Potential Molecular Mechanisms of Rare Anti-Tumor Immune Response by SARS-CoV-2 in Isolated Cases of Lymphomas

Debmalya Barh, Sandeep Tiwari, Lucas Gabriel Rodrigues Gabriel Rodrigues Gomes, Marianna E. Weener, Khalid J. Alzahrani, Khalaf F. Alsharif, Alaa A. A. Aljabali, Murtaza M. Tambuwala, Kenneth Lundstrom, Sk. Sarif Hassan, Ángel Serrano-aroca, Kazuo Takayama, Preetam Ghosh, Elrashdy M. Redwan, Bruno Silva Silva Andrade, Siomar De Castro Soares, Vasco Azevedo, Vladimir N. Uversky

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Abstract

Recently, two cases of complete remission of classical Hodgkin lymphoma (cHL) and follicular lymphoma (FL) after SARS-CoV-2 infection were reported. However, the precise molecular mechanism of this rare event is yet to be understood. Here, we hypothesize a potential anti-tumor immune response of SARS-CoV-2 and based on a computational approach show that: (i) SARS-CoV-2 Spike-RBD may bind to the extracellular domains of CD15, CD27, CD45, and CD152 receptors of cHL or FL and may directly inhibit cell proliferation. (ii) Alternately, upon internalization after binding to these CD molecules, the SARS-CoV-2 membrane (M) protein and ORF3a may bind to gamma-tubulin complex component 3 (GCP3) at its tubulin gamma-1 chain (TUBG1) binding site. (iii) The M protein may also interact with TUBG1, blocking its binding to GCP3. (iv) Both the M and ORF3a proteins may render the GCP2-GCP3 lateral binding where the M protein possibly interacts with GCP2 at its GCP3 binding site and the ORF3a protein to GCP3 at its GCP2 interacting residues. (v) Interactions of the M and ORF3a proteins with these gamma-tubulin ring complex components potentially block the initial process of microtubule nucleation, leading to cell-cycle arrest and apoptosis. (vi) The Spike-RBD may also interact with and block PD-1 signaling similar to pembrolizumab and nivolumab- like monoclonal antibodies and may induce B-cell apoptosis and remission. (vii) Finally, the TRADD interacting “PVQLSY” motif of Epstein-Barr virus LMP-1, that is responsible for NF-kB mediated oncogenesis, potentially interacts with SARS-CoV-2 Mpro, NSP7, NSP0, and spike (S) proteins, and may inhibit the LMP-1 mediated cell proliferation. Taken together, our results suggest a possible therapeutic potential of SARS-CoV-2 in lymphoproliferative disorders.
Original languageEnglish
Article number1927
Number of pages26
JournalViruses
Volume13
Issue number10
Early online date25 Sep 2021
DOIs
Publication statusE-pub ahead of print - 25 Sep 2021

Keywords

  • lymphoma
  • canceer
  • SARS-CoV-2
  • M protein
  • ORF3a
  • anti-tumor immunotherapy
  • gamma-tubulin ring complex
  • PD-1
  • monoclonal anitbody

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