Cargando…

The old but new: Can unfractioned heparin and low molecular weight heparins inhibit proteolytic activation and cellular internalization of SARS-CoV2 by inhibition of host cell proteases?

Currently, our world is facing the 2019 Novel Coronavirus (COVID-19) outbreak and tremendous efforts are made for developing drugs to treat and vaccines to prevent the disease. At present, there is no specific antiviral drug or vaccine for COVID-19. The pathogenic infectivity of the virus requires t...

Descripción completa

Detalles Bibliográficos
Autores principales: Belen-Apak, F.B., Sarialioglu, F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Ltd. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169882/
https://www.ncbi.nlm.nih.gov/pubmed/32335456
http://dx.doi.org/10.1016/j.mehy.2020.109743
_version_ 1783523809792360448
author Belen-Apak, F.B.
Sarialioglu, F.
author_facet Belen-Apak, F.B.
Sarialioglu, F.
author_sort Belen-Apak, F.B.
collection PubMed
description Currently, our world is facing the 2019 Novel Coronavirus (COVID-19) outbreak and tremendous efforts are made for developing drugs to treat and vaccines to prevent the disease. At present, there is no specific antiviral drug or vaccine for COVID-19. The pathogenic infectivity of the virus requires the S1 subunit of the spike (S) protein to bind the host cell receptor, angiontensin converting enzyme (ACE2). While the binding to host cell receptor is the first step of infection, the entrance of the virus into the cell needs the cleavage of S1–S2 subunits to expose S2 for fusion to cell membrane via host proteases including cathepsins, cell surface transmembrane protease/serine (TMPRSS) proteases, furin, trypsin and factor Xa. Previous in vitro studies have shown that factor Xa inhibition can decrease viral infectivity. We suppose that host cell proteases including furin (as expressed highly in lungs), factor Xa and cathepsin are possible targets to decrease viral burden, therefore unfractioned heparin and low molecular weight heparin-LMWH (specifically dalteparin and tinzaparin for their anti inflammatory action) can be potential inhibitors of multiple endoproteases involved in virus infectivity. Our hypothesis needs to be tested in in vitro and clinical studies, however as we are in an urgent situation as the burden of SARS-CoV2 is increasing all around the world, we recommend the usage of unfractioned heparin or LMWH in intensive care unit (ICU) and non-ICU hospitalized patients with the risk–benefit judgement of the clinician. Whether our hypothesis is clinically applicable and successful in decreasing viral infection will be evaluated for further studies.
format Online
Article
Text
id pubmed-7169882
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Elsevier Ltd.
record_format MEDLINE/PubMed
spelling pubmed-71698822020-04-21 The old but new: Can unfractioned heparin and low molecular weight heparins inhibit proteolytic activation and cellular internalization of SARS-CoV2 by inhibition of host cell proteases? Belen-Apak, F.B. Sarialioglu, F. Med Hypotheses Article Currently, our world is facing the 2019 Novel Coronavirus (COVID-19) outbreak and tremendous efforts are made for developing drugs to treat and vaccines to prevent the disease. At present, there is no specific antiviral drug or vaccine for COVID-19. The pathogenic infectivity of the virus requires the S1 subunit of the spike (S) protein to bind the host cell receptor, angiontensin converting enzyme (ACE2). While the binding to host cell receptor is the first step of infection, the entrance of the virus into the cell needs the cleavage of S1–S2 subunits to expose S2 for fusion to cell membrane via host proteases including cathepsins, cell surface transmembrane protease/serine (TMPRSS) proteases, furin, trypsin and factor Xa. Previous in vitro studies have shown that factor Xa inhibition can decrease viral infectivity. We suppose that host cell proteases including furin (as expressed highly in lungs), factor Xa and cathepsin are possible targets to decrease viral burden, therefore unfractioned heparin and low molecular weight heparin-LMWH (specifically dalteparin and tinzaparin for their anti inflammatory action) can be potential inhibitors of multiple endoproteases involved in virus infectivity. Our hypothesis needs to be tested in in vitro and clinical studies, however as we are in an urgent situation as the burden of SARS-CoV2 is increasing all around the world, we recommend the usage of unfractioned heparin or LMWH in intensive care unit (ICU) and non-ICU hospitalized patients with the risk–benefit judgement of the clinician. Whether our hypothesis is clinically applicable and successful in decreasing viral infection will be evaluated for further studies. Elsevier Ltd. 2020-09 2020-04-20 /pmc/articles/PMC7169882/ /pubmed/32335456 http://dx.doi.org/10.1016/j.mehy.2020.109743 Text en © 2020 Elsevier Ltd. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Belen-Apak, F.B.
Sarialioglu, F.
The old but new: Can unfractioned heparin and low molecular weight heparins inhibit proteolytic activation and cellular internalization of SARS-CoV2 by inhibition of host cell proteases?
title The old but new: Can unfractioned heparin and low molecular weight heparins inhibit proteolytic activation and cellular internalization of SARS-CoV2 by inhibition of host cell proteases?
title_full The old but new: Can unfractioned heparin and low molecular weight heparins inhibit proteolytic activation and cellular internalization of SARS-CoV2 by inhibition of host cell proteases?
title_fullStr The old but new: Can unfractioned heparin and low molecular weight heparins inhibit proteolytic activation and cellular internalization of SARS-CoV2 by inhibition of host cell proteases?
title_full_unstemmed The old but new: Can unfractioned heparin and low molecular weight heparins inhibit proteolytic activation and cellular internalization of SARS-CoV2 by inhibition of host cell proteases?
title_short The old but new: Can unfractioned heparin and low molecular weight heparins inhibit proteolytic activation and cellular internalization of SARS-CoV2 by inhibition of host cell proteases?
title_sort old but new: can unfractioned heparin and low molecular weight heparins inhibit proteolytic activation and cellular internalization of sars-cov2 by inhibition of host cell proteases?
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169882/
https://www.ncbi.nlm.nih.gov/pubmed/32335456
http://dx.doi.org/10.1016/j.mehy.2020.109743
work_keys_str_mv AT belenapakfb theoldbutnewcanunfractionedheparinandlowmolecularweightheparinsinhibitproteolyticactivationandcellularinternalizationofsarscov2byinhibitionofhostcellproteases
AT sarialiogluf theoldbutnewcanunfractionedheparinandlowmolecularweightheparinsinhibitproteolyticactivationandcellularinternalizationofsarscov2byinhibitionofhostcellproteases
AT belenapakfb oldbutnewcanunfractionedheparinandlowmolecularweightheparinsinhibitproteolyticactivationandcellularinternalizationofsarscov2byinhibitionofhostcellproteases
AT sarialiogluf oldbutnewcanunfractionedheparinandlowmolecularweightheparinsinhibitproteolyticactivationandcellularinternalizationofsarscov2byinhibitionofhostcellproteases