Inactivation of SARS-CoV-2 at acidic pH is driven by partial unfolding of spike
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...
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| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-08514-w |
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| author | Irina Glas Liv Zimmermann Beiping Luo Marie O. Pohl Antoni G. Wrobel Aline Schaub Liviana K. Klein Shannon C. David Elisabeth Gaggioli Nir Bluvshtein Michael Huber Athanasios Nenes Ulrich K. Krieger Thomas Peter Tamar Kohn Petr Chlanda Silke Stertz |
| author_facet | Irina Glas Liv Zimmermann Beiping Luo Marie O. Pohl Antoni G. Wrobel Aline Schaub Liviana K. Klein Shannon C. David Elisabeth Gaggioli Nir Bluvshtein Michael Huber Athanasios Nenes Ulrich K. Krieger Thomas Peter Tamar Kohn Petr Chlanda Silke Stertz |
| author_sort | Irina Glas |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ea8357b5754c49228e4bf98e749ba34c |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-ea8357b5754c49228e4bf98e749ba34c2025-08-20T04:03:06ZengNature PortfolioCommunications Biology2399-36422025-07-018111510.1038/s42003-025-08514-wInactivation of SARS-CoV-2 at acidic pH is driven by partial unfolding of spikeIrina Glas0Liv Zimmermann1Beiping Luo2Marie O. Pohl3Antoni G. Wrobel4Aline Schaub5Liviana K. Klein6Shannon C. David7Elisabeth Gaggioli8Nir Bluvshtein9Michael Huber10Athanasios Nenes11Ulrich K. Krieger12Thomas Peter13Tamar Kohn14Petr Chlanda15Silke Stertz16Institute of Medical Virology, University of ZurichSchaller Research Group, Department for Infectious Diseases, Virology, Heidelberg UniversityInstitute for Atmospheric and Climate Science, ETH ZurichInstitute of Medical Virology, University of ZurichDepartment of Biochemistry, University of OxfordEnvironmental Chemistry Laboratory, School of Architecture, Civil and Environmental Engineering, Swiss Federal Institute of Technology in LausanneInstitute for Atmospheric and Climate Science, ETH ZurichEnvironmental Chemistry Laboratory, School of Architecture, Civil and Environmental Engineering, Swiss Federal Institute of Technology in LausanneInstitute of Medical Virology, University of ZurichInstitute for Atmospheric and Climate Science, ETH ZurichInstitute of Medical Virology, University of ZurichLaboratory of Atmospheric Processes and their Impacts, School of Architecture, Civil and Environmental Engineering, Swiss Federal Institute of Technology in LausanneInstitute for Atmospheric and Climate Science, ETH ZurichInstitute for Atmospheric and Climate Science, ETH ZurichEnvironmental Chemistry Laboratory, School of Architecture, Civil and Environmental Engineering, Swiss Federal Institute of Technology in LausanneSchaller Research Group, Department for Infectious Diseases, Virology, Heidelberg UniversityInstitute of Medical Virology, University of ZurichAbstract 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.https://doi.org/10.1038/s42003-025-08514-w |
| spellingShingle | Irina Glas Liv Zimmermann Beiping Luo Marie O. Pohl Antoni G. Wrobel Aline Schaub Liviana K. Klein Shannon C. David Elisabeth Gaggioli Nir Bluvshtein Michael Huber Athanasios Nenes Ulrich K. Krieger Thomas Peter Tamar Kohn Petr Chlanda Silke Stertz Inactivation of SARS-CoV-2 at acidic pH is driven by partial unfolding of spike Communications Biology |
| title | Inactivation of SARS-CoV-2 at acidic pH is driven by partial unfolding of spike |
| title_full | Inactivation of SARS-CoV-2 at acidic pH is driven by partial unfolding of spike |
| title_fullStr | Inactivation of SARS-CoV-2 at acidic pH is driven by partial unfolding of spike |
| title_full_unstemmed | Inactivation of SARS-CoV-2 at acidic pH is driven by partial unfolding of spike |
| title_short | Inactivation of SARS-CoV-2 at acidic pH is driven by partial unfolding of spike |
| title_sort | inactivation of sars cov 2 at acidic ph is driven by partial unfolding of spike |
| url | https://doi.org/10.1038/s42003-025-08514-w |
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