TMPRSS2 Protease Inhibitors May Prolong But Heparins Accelerate SARS-CoV-2 Clearance

Shu Yuan; Si-Cong Jiang; Zhong-Wei Zhang; Zi-Lin Li; Chang-Quan Wang; Ming Yuan; Yang-Er Chen; Qi Tao; Ting Lan; Xiao-Yan Tang; Guang-Deng Chen; Jian Zeng

doi:10.20944/preprints202006.0249.v1

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preprints.org > biology and life sciences > immunology and microbiology > doi: 10.20944/preprints202006.0249.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

TMPRSS2 Protease Inhibitors May Prolong But Heparins Accelerate SARS-CoV-2 Clearance

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Version 1 : Received: 20 June 2020 / Approved: 21 June 2020 / Online: 21 June 2020 (10:12:34 CEST)

How to cite: Yuan, S.; Jiang, S.; Zhang, Z.; Li, Z.; Wang, C.; Yuan, M.; Chen, Y.; Tao, Q.; Lan, T.; Tang, X.; Chen, G.; Zeng, J. TMPRSS2 Protease Inhibitors May Prolong But Heparins Accelerate SARS-CoV-2 Clearance. Preprints 2020, 2020060249. https://doi.org/10.20944/preprints202006.0249.v1 Yuan, S.; Jiang, S.; Zhang, Z.; Li, Z.; Wang, C.; Yuan, M.; Chen, Y.; Tao, Q.; Lan, T.; Tang, X.; Chen, G.; Zeng, J. TMPRSS2 Protease Inhibitors May Prolong But Heparins Accelerate SARS-CoV-2 Clearance. Preprints 2020, 2020060249. https://doi.org/10.20944/preprints202006.0249.v1

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MDPI and ACS Style

Yuan, S.; Jiang, S.; Zhang, Z.; Li, Z.; Wang, C.; Yuan, M.; Chen, Y.; Tao, Q.; Lan, T.; Tang, X.; Chen, G.; Zeng, J. TMPRSS2 Protease Inhibitors May Prolong But Heparins Accelerate SARS-CoV-2 Clearance. Preprints 2020, 2020060249. https://doi.org/10.20944/preprints202006.0249.v1

APA Style

Yuan, S., Jiang, S., Zhang, Z., Li, Z., Wang, C., Yuan, M., Chen, Y., Tao, Q., Lan, T., Tang, X., Chen, G., & Zeng, J. (2020). TMPRSS2 Protease Inhibitors May Prolong But Heparins Accelerate SARS-CoV-2 Clearance. Preprints. https://doi.org/10.20944/preprints202006.0249.v1

Chicago/Turabian Style

Yuan, S., Guang-Deng Chen and Jian Zeng. 2020 "TMPRSS2 Protease Inhibitors May Prolong But Heparins Accelerate SARS-CoV-2 Clearance" Preprints. https://doi.org/10.20944/preprints202006.0249.v1

Abstract

The 2019 novel SARS-like coronavirus (SARS-CoV-2) entry depends on the host membrane serine protease TMPRSS2, which can be blocked by some clinically-proven drugs. Here we analyzed spatial relevance between glycosylation sequons and antibody epitopes and found that, different from SARS-CoV S, most high-surface-accessible epitopes of SARS-CoV-2 S are blocked by the glycosylation, and the optimal epitope with the highest surface accessibility is covered by the S1 cap. TMPRSS2 inhibitor treatments may prevent unmasking of this epitope and therefore prolong virus clearance and may induce antibody-dependent enhancement. Interestingly, a heparin-binding sequence immediately upstream of the S1/S2 cleavage site has been found in SARS-CoV-2 S but not in SARS-CoV S. Binding of SARS-CoV-2 with heparins may lead to exposure of S686, which then facilitates the S1/S2 cleavage, induces exposure of the optimal epitope, and therefore increases the antibody titres. A combination of heparin and vaccine (or convalescent serum) treatments thus is recommended.

Keywords

SARS-CoV-2; TMPRSS2; antibody epitopes; glycosylation sequons; heparin

Subject

Biology and Life Sciences, Immunology and Microbiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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