SARS-CoV-2 requires acidic pH to infect cells

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Abstract

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.

Article activity feed

  1. Andreas Herrmann

    Review 2: "SARS-CoV-2 requires acidic pH to infect cells"

    This paper investigates the role of acidic environments in cells for SARS-CoV-2 infection susceptibility using 3D single virion tracking microscopy. Reviewers find the study reliable but emphasize the need to validate the observations for the entry of authentic SARS-CoV-2 virus.

  2. Francisco Sobrino

    Review 1: ""SARS-CoV-2 requires acidic pH to infect cells"

    This paper investigates the role of acidic environments in cells for SARS-CoV-2 infection susceptibility using 3D single virion tracking microscopy. Reviewers find the study reliable but emphasize the need to validate the observations for the entry of authentic SARS-CoV-2 virus.