has been proposed as decontamination method. Here, we investigate how SARS-CoV-2 reacts to acidic pH and by which mechanism the virus is inactivated. We show that a pH below 3 is required to inactivate SARS-CoV-2 in a period of seconds to minutes. While we measured a 1000 to 10,000-fold drop in infectivity, virion structure remained intact under these conditions. Using super-resolution microscopy, we found that the attachment of virions to target cells is abrogated after acidic treatment, revealing spike protein (S) as the major inactivation target. Limited proteolysis of S combined with testing spike-specific antibodies for binding under low pH conditions revealed that exposure of SARS-CoV-2 to pH below 3 results in partial unfolding of S, thereby preventing binding of virions to target cells.


 
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