Lymphoma, Cancer, Sars-cov-2, M Protein, Orf3a, Anti-tumor Immunotherapy, Gamma-tubulin Ring Complex, PD-1, Monoclonal Antibody
Digital Object Identifier (DOI)
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, NSP10, 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.
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Citation / Publisher Attribution
Viruses, v. 13, issue 10, art. 1927
Scholar Commons Citation
Barh, Debmalya; Tiwary, Sandeep; Gomes, Lucas Gabriel Rodrigues; Weener, Marianna E.; Alzahrani, Khalid J.; Alsharif, Khalaf F.; Aljabali, Alaa A. A.; Tambuwala, Murtaza M.; Lundstrom, Kenneth; Hassan, Sk. Sarif; Serrano-Aroca, Ángel; Takayama, Kazuo; Ghosh, Preetam; Redwan, Elrashdy M.; Andrade, Bruno Silva; Soares, Siomar de Castro; Azevedo, Vasco; and Uversky, Vladimir N., "Potential Molecular Mechanisms of Rare Anti-tumor Immune Response by SARS-CoV-2 in Isolated Cases of Lymphomas" (2021). Molecular Medicine Faculty Publications. 896.