key: cord-0851660-7cr98xms authors: Barbosa, Jhonatas Rodrigues; de Carvalho Junior, Raul Nunes title: Polysaccharides obtained from natural edible sources and their role in modulating the immune system: Biologically active potential that can be exploited against COVID-19 date: 2021-01-04 journal: Trends Food Sci Technol DOI: 10.1016/j.tifs.2020.12.026 sha: a6b990263ed108ddf79de763dc49f5cbd1d1f61c doc_id: 851660 cord_uid: 7cr98xms BACKGROUND: The global crisis caused by the outbreak of severe acute respiratory syndrome caused by the SARS-CoV-2 virus, better known as COVID-19, brought the need to improve the population's immunity. The foods rich in polysaccharides with immunomodulation properties are among the most highly rated to be used as immune response modulators. Thus, the use of polysaccharides obtained from food offers an innovative strategy to prevent serious side effects of viral infections. SCOPE AND APPROACH: This review revisits the current studies on the pathophysiology of SARS-CoV-2, its characteristics, target cell interactions, and the possibility of using polysaccharides from functional foods as activators of the immune response. Several natural foods are explored for the possibility of being used to obtain polysaccharides with immunomodulatory potential. And finally, we address expectations for the use of polysaccharides in the development of potential therapies and vaccines. KEY FINDINGS AND CONCLUSIONS: The negative consequences of the SARS-CoV-2 pandemic across the world are unprecedented, thousands of lives lost, increasing inequalities, and incalculable economic losses. On the other hand, great scientific advances have been made regarding the understanding of the disease and forms of treatment. Polysaccharides, due to their characteristics, have the potential to be used as potential drugs with the ability to modulate the immune response. In addition, they can be used safely, as they have no toxic effects, are biocompatible and biodegradable. Finally, these biopolymers can still be used in the development of new therapies and vaccines. in the worsening of sepsis symptoms (symptoms: include fever, difficulty breathing, 257 low blood pressure, fast heart rate, and mental confusion), responsible for more than 258 28% of deaths from SARS-CoV-2. In these cases, the condition of uncontrolled 259 inflammation causes multiple damage, mainly to the organs of the heart, liver, kidney 260 and respiratory system, making it very difficult for patients to recover (Chu et al., 2005; 261 Li et al., 2020b). 262 One of the great current challenges is to understand the role of the immune system in 263 the face of SARS-CoV-2 infection. So far we know that the protective effects of 264 immunity against SARS-CoV-2 suffer widespread failures. However, the real causes 265 and mechanisms by which the immune response is compromised in individuals with 266 SARS-CoV-2 are still unclear. In addition, the picture of infections is very varied, as 267 has been discussed previously, several types of patients can be observed, from 268 J o u r n a l P r e -p r o o f However, we know that immunity remains the Holy Grail of COVID-19 research. 270 Although the immunity of individuals appears to have a central role, we know that there 271 is still some mechanism to be identified that acts as an immune response imbalance 272 system. This has been observed and shows that even patients with good immunity can 273 progress to severe clinical conditions, although the highest mortality rate can be 274 CoV-2 infection, the immune system itself already suffers serious damage and its 284 functionality is impaired, even at the beginning of the innate immune response. What 285 has been the subject of many discussions about, what are the mechanisms for activating 286 an inadequate immune response? Therefore, in these cases, the majority of infected 287 individuals have several clinical signs of inflammation and, in several cases, processes 288 of hyperinflammation and serious impairment of vital organs. On the other hand, 289 Individuals who manage to overcome all infections properly, that is, with the immune 290 system acting in a balanced way, obtain the acquired immune response. Although it is 291 not clear how long the immune response acquired due to SARS-CoV-2 infection can 292 prevent new infections, we know that the immune system after the infection has 293 recovered is prepared to deal with possible new infections in a more balanced way (Yu 294 et al., 2020a) . To understand in more detail about immune system failures in patients 295 infected with SARS-CoV-2, we will address the recent findings by Lucas et al. (2020) , 296 in Box 1. 297 Polysaccharides are distributed throughout nature, from microorganisms to complex 299 organisms. We functional foods such as fruits, vegetables, mushrooms, algae, herbs and 300 plants in general, these biopolymers are found in abundance. In fact, in recent years, a 301 great effort has been made by researchers worldwide to understand the importance and 302 distribution of polysaccharides in natural foods. Also, considerable efforts have been 303 made to establish a well-founded understanding of the influence of polysaccharides on 304 human health. Thus, in this topic, we will address the main polysaccharides obtained 305 from natural foods, with special emphasis on their structural properties that may 306 attribute some biological potential. Meanwhile, ( were explored in the review article, with an emphasis on structural characteristics and 342 heteropolysaccharides, that is, polysaccharides with more than one type of monomer in 344 the monosaccharide chain. The study shows that hybrid mushrooms also produce 345 heteropolysaccharides. Also, heteropolysaccharides have important biological activities, 346 such as anti-tumor, antioxidant, anti-inflammatory, and immunomodulatory activity. The polysaccharide potential in modulating the immune system will be the focus of this 505 topic. Also, the polysaccharide immunomodulatory potential will be used as an 506 indication of the ability of these biopolymers to stimulate the body to improve the 507 immune response to viral infections, especially by SARS-CoV-2. Therefore, for a better 508 understanding of the reader on the subject, we will initially address important aspects of 509 inflammatory immunopathogenesis related to SARS-CoV-2 infection. Then, the main 510 polysaccharides with immunomodulatory activity will be addressed. 511 After infection of the cells by SARS-CoV-2 and therefore the destruction of lung cells, 512 the body initiates a local immune response, recruiting defense cells such as 513 macrophages and monocytes that immediately respond to infection, releasing cytokines, 514 substances that modulate the immune response. The released cytokines stimulate the 515 defense cells, adaptive T and B cells, which respond to infection, attacking 516 contaminated cells and viruses (Yang et al., 2020a) . In most cases, this process is 517 the face of the underlying biochemical phenomena. However, in some cases, the body 519 reacts differently, initiating a dysfunctional immune response, which leads to a chain 520 reaction, and causes serious complications to the lungs and even systemic pathologies, 521 which can lead to death (He et al., 2020b). 522 The virus replicates continuously in the epithelial cells of the airways, causing high 523 levels of pyroptosis, a type of programmed cell death. This is probably the trigger for 524 the localized inflammatory response. Subsequently, IL-1β, a cytokine released during 525 pyroptosis increases considerably, attracting an immediate inflammatory response. 526 Using pattern recognition receptors (PRRs), cells such as alveolar macrophages and 527 alveolar epithelial cells identify receptors for pathogens such as viral RNA, and 528 damage-associated molecular patterns (DAMPs). Thus these cells initiate localized 529 inflammation, with increased cytokines and pro-inflammatory chemokines IL-6, IFNγ, 530 MCP1, and IP-10 in the blood (Wrapp et al., 2020) . In response to the high level of pro-531 inflammatory substances, defense cells such as monocytes and T lymphocytes initiate a 532 coordinated attack at the sites of inflammation. In most cases, recruited cells can 533 respond adequately to the immune system and patients recover. However, in other 534 cases, still poorly understood, patients exhibited higher blood plasma levels of IL-2, IL-535 7, IL-10, granulocyte colony-stimulating factor (G-CSF), IP-10, MCP1, macrophage 536 inflammatory protein 1a (MIP1α) and tumor necrosis factor (TNF). The mechanism by 537 which the SARS-CoV-2 virus subverts the antiviral response is still unknown, but it is 538 known that the cytokine storm has side effects on the body, leading to septic shock and 539 multiple organ failure. Also, adults, the elderly and people with morbidities have lower 540 levels of defense cells when compared to children, therefore, the inflammatory response 541 can be harmful (Wrapp et al., 2020) . 542 asymptomatic, although the viral load is high. Around 6% develop severe symptoms, 544 however, in most cases; these children have some associated morbidity. Santos Freitas, da Silva Martins & de Carvalho Junior, 2020). 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