Coronavirus and Carbon Nanotubes: Seeking Immunological Relationships to Discover Immunotherapeutic Possibilities

Figures & data

Figure 1 Continue.

Figure 1 Immune activation by coronavirus.

Notes: (A–C) The immune response to infections by different coronaviruses, where the different cell types recruited and activated cytokines involved in the inflammatory processes during this infection are shown. Data from references ¹¹, ¹⁴, ¹⁷, ²⁰, ²⁵, ³¹, ⁴⁵, and ⁵⁵.

Table 1 Comparison of Immune Characteristics of the Three Recent Coronavirus Outbreaks and CNTs

General Aspects	SARS-CoV	MERS-CoV	SARS-CoV-2	CNTs
Genus	Betacoronavirus^Citation85	Betacoronavirus^Citation85	Betacoronavirus^Citation85	-
Mortality	9.6%^Citation89	34.4%^Citation89	Estimated in 2%^Citation89	-
Year of origin	2002^Citation8	2012^Citation8	2019^Citation8	1991^Citation64
Receptor	ACE2^Citation39	DPP4^Citation39	ACE2^Citation39	They show the ability to bind to the active protease site of HIV, blocking its function.^Citation87
Cells target	Airway epithelial ciliated cells and type 2 alveolar pneumocytes.^Citation88	Pneumocytes and syncytial epithelial cells.^Citation88	Cells with receptor ACE2, especially airway epithelial ciliated cells, and type 2 alveolar pneumocytes.^Citation88	Potentially macrophages, NK cells, monocytes, DCs, T cells, and components of the complement system.^Citation92,^Citation190
Main cytokines and chemokines secreted	IL-1, TNF-α, IL-6, IFN-α/γ, CCL2, CCL3, CCL5, CXCL10, IL-8; IFN type I, and Type II.^Citation44	IFN-α/γ, IL-6, IL-8, IL-12, IL-1β, TNF-α, IL-6, CXCL10, CCL-2/3 and 5 and IL- 8.^Citation89	IL-6, TNF-α, MIP1-α, MCP-3, GM-CSF, IL-2, IFN type I and type II, IP10, CCL2, CXCL1, and CXCL5.^Citation26	DWNTs induced IL-1β linked to caspase-1 and activation of the NLRP3 inflammasome; f-MWCNTs induced the expression of CD25 activation markers and release of IL-1β, IL-6, TNF, and IL-10 by CD14+ monocytes not accompanied by the activation of cytotoxic mechanisms. f-CNTs activated molecular pathways, such as the Toll-like receptor (TLR).^Citation91,^Citation207
Impacts on the immune system	Viral proteins antagonize the IFN response, induce T cell apoptosis, and delay T cells response, especially that of CD8+ T cells.^Citation45	Suppresses of the innate immune system and interferons; induces apoptosis of CD4+ and CD8+ T cells; increases cytokines levels in macrophages, DCs, and T cells.^Citation89,^Citation207	Bypasses the innate immune system and interferon antiviral response; delay T-cell responses (particularly CD8+ T cells); decreases DCs and NK cells in severe cases.^Citation26,^Citation60	Can interact with components of the immune system and with soluble plasma proteins to form a coronal structure around them, altering their interaction with cells in the complement system. Complement proteins (C1q, MBL and C-reactive protein) can recognize the surface of functionalized CNTs.^Citation79,^Citation91
T cells	Produce pro-inflammatory cytokines via the NF-kB pathway.^Citation208	CD8+ T-cell responses can be detected without antibody responses.^Citation208	CD4+ T cells increase anti-S-RBD IgG and IgA. CD8+ T cells eliminate the virus when antibody action is reduced. Decreases of regulatory and memory T cells lead to increases in cytokines.^Citation208	Deliver siRNA for efficient RNAi of CXCR4 and CD4 receptors in human T cells and peripheral blood mononuclear cells (PBMCs).^Citation94
Antibodies	Specific to the RBD domain of protein S. Decrease after 1/2 year.^Citation208	Strong affinity for the spike protein. They facilitate viral entry by antibody-dependent potentiation (ADE). IgM and IgG levels are increased in the first week. IgM level gradually decreases. No detection after 6 years.^Citation208	The main target is protein S, but there are antibodies against nucleocapsid protein (N). Persistence is uncertain, with decreases observed months later.^Citation208	Bind to the B cell epitope and, increase the amount of antibody-producing B cells to modulate the immune response.^Citation93,^Citation119

Figure 2 Immune relationship between coronavirus and CNTs.

Notes: Immunological relationship between the immune response induced by coronavirus infection, and the immune response induced by CNTs. Data from references ⁸⁴, ⁸⁹, and ⁹¹.

Figure 3 Continue.

Figure 3 Continue.

Figure 3 Continue.

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Figure 3 CNTs use in immunotherapy.

Notes: (A–E) Advances in research using CNTs as immunotherapeutic agents through RNAi and in treatments/vaccines of different viral infections. Data from references ⁸⁹, ⁹³, and ^96–102.

Figure 4 Challenges in using CNTs as immunotherapeutic agents.

Notes: The challenges of using nanotubes as immunotherapeutic agents include cytotoxicity, biodistribution and elimination of the nanomaterials from biological systems. Data from references ^173–176.

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