The Interference between SARS-CoV-2 and Tyrosine Kinase Receptor Signaling in Cancer

Abstract

Cancer and viruses have a long history that has evolved over many decades. Much information about the interplay between viruses and cell proliferation and metabolism has come from the history of clinical cases of patients infected with virus-induced cancer. In addition, information from viruses used to treat some types of cancer is valuable. Now, since the global coronavirus pandemic erupted almost a year ago, the scientific community has invested countless time and resources to slow down the infection rate and diminish the number of casualties produced by this highly infectious pathogen. A large percentage of cancer cases diagnosed are strongly related to dysregulations of the tyrosine kinase receptor (TKR) family and its downstream signaling pathways. As such, many therapeutic agents have been developed to strategically target these structures in order to hinder certain mechanisms pertaining to the phenotypic characteristics of cancer cells such as division, invasion or metastatic potential. Interestingly, several authors have pointed out that a correlation between coronaviruses such as the SARS-CoV-1 and -2 or MERS viruses and dysregulations of signaling pathways activated by TKRs can be established. This information may help to accelerate the repurposing of clinically developed anti-TKR cancer drugs in COVID-19 management. Because the need for treatment is critical, drug repurposing may be an advantageous choice in the search for new and efficient therapeutic compounds. This approach would be advantageous from a financial point of view as well, given that the resources used for research and development would no longer be required and can be potentially redirected towards other key projects. This review aims to provide an overview of how SARS-CoV-2 interacts with different TKRs and their respective downstream signaling pathway and how several therapeutic agents targeted against these receptors can interfere with the viral infection. Additionally, this review aims to identify if SARS-CoV-2 can be repurposed to be a potential viral vector against different cancer types.

Targeting the PI3K/AKT pathway: a potential new weapon in the global fight against SARS-CoV-2?

“…Perhaps not surprisingly, the downstream signalling cascades elicited by cytokines systemically increased in severe COVID-19 have been found to crosstalk with pathways involved in cancer 7 and in fact the present authors have shown that increased AKT1 mRNA levels correlated with poor prognosis in several types of cancer. The PI3K pathway is one of the most commonly activated signalling pathways in estrogen receptor-positive breast cancer 8 .…”

Phage-Displayed Mimotopes of SARS-CoV-2 Spike Protein Targeted to Authentic and Alternative Cellular Receptors

“…We evaluated the performance of phage mimicry using representatives of major classes of cell surface receptors, which mediate entry of coronaviruses into the host cells: (1) metallopeptidases, including angiotensin-converting enzyme 2 (ACE2) [1,26], and (2) growth factor receptors, including fibroblast growth factor receptor 3 (FGFR3) [35,37,[78][79][80][81].…”

“…The revealed importance of CD147 in virus infection inspired a search for other potential receptors of the SARS-CoV-2 virus using computational methods [106]. A representative member of the GFR family-fibroblast growth factor receptors (FGFRs)are TKRs that play an important role in cell proliferation, migration, differentiation, and carcinogenesis [80], and are also found to be relevant in viral infections, for example, during endocytosis of the adeno-associated virus 2, and can be considered as a reserve receptor for SARS-CoV-2.…”

“…We evaluated the performance of the phage mimicry approach in the preparation of phage-derived probes targeted to a representative of the GFR family-fibroblast growth factor receptors (FGFR) [80]. Following the phage mimicry strategy, we assumed that if selected cell-associated phage mimotopes are related, for example, to FGF1 or NRP1 (the natural partners of FGFR3 [81,[85][86][87][88]), then they can be related to the mimotopes of the spike S protein, which also bind to FGFR3.…”

Target Specific Inhibition of Protein Tyrosine Kinase in Conjunction With Cancer and SARS-COV-2 by Olive Nutraceuticals

“…In SARS-CoV-2 pandemic the Growth factor receptors (GFRs) with intrinsic protein kinase activity are in much consideration. GFRs are relevant for the entry of multiple viruses, including coronaviruses, which makes them a central topic of discussion regarding the SARS-CoV-2 pandemic ( Purcaru et al, 2021 ).…”