Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology (IIOAB), Nonakuri, Purba Medinipur 721172, West Bengal, India.
Department of Genetics, Ecology and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil.
Viruses. 2021 Sep 25;13(10):1927. doi: 10.3390/v13101927.
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 M, 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.
最近，有两例经典霍奇金淋巴瘤（cHL）和滤泡性淋巴瘤（FL）在 SARS-CoV-2 感染后完全缓解的病例报告。然而，这种罕见事件的确切分子机制尚不清楚。在这里，我们假设 SARS-CoV-2 可能具有抗肿瘤免疫反应，并基于计算方法表明：（i）SARS-CoV-2 的 Spike-RBD 可能与 cHL 或 FL 的 CD15、CD27、CD45 和 CD152 受体的细胞外结构域结合，并可能直接抑制细胞增殖。（ii）或者，在与这些 CD 分子结合后内化，SARS-CoV-2 膜（M）蛋白和 ORF3a 可能与其微管γ-1 链（TUBG1）结合位点结合γ-微管蛋白复合物成分 3（GCP3）。（iii）M 蛋白也可能与 TUBG1 相互作用，阻止其与 GCP3 结合。（iv）M 和 ORF3a 蛋白都可能使 GCP2-GCP3 侧向结合，其中 M 蛋白可能在其 GCP3 结合位点与 GCP2 相互作用，ORF3a 蛋白在其 GCP2 相互作用残基与 GCP3 相互作用。（v）M 和 ORF3a 蛋白与这些γ-微管蛋白环复合物成分的相互作用可能阻止微管核形成的初始过程，导致细胞周期停滞和细胞凋亡。（vi）Spike-RBD 也可能与 PD-1 信号相互作用并阻断其信号，类似于 pembrolizumab 和 nivolumab 等单克隆抗体，并可能诱导 B 细胞凋亡和缓解。（vii）最后，导致 NF-κB 介导致癌的 Epstein-Barr 病毒 LMP-1 的 TRADD 相互作用的“PVQLSY”基序，可能与 SARS-CoV-2 的 M、NSP7、NSP10 和 Spike（S）蛋白相互作用，并可能抑制 LMP-1 介导的细胞增殖。综上所述，我们的结果表明 SARS-CoV-2 在淋巴增生性疾病中具有潜在的治疗作用。
