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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月21日

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  • 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

摘要

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.