SARS-CoV-2 requires acidic pH to infect cells

Alex J.B. Kreutzberger, Anwesha Sanyal, Anand Saminathan, Louis Marie Bloyet, Spencer Stumpf, Zhuoming Liu, Ravi Ojha, Markku T. Patjas, Ahmed Geneid, Gustavo Scanavachi, Catherine A. Doyle, Elliott Somerville, Ricardo Bango Da Cunha Correia, Giuseppe Di Caprio, Sanna Toppila-Salmi, Antti Mäkitie, Volker Kiessling, Olli Vapalahti, Sean P.J. Whelan, Giuseppe BalistreriTom Kirchhausen

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry starts with membrane attachment and ends with spike (S) protein–catalyzed membrane fusion depending on two cleavage steps, namely, one usually by furin in producing cells and the second by TMPRSS2 on target cells. Endosomal cathepsins can carry out both. Using real-time three-dimensional single-virion tracking, we show that fusion and genome penetration require virion exposure to an acidic milieu of pH 6.2 to 6.8, even when furin and TMPRSS2 cleavages have occurred. We detect the sequential steps of S1-fragment dissociation, fusion, and content release from the cell surface in TMPRRS2-overexpressing cells only when exposed to acidic pH. We define a key role of an acidic environment for successful infection, found in endosomal compartments and at the surface of TMPRSS2-expressing cells in the acidic milieu of the nasal cavity.

Original languageEnglish
Article numbere2209514119
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number38
StatePublished - Sep 20 2022


  • 3D imaging
  • SARS-CoV-2
  • infection route
  • live-cell imaging
  • virus entry


Dive into the research topics of 'SARS-CoV-2 requires acidic pH to infect cells'. Together they form a unique fingerprint.

Cite this