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Role of proteolytic enzymes in the COVID-19 infection and promising therapeutic approaches.

Authors
  • Gioia, Magda1
  • Ciaccio, Chiara2
  • Calligari, Paolo3
  • De Simone, Giovanna4
  • Sbardella, Diego5
  • Tundo, Grazia5
  • Fasciglione, Giovanni Francesco6
  • Di Masi, Alessandra4
  • Di Pierro, Donato6
  • Bocedi, Alessio3
  • Ascenzi, Paolo7
  • Coletta, Massimo8
  • 1 Department of Clinical Sciences and Translational Medicine, University of Roma Tor Vergata, Roma, Italy. Electronic address: [email protected] , (Italy)
  • 2 Department of Clinical Sciences and Translational Medicine, University of Roma Tor Vergata, Roma, Italy. Electronic address: [email protected] , (Italy)
  • 3 Department of Chemical and Technological Sciences, University of Roma Tor Vergata, Roma, Italy. , (Italy)
  • 4 Department of Sciences, Roma Tre University, Roma, Italy. , (Italy)
  • 5 IRCCS-Fondazione Bietti, Rome, Italy. , (Italy)
  • 6 Department of Clinical Sciences and Translational Medicine, University of Roma Tor Vergata, Roma, Italy. , (Italy)
  • 7 Department of Sciences, Roma Tre University, Roma, Italy; Interdepartmental Laboratory for Electron Microscopy, Roma Tre University, Roma, Italy. , (Italy)
  • 8 Department of Clinical Sciences and Translational Medicine, University of Roma Tor Vergata, Roma, Italy. Electronic address: [email protected] , (Italy)
Type
Published Article
Journal
Biochemical pharmacology
Publisher
New York, NY : Elsevier Science Inc
Publication Date
Dec 01, 2020
Volume
182
Pages
114225–114225
Identifiers
DOI: 10.1016/j.bcp.2020.114225
PMID: 32956643
Source
Medline
Language
English
License
Unknown

Abstract

In the Fall of 2019 a sudden and dramatic outbreak of a pulmonary disease (Coronavirus Disease COVID-19), due to a new Coronavirus strain (i.e., SARS-CoV-2), emerged in the continental Chinese area of Wuhan and quickly diffused throughout the world, causing up to now several hundreds of thousand deaths. As for common viral infections, the crucial event for the viral life cycle is the entry of genetic material inside the host cell, realized by the spike protein of the virus through its binding to host receptors and its activation by host proteases; this is followed by translation of the viral RNA into a polyprotein, exploiting the host cell machinery. The production of individual mature viral proteins is pivotal for replication and release of new virions. Several proteolytic enzymes either of the host and of the virus act in a concerted fashion to regulate and coordinate specific steps of the viral replication and assembly, such as (i) the entry of the virus, (ii) the maturation of the polyprotein and (iii) the assembly of the secreted virions for further diffusion. Therefore, proteases involved in these three steps are important targets, envisaging that molecules which interfere with their activity are promising therapeutic compounds. In this review, we will survey what is known up to now on the role of specific proteolytic enzymes in these three steps and of most promising compounds designed to impair this vicious cycle. Copyright © 2020 Elsevier Inc. All rights reserved.

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