tetano
Editor, Senior Moderator
J Med Virol
. 2021 Apr 14.
doi: 10.1002/jmv.27019. Online ahead of print.
Targeting the viral-entry facilitators of SARS-CoV-2 as a therapeutic strategy in COVID-19
Shibi Muralidar[SUP] 1 2 [/SUP], Gayathri Gopal[SUP] 1 2 [/SUP], Senthil Visaga Ambi[SUP] 1 2 [/SUP]
Affiliations
Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative agent of COVID-19 infection which has emerged as a global pandemic causing serious concerns. Lack of specific and effective therapeutics for the treatment of COVID-19 is a major concern and the development of vaccines is another important aspect in managing the infection effectively. The first step in the SARS-CoV-2 pathogenesis is the viral entry and it is mediated by its densely glycosylated spike protein (S-protein). Similar to the SARS-CoV, SARS-CoV-2 also engages angiotensin-converting enzyme 2 (ACE2) as the host cell entry receptor. In addition to ACE2, several recent studies have implicated the crucial role cell surface heparan sulfate (HS) as a necessary assisting co-factor for ACE2-mediated SARS-CoV-2 entry. Furthermore, SARS-CoV-2 was also identified to use both endosomal cysteine proteases cathepsin B and L (CatB/L) and the transmembrane serine protease 2 (TMPRSS2) for the pivotal role of S-protein priming mediating viral entry. As the entry of SARS-CoV-2 into host cells is mandatory for viral infection, it becomes an extremely attractive therapeutic intervention point. In this regard, this review will focus on the therapeutic targeting of the crucial steps of SARS-CoV-2 viral entry like S-protein/ACE2 interaction and S-protein priming by host cell proteases. In addition, this review will also give insights to the readers on several therapeutic opportunities, pharmacological targeting of the viral-entry facilitators like S-Protein, ACE2, cell surface HS, TMPRSS2, and CatB/L and evidence for those drugs currently ongoing clinical studies. This article is protected by copyright. All rights reserved.
Keywords: ACE2; CatB/L; S-protein; SARS-CoV-2; TMPRSS2; clinical trials; heparan sulfate.
. 2021 Apr 14.
doi: 10.1002/jmv.27019. Online ahead of print.
Targeting the viral-entry facilitators of SARS-CoV-2 as a therapeutic strategy in COVID-19
Shibi Muralidar[SUP] 1 2 [/SUP], Gayathri Gopal[SUP] 1 2 [/SUP], Senthil Visaga Ambi[SUP] 1 2 [/SUP]
Affiliations
- PMID: 33851732
- DOI: 10.1002/jmv.27019
Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative agent of COVID-19 infection which has emerged as a global pandemic causing serious concerns. Lack of specific and effective therapeutics for the treatment of COVID-19 is a major concern and the development of vaccines is another important aspect in managing the infection effectively. The first step in the SARS-CoV-2 pathogenesis is the viral entry and it is mediated by its densely glycosylated spike protein (S-protein). Similar to the SARS-CoV, SARS-CoV-2 also engages angiotensin-converting enzyme 2 (ACE2) as the host cell entry receptor. In addition to ACE2, several recent studies have implicated the crucial role cell surface heparan sulfate (HS) as a necessary assisting co-factor for ACE2-mediated SARS-CoV-2 entry. Furthermore, SARS-CoV-2 was also identified to use both endosomal cysteine proteases cathepsin B and L (CatB/L) and the transmembrane serine protease 2 (TMPRSS2) for the pivotal role of S-protein priming mediating viral entry. As the entry of SARS-CoV-2 into host cells is mandatory for viral infection, it becomes an extremely attractive therapeutic intervention point. In this regard, this review will focus on the therapeutic targeting of the crucial steps of SARS-CoV-2 viral entry like S-protein/ACE2 interaction and S-protein priming by host cell proteases. In addition, this review will also give insights to the readers on several therapeutic opportunities, pharmacological targeting of the viral-entry facilitators like S-Protein, ACE2, cell surface HS, TMPRSS2, and CatB/L and evidence for those drugs currently ongoing clinical studies. This article is protected by copyright. All rights reserved.
Keywords: ACE2; CatB/L; S-protein; SARS-CoV-2; TMPRSS2; clinical trials; heparan sulfate.