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Comment
. 2022 Jul 23;7(1):251.
doi: 10.1038/s41392-022-01084-x.

TMPRSS2, a novel host-directed drug target against SARS-CoV-2

Christian Keller  1 , Eva Böttcher-Friebertshäuser  2 , Michael Lohoff  3
Affiliations
Comment

TMPRSS2, a novel host-directed drug target against SARS-CoV-2

Christian Keller et al. Signal Transduct Target Ther. .
No abstract available

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Inhibition of SARS-CoV-2 spike cleavage by TMPRSS2 inhibits virus entry. a Upper panel: Schematic representation of SARS-CoV-2 S cleavage by furin at the S1/S2 site and subsequent cleavage at the S2’ site by TMPRSS2. Cleavage at the S2’ site exposes the fusion peptide (FP), priming S for membrane fusion (cyan-colored S). Inhibition of TMPRSS2 by N-0385 (blue hexagon) causes incomplete cleavage of S (red-colored S). Lower panel: Complete cleavage of S supports membrane fusion and the release of the viral genome into the target cell. TMPRSS2 inhibition results in incomplete S cleavage and thus prevents fusion and virus entry. b Alignment of the amino acid sequences at the S1/S2 and S2‘ sites of different SARS-CoV-2 variants of concern, zoonotic SARS-CoV and MERS-CoV. Amino acid motifs highlighted in blue and orange are cleaved by furin and TMPRSS2, respectively. Motifs highlighted in pink are most likely cleaved by TMPRSS2. c Crystal structure of human TMPRSS2 (SRCR and serine protease domain) in complex with nafamostat (cyan, PDB: 7MEQ; upper left panel). Catalytic domain (cartoon style) of TMPRSS2 (upper right panel). The catalytic triad (green stick model) and nafamostat (cyan) are indicated. Structures of nafamostat (PubChem CID 4413) and N-0385 (PubChem CID 135169285, lower panels)
See this image and copyright information in PMC

Comment on

  • A TMPRSS2 inhibitor acts as a pan-SARS-CoV-2 prophylactic and therapeutic.
    Shapira T, Monreal IA, Dion SP, Buchholz DW, Imbiakha B, Olmstead AD, Jager M, Désilets A, Gao G, Martins M, Vandal T, Thompson CAH, Chin A, Rees WD, Steiner T, Nabi IR, Marsault E, Sahler J, Diel DG, Van de Walle GR, August A, Whittaker GR, Boudreault PL, Leduc R, Aguilar HC, Jean F. Shapira T, et al. Nature. 2022 May;605(7909):340-348. doi: 10.1038/s41586-022-04661-w. Epub 2022 Mar 28. Nature. 2022. PMID: 35344983 Free PMC article.

References

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