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In silico studies on the comparative characterization of the interactions of SARS-CoV-2 spike glycoprotein with ACE-2 receptor homologs and human TLRs.
J Med Virol. 2020 10; 92(10):2105-2113.JM

Abstract

Coronavirus disease-2019 (COVID-19) outbreak due to novel coronavirus or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has come out as a major threat for mankind in recent times. It is continually taking an enormous toll on mankind by means of increasing number of deaths, associated comorbidities, and socioeconomic loss around the globe. Unavailability of chemotherapeutics/vaccine has posed tremendous challenges to scientists and doctors for developing an 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, the 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 a 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.

Authors+Show Affiliations

Department of Animal Science, Integrative Biochemistry and Immunology Laboratory, Kazi Nazrul University, Asansol, West Bengal, India.Department of Animal Science, Integrative Biochemistry and Immunology Laboratory, Kazi Nazrul University, Asansol, West Bengal, India.

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

32383269

Citation

Choudhury, Abhigyan, and Suprabhat Mukherjee. "In Silico Studies On the Comparative Characterization of the Interactions of SARS-CoV-2 Spike Glycoprotein With ACE-2 Receptor Homologs and Human TLRs." Journal of Medical Virology, vol. 92, no. 10, 2020, pp. 2105-2113.
Choudhury A, Mukherjee S. In silico studies on the comparative characterization of the interactions of SARS-CoV-2 spike glycoprotein with ACE-2 receptor homologs and human TLRs. J Med Virol. 2020;92(10):2105-2113.
Choudhury, A., & Mukherjee, S. (2020). In silico studies on the comparative characterization of the interactions of SARS-CoV-2 spike glycoprotein with ACE-2 receptor homologs and human TLRs. Journal of Medical Virology, 92(10), 2105-2113. https://doi.org/10.1002/jmv.25987
Choudhury A, Mukherjee S. In Silico Studies On the Comparative Characterization of the Interactions of SARS-CoV-2 Spike Glycoprotein With ACE-2 Receptor Homologs and Human TLRs. J Med Virol. 2020;92(10):2105-2113. PubMed PMID: 32383269.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In silico studies on the comparative characterization of the interactions of SARS-CoV-2 spike glycoprotein with ACE-2 receptor homologs and human TLRs. AU - Choudhury,Abhigyan, AU - Mukherjee,Suprabhat, Y1 - 2020/05/17/ PY - 2020/04/24/received PY - 2020/05/05/accepted PY - 2020/5/10/pubmed PY - 2020/12/30/medline PY - 2020/5/9/entrez KW - ACE-2 receptor KW - SARS-CoV-2 KW - human TLRs KW - phylogeny KW - spike glycoprotein KW - therapeutic intervention SP - 2105 EP - 2113 JF - Journal of medical virology JO - J Med Virol VL - 92 IS - 10 N2 - Coronavirus disease-2019 (COVID-19) outbreak due to novel coronavirus or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has come out as a major threat for mankind in recent times. It is continually taking an enormous toll on mankind by means of increasing number of deaths, associated comorbidities, and socioeconomic loss around the globe. Unavailability of chemotherapeutics/vaccine has posed tremendous challenges to scientists and doctors for developing an 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, the 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 a 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. SN - 1096-9071 UR - https://www.unboundmedicine.com/medline/citation/32383269/In_silico_studies_on_the_comparative_characterization_of_the_interactions_of_SARS_CoV_2_spike_glycoprotein_with_ACE_2_receptor_homologs_and_human_TLRs_ L2 - https://doi.org/10.1002/jmv.25987 DB - PRIME DP - Unbound Medicine ER -