Potential anti-tumor immune response mechanisms of SARS-CoV-2 in lymphomas: can the devil be converted into a boon? (preprint)

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 computational approach show that (i) SARS-CoV-2 Spike-RBD may bind to extracellular domains of CD15, CD27, CD45, and CD152 receptors of cHL or FL, (ii) upon internalization, 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) M protein may also interact with TUBG1 blocking its binding to GCP3, (iv) both M and Orf3a may render the GCP2-GCP3 lateral binding where M possibly interacts with GCP2 at its GCP3 binding site and Orf3a to GCP3 at its GCP2 interacting residues, (v) interactions of M and Orf3a with these gamma-tubulin ring complex components potentially block the initial process of microtubule nucleation, leading to cell cycle arrest and apoptosis, (vi) 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 proteins and may regulate the LMP-1 mediated cell proliferation. Taken together, our results suggest a possible therapeutic potential of SARS-CoV-2 in proliferative disorders.

Emergence of Unique SARS-CoV-2 ORF10 Variants and Their Impact on Protein Structure and Function (preprint)

The devastating impact of the ongoing coronavirus disease 2019 (COVID-19) on public health, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has made fighting of the COVID-19 pandemic is a top priority in medical research and pharmaceutical development. Surveillance of SARS-CoV-2 mutations is essential for the comprehension of SARS-CoV-2 variant diversity and their impact on virulence and pathogenicity. The SARS-CoV-2 open reading frame 10 (ORF10) protein interacts with multiple human proteins CUL2, ELOB, ELOC, MAP7D1, PPT1, RBX1, THTPA, TIMM8B, and ZYG11B expressed in the lung tissues. Mutations and co-mutations in the emerging SARS-CoV-2 ORF10 variants are expected to impact the severity of the virus and its associated consequences. In this article, We highlight 128 single mutations and 35 co-mutations in the unique SARS-CoV-2 ORF10 variants in this article. The possible predicted effects of these mutations and co-mutations on the secondary structure of ORF10 variants and host protein interactomes are presented. The findings highlight the possible effects of mutations and co-mutations on the emerging 140 ORF10 unique variants from secondary structure and intrinsic protein disorder perspectives.