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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Interfering with Host Proteases in SARS-CoV-2 Entry as a Promising Therapeutic Strategy

Author(s): Patrick Müller, Hannah Maus, Stefan Josef Hammerschmidt, Philip Maximilian Knaff, Volker Mailänder, Tanja Schirmeister and Christian Kersten*

Volume 29, Issue 4, 2022

Published on: 03 August, 2021

Page: [635 - 665] Pages: 31

DOI: 10.2174/0929867328666210526111318

Price: $65

Abstract

Due to its fast international spread and substantial mortality, the coronavirus disease COVID-19 evolved to a global threat. Since there is currently no causative drug against this viral infection available, science is striving for new drugs and other approaches to treat the new disease. Studies have shown that the cell entry of coronaviruses into host cells takes place through the binding of the viral spike (S) protein to cell receptors. Priming of the S protein occurs via hydrolysis by different host proteases. The inhibition of these proteases could impair the processing of the S protein, thereby affecting the interaction with the host-cell receptors and preventing virus cell entry. Hence, inhibition of these proteases could be a promising strategy for treatment against SARSCoV- 2. In this review, we discuss the current state of the art of developing inhibitors against the entry proteases furin, the transmembrane serine protease type-II (TMPRSS2), trypsin, and cathepsin L.

Keywords: SARS-CoV-2, COVID-19, host proteases, protease inhibitors, furin, cathepsin L, TMPRSS2, trypsin.

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