tetano
Editor, Senior Moderator
J Biomol Struct Dyn
. 2020 Sep 16;1-11.
doi: 10.1080/07391102.2020.1822208. Online ahead of print.
Molecular basis of the potential interaction of SARS-CoV-2 spike protein to CD147 in COVID-19 associated-lymphopenia
Mohamed A Helal[SUP] 1 2 [/SUP], Shaimaa Shouman[SUP] 3 [/SUP], Ahmad Abdelwaly[SUP] 1 [/SUP], Ahmed O Elmehrath[SUP] 3 4 [/SUP], Mohamed Essawy[SUP] 3 [/SUP], Shireen M Sayed[SUP] 3 [/SUP], Amr H Saleh[SUP] 1 [/SUP], Nagwa El-Badri[SUP] 3 [/SUP]
Affiliations
Abstract
Lymphopenia is considered one of the most characteristic clinical features of the coronavirus disease 2019 (COVID-19). SARS-CoV-2 infects host cells via the interaction of its spike protein with the human angiotensin-converting enzyme 2 (hACE2) receptor. Since T lymphocytes display a very low expression level of hACE2, a novel receptor might be involved in the entry of SARS-CoV-2 into T cells. The transmembrane glycoprotein CD147 is highly expressed by activated T lymphocytes, and was recently proposed as a probable route for SARS-CoV-2 invasion. To understand the molecular basis of the potential interaction of SARS-CoV-2 to CD147, we have investigated the binding of the viral spike protein to this receptor in-silico. The results showed that this binding is dominated by electrostatic interactions involving residues Arg403, Asn481, and the backbone of Gly502. The overall binding arrangement shows the CD147 C-terminal domain interacting with the spike external subdomain in the grove between the short antiparallel β strands, β1' and β2', and the small helix α1'. This proposed interaction was further confirmed using MD simulation and binding free energy calculation. These data contribute to a better understanding of the mechanism of infection of SARS-CoV-2 to T lymphocytes and could provide valuable insights for the rational design of adjuvant treatment for COVID-19. Communicated by Ramaswamy H. Sarma.
Keywords: CD147; Lymphopenia; SARS-CoV-2; docking; spike.
. 2020 Sep 16;1-11.
doi: 10.1080/07391102.2020.1822208. Online ahead of print.
Molecular basis of the potential interaction of SARS-CoV-2 spike protein to CD147 in COVID-19 associated-lymphopenia
Mohamed A Helal[SUP] 1 2 [/SUP], Shaimaa Shouman[SUP] 3 [/SUP], Ahmad Abdelwaly[SUP] 1 [/SUP], Ahmed O Elmehrath[SUP] 3 4 [/SUP], Mohamed Essawy[SUP] 3 [/SUP], Shireen M Sayed[SUP] 3 [/SUP], Amr H Saleh[SUP] 1 [/SUP], Nagwa El-Badri[SUP] 3 [/SUP]
Affiliations
- PMID: 32936048
- DOI: 10.1080/07391102.2020.1822208
Abstract
Lymphopenia is considered one of the most characteristic clinical features of the coronavirus disease 2019 (COVID-19). SARS-CoV-2 infects host cells via the interaction of its spike protein with the human angiotensin-converting enzyme 2 (hACE2) receptor. Since T lymphocytes display a very low expression level of hACE2, a novel receptor might be involved in the entry of SARS-CoV-2 into T cells. The transmembrane glycoprotein CD147 is highly expressed by activated T lymphocytes, and was recently proposed as a probable route for SARS-CoV-2 invasion. To understand the molecular basis of the potential interaction of SARS-CoV-2 to CD147, we have investigated the binding of the viral spike protein to this receptor in-silico. The results showed that this binding is dominated by electrostatic interactions involving residues Arg403, Asn481, and the backbone of Gly502. The overall binding arrangement shows the CD147 C-terminal domain interacting with the spike external subdomain in the grove between the short antiparallel β strands, β1' and β2', and the small helix α1'. This proposed interaction was further confirmed using MD simulation and binding free energy calculation. These data contribute to a better understanding of the mechanism of infection of SARS-CoV-2 to T lymphocytes and could provide valuable insights for the rational design of adjuvant treatment for COVID-19. Communicated by Ramaswamy H. Sarma.
Keywords: CD147; Lymphopenia; SARS-CoV-2; docking; spike.