Metalloproteinase-Dependent and TMPRSS2-Independent Cell Surface Entry Pathway of SARS-CoV-2 Requires the Furin Cleavage Site and the S2 Domain of Spike Protein

Author:

Yamamoto Mizuki1,Gohda Jin1,Kobayashi Ayako1,Tomita Keiko1,Hirayama Youko1,Koshikawa Naohiko2,Seiki Motoharu3,Semba Kentaro4,Akiyama Tetsu5,Kawaguchi Yasushi16ORCID,Inoue Jun-ichiro7ORCID

Affiliation:

1. Research Center for Asian Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

2. Department of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Japan

3. Division of Cancer Cell Research, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

4. Department of Life Science and Medical Bio-Science, Waseda University, Tokyo, Japan

5. Laboratory of Molecular and Genetic Information, Institute for Quantitative Biosciences, The University of Tokyo, Tokyo, Japan

6. Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

7. Research Platform Office, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

Abstract

To develop effective therapeutics against COVID-19, it is necessary to elucidate in detail the infection mechanism of the causative agent, SARS-CoV-2. SARS-CoV-2 binds to the cell surface receptor ACE2 via the spike protein, and then the spike protein is cleaved by host proteases to enable entry.

Funder

Ministry of Education, Culture, Sports, Science and Technology

MEXT | Japan Society for the Promotion of Science

Japan Agency for Medical Research and Development

University of Tokyo

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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