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Consumption of Phenolic-Rich Food and Dietary Supplements As a Key Tool in SARS-Cov-19 Infection

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Consumption of Phenolic-Rich Food and Dietary Supplements As a Key Tool in SARS-Cov-19 Infection foods Review Consumption of Phenolic-Rich Food and Dietary Supplements as a Key Tool in SARS-CoV-19 Infection José David Flores-Félix 1 , Ana C. Gonçalves 1 , Gilberto Alves 1 and Luís R. Silva 1,2,* 1 CICS-UBI–Health Sciences Research Centre, Faculty of Health Science, University of Beira Interior, 6200-506 Covilhã, Portugal; jdfl[email protected] (J.D.F.-F.); [email protected] (A.C.G.); [email protected] (G.A.) 2 Unidade de Investigação para o Desenvolvimento do Interior (UDI/IPG), Instituto Politécnico da Guarda, 6300-559 Guarda, Portugal * Correspondence: [email protected]; Tel.: +351-275-329-002 Abstract: The first cases of COVID-19, which is caused by the SARS-CoV-2, were reported in December 2019. The vertiginous worldwide expansion of SARS-CoV-2 caused the collapse of health systems in several countries due to the high severity of the COVID-19. In addition to the vaccines, the search for active compounds capable of preventing and/or fighting the infection has been the main direction of research. Since the beginning of this pandemic, some evidence has highlighted the importance of a phenolic-rich diet as a strategy to reduce the progression of this disease, including the severity of the symptoms. Some of these compounds (e.g., curcumin, gallic acid or quercetin) already showed capacity to limit the infection of viruses by inhibiting entry into the cell through its binding to protein Spike, regulating the expression of angiotensin-converting enzyme 2, disrupting the replication in cells by inhibition of viral proteases, and/or suppressing and modulating the host’s Citation: Flores-Félix, J.D.; immune response. Therefore, this review intends to discuss the most recent findings on the potential Gonçalves, A.C.; Alves, G.; Silva, L.R. of phenolics to prevent SARS-CoV-2. Consumption of Phenolic-Rich Food and Dietary Supplements as a Key Keywords: dietary supplements; COVID-19; immune response; mediterranean diet; phenolic compounds Tool in SARS-CoV-19 Infection. Foods 2021, 10, 2084. https://doi.org/ 10.3390/foods10092084 1. Introduction Academic Editor: Jose The current pandemic coronavirus disease-2019 (COVID-19) is probably the most Angel Perez-Alvarez convulsive global event in the history of mankind and it is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Its emergency occurred at the end of Received: 30 July 2021 the year 2019 in China, where the alarms about transmissibility and morbidity were lit, Accepted: 2 September 2021 because on January 19 of 2020, of the 189 people with COVID-19, only 19 did not require Published: 3 September 2021 hospitalization, and three were detected in other countries without any relation to the possible focus, which was reported as a local food market in China [1]. Publisher’s Note: MDPI stays neutral Different taxonomic studies have shown that this virus is a member of the so-called with regard to jurisdictional claims in published maps and institutional affil- SARS-related coronaviruses (SARSr-CoV) and belongs to the Coronaviridae family and iations. Betacoronavirus genus. Although this one is considered a zoonosis, the final vector has not been detected yet. However, the genomic analysis shows important similarities with other Betacoronaviruses isolated from bats, such as Rhinolophus affinis, or other mammals as civets and pangolins. Therefore, the most widespread hypothesis is that horizontal gene transfer and recombination events occurred involving bat RaTG13 and Guangdong Copyright: © 2021 by the authors. pangolin coronaviruses, and bat CoV ZC45 and ZXC21 strains [2–5]. Licensee MDPI, Basel, Switzerland. In a general way, the SARS-CoV-2 is composed of open reading frames, where Open This article is an open access article distributed under the terms and Reading Frame 1a and 1b (ORF1a and ORF1b, respectively) are responsible to encode 0 conditions of the Creative Commons polyproteins of the SARS-CoV-2 genome at the 5 end (Figure1), including the non- pro pro pro Attribution (CC BY) license (https:// structural 3-chymotrypsin-like protease (3CL or M ), papain-like protease (PL ) creativecommons.org/licenses/by/ and RNA-dependent RNA polymerase (RdRp). In the other side of the virus chain, i.e., 0 4.0/). at the terminal 3 , there are found ORFs that encode the viral surface proteins, namely Foods 2021, 10, 2084. https://doi.org/10.3390/foods10092084 https://www.mdpi.com/journal/foods Foods 2021, 10, x FOR PEER REVIEW 2 of 20 Foods 10 2021, , 2084 RNA-dependent RNA polymerase (RdRp). In the other side of the virus chain, i.e., at2 ofthe 19 terminal 3′, there are found ORFs that encode the viral surface proteins, namely the Spike (S), envelope (E), membrane (M) and nucleocapsid (N) proteins [6]. Like other SARSr- CoVs,the Spike SARS-CoV-2 (S), envelope also (E), uses membrane the highly (M) andglycosylated nucleocapsid S protein (N) proteins located [6 ].on Like its otherviral membraneSARSr-CoVs, to bind SARS-CoV-2 the host also cell usesreceptor, the highly the angiotensin-converting glycosylated S protein enzyme located onII (ACE2), its viral andmembrane thus, enter to bind into the the host human cell body receptor, [7]. theThis angiotensin-converting enzyme is present in the enzyme membrane II (ACE2), of many and cellsthus, of enter different into the organs human and body plays [7]. a Thiscrucial enzyme role in is presentthe regulation in the membrane of blood pressure of many cellsand electrolyteof different balance organs and[8]. playsThe linkage a crucial of role the inS pr theotein regulation generates of blood an inactivation pressure and of electrolytethe ACE2 protein,balance causing [8]. The an linkage imbalance of the in S proteinthe propor generatestion of anpeptides inactivation generated of the by ACE2 angiotensin- protein, convertingcausing an imbalanceenzyme I (ACE1) in the proportion and ACE2, of and peptides triggering generated a pre-inflammatory by angiotensin-converting response, whichenzyme causes, I (ACE1) in most and ACE2,cases, symptoms and triggering simila a pre-inflammatoryr to flu [8,9]. Additionally, response, whichtransmembrane causes, in proteasemost cases, serine symptoms 2, which similar is an enzyme to flu [ 8enco,9]. Additionally,ded by the TMPRSS2 transmembrane gene in humans, protease is serine also involved2, which isin anthe enzyme cleavage encoded of S protein by the and TMPRSS2 ACE2, allowing gene in humans, the viral is endocytose also involved [10]. in The the infectioncleavage ofwith S protein this virus and promotes ACE2, allowing the appearance the viral endocytoseof fever, dry [10 cough,]. The infectionfatigue, dyspnea, with this myalgias,virus promotes headache, the appearance sore throat, of fever, rhinorrhea, dry cough, and fatigue, gastrointestinal dyspnea, myalgias, symptoms headache, [6]. Sometimes,sore throat, rhinorrhea,the exaggerated and gastrointestinaland uncontrolled symptoms immune [ 6system]. Sometimes, response, the compromise exaggerated vitaland uncontrolledfunctions and immune damage system organs, response, leading compromise to the development vital functions of pneumonia and damage and or- eventualgans, leading death, to independently the development of ofage, pneumonia gender, and and health eventual condition. death, independently Furthermore, ofa characteristicage, gender, andthat health makes condition. this disease Furthermore, remarkable a characteristic is the appearance that makes of this persistent disease symptoms.remarkable Indeed, is the appearance statistical ofdata persistent indicates symptoms. that around Indeed, 50% of statistical the infected data do indicates not return that toaround their initial 50% of health the infected state, presenting do not return contin to theiruous initial fatigue health and state, higher presenting levels of continuousC-reactive proteinfatigue and lactate higher dehydrogenase, levels of C-reactive which protein can be and synonyms lactate dehydrogenase, with cell death [9]. which can be synonyms with cell death [9]. Figure 1. Genomic scheme of SARS-CoV-2 genome. Figure 1. Genomic scheme of SARS-CoV-2 genome. Normally, the COVID-19 is treated with paracetamol. However, it is well-known that the continuousNormally, intakethe COVID-19 of pharmaceutical is treated drugswith para is notcetamol. recommended However, due it tois well-known their undesirable that theside continuous effects. Additionally, intake of and pharmaceutical since it is also recognizeddrugs is not that recommended the rapid spread due of theto virustheir undesirablethroughout theside world effects. collapsed Additionally, most healthand since systems it is also and recognized decreased economicthat the rapid activities spread of ofthe the countries, virus throughout several efforts the world have collapsed been done most to attenuate, health systems or even and mitigate, decreased this pandemiceconomic activitiesdisease [11 of, 12the]. Incountries, this order several of ideas, efforts it is nothave surprising been done that to otherattenuate, therapeutical or even strategiesmitigate, thisare beingpandemic studied disease anddeveloped, [11,12]. In includingthis order those of ideas, based it on is phenolics. not surprising In fact, that phenolics other therapeuticalpresent several strategies advantages, are as being low toxicity,studied predominance and developed, in nature, including and abilitiesthose based to relieve on phenolics.oxidative stress,In fact, reduce phenolics inflammatory present several markers advantages, and restore as the low immune
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