tetano
Editor, Senior Moderator
J Med Virol. 2020 May 8. doi: 10.1002/jmv.25987. [Epub ahead of print]
In silico studies on the comparative characterization of the interactions of SARS-CoV-2 spike glycoprotein with ACE-2 receptor homologs and human TLRs.
Choudhury A[SUP]1[/SUP], Mukherjee S[SUP]1[/SUP].
Author information
Abstract
COVID-19 outbreak due to novel coronavirus or SARS-CoV-2 infection has come out as a major threat for mankind in recent times. It is continually taking enormous toll on mankind by means of increasing number of deaths, associated co-morbidities and socio-economic loss around the globe. Unavailability of chemotherapeutics/vaccine has posed tremendous challenges to the scientists and doctors for developing urgent therapeutic strategy. In this connection, the present in silico study aims to understand the sequence divergence of spike protein (the major infective protein of SARS-CoV-2), its mode of interaction with the angiotensin-converting enzyme-2 receptor (ACE2) receptor of human and related animal hosts/reservoir. Moreover, involvement of the human Toll- like receptors (TLRs) against the spike protein has also been demonstrated. Our data indicated that the spike glycoprotein of SARS-CoV-2 is phylogenetically close to bat coronavirus and strongly binds with ACE2 receptor protein from both human and bat origin. We have also found that cell surface TLRs, especially TLR4 is most likely to be involved in recognizing molecular patterns from SARS-CoV-2 to induce inflammatory responses. The present study supported the zoonotic origin of SARS-CoV-2 from bat and also revealed that TLR4 may have a crucial role in the virus-induced inflammatory consequences associated with COVID-19. Therefore, selective targeting of TLR4-spike protein interaction by designing competitive TLR4-antagonists could pave a new way to treat COVID-19. Finally, this study is expected to improve our understanding on the immunobiology of SARS-CoV-2 and could be useful in adopting spike protein, ACE2 or TLR-guided intervention strategy against COVID-19 shortly. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
KEYWORDS:
ACE-2 receptor; Human TLRs; Phylogeny; SARS-CoV-2; Spike glycoprotein; Therapeutic intervention
PMID:32383269DOI:10.1002/jmv.25987
In silico studies on the comparative characterization of the interactions of SARS-CoV-2 spike glycoprotein with ACE-2 receptor homologs and human TLRs.
Choudhury A[SUP]1[/SUP], Mukherjee S[SUP]1[/SUP].
Author information
Abstract
COVID-19 outbreak due to novel coronavirus or SARS-CoV-2 infection has come out as a major threat for mankind in recent times. It is continually taking enormous toll on mankind by means of increasing number of deaths, associated co-morbidities and socio-economic loss around the globe. Unavailability of chemotherapeutics/vaccine has posed tremendous challenges to the scientists and doctors for developing urgent therapeutic strategy. In this connection, the present in silico study aims to understand the sequence divergence of spike protein (the major infective protein of SARS-CoV-2), its mode of interaction with the angiotensin-converting enzyme-2 receptor (ACE2) receptor of human and related animal hosts/reservoir. Moreover, involvement of the human Toll- like receptors (TLRs) against the spike protein has also been demonstrated. Our data indicated that the spike glycoprotein of SARS-CoV-2 is phylogenetically close to bat coronavirus and strongly binds with ACE2 receptor protein from both human and bat origin. We have also found that cell surface TLRs, especially TLR4 is most likely to be involved in recognizing molecular patterns from SARS-CoV-2 to induce inflammatory responses. The present study supported the zoonotic origin of SARS-CoV-2 from bat and also revealed that TLR4 may have a crucial role in the virus-induced inflammatory consequences associated with COVID-19. Therefore, selective targeting of TLR4-spike protein interaction by designing competitive TLR4-antagonists could pave a new way to treat COVID-19. Finally, this study is expected to improve our understanding on the immunobiology of SARS-CoV-2 and could be useful in adopting spike protein, ACE2 or TLR-guided intervention strategy against COVID-19 shortly. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
KEYWORDS:
ACE-2 receptor; Human TLRs; Phylogeny; SARS-CoV-2; Spike glycoprotein; Therapeutic intervention
PMID:32383269DOI:10.1002/jmv.25987