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Molecular basis of the potential interaction of SARS-CoV-2 spike protein to CD147 in COVID-19 associated-lymphopenia

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posted on 16.09.2020 by Mohamed A. Helal, Shaimaa Shouman, Ahmad Abdelwaly, Ahmed O. Elmehrath, Mohamed Essawy, Shireen M. Sayed, Amr H. Saleh, Nagwa El-Badri

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

Funding

The authors would like to thank the Bibliotheca Alexandrina, Alexandria, Egypt for providing access to the High-Performance Computing Cluster which was used for the molecular dynamics simulation part of the study, ASRT grant #7301 for partial funding, and internal funding ZC003-2019 from Zewail City for Science and Technology.

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