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Intermittent fasting, a possible priming tool for host defense against SARS-CoV-2 infection: crosstalk among calorie restriction, autophagy and immune response

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Abstract and Figures

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative pathogen of deadly Coronavirus disease-19 (COVID-19) pandemic, which emerged as a major threat to public health across the world. Although there is no clear gender or socioeconomic discrimination in the incidence of COVID-19, individuals who are older adults and/or with comorbidities and compromised immunity have a relatively higher risk of contracting this disease. Since no specific drug has yet been discovered, strengthening immunity along with maintaining a healthy living is the best way to survive this disease. As a healthy practice, calorie restriction in the form of intermittent fasting in several clinical settings has been reported to promote several health benefits, including priming of the immune response. This dietary practice also activates autophagy, a cell surveillance system that boosts up immunity. With these prevailing significance in priming host defense, intermittent fasting could be a potential strategy amid this outbreak to fighting off SARS-CoV-2 infection. Currently, no review so far available proposing intermittent fasting as an encouraging strategy in the prevention of COVID-19. A comprehensive review has therefore been planned to highlight the beneficial role of fasting in immunity and autophagy, that underlie the possible defense against SARS-CoV-2 infection. The COVID-19 pathogenesis and its impact on host immune response have also been briefly outlined. This review aimed at revisiting the immunomodulatory potential of intermittent fasting that may constitute a promising preventive strategy against COVID-19.
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Review Article
Intermittent fasting, a possible priming tool for host defense against SARS-CoV-2 infection:
crosstalk among calorie restriction, autophagy and immune response
Md. Abdul Hannan1,2,3, Md. Ataur Rahman2,4,5, Md Saidur Rahman2,6, Abdullah Al Mamun Sohag1,
Raju Dash3, Khandkar Shaharina Hossain2,7, Mithila Farjana2,7, Md Jamal Uddin2,8*
1Department of Biochemistry and Molecular Biology, Bangladesh Agricultural University,
Mymensingh-2202, Bangladesh;
2ABEx Bio-Research Center, East Azampur, Dhaka-1230, Bangladesh;
3Department of Anatomy, Dongguk University College of Medicine, Gyeongju 38066, Korea;
4Center for Neuroscience, Korea Institute of Science and Technology (KIST), Seoul 02792,
Republic of Korea;
5Global Biotechnology & Biomedical Research Network (GBBRN), Dept. of Biotechnology and
Genetic Engineering, Islamic University, Kushtia 7003, Bangladesh;
6Department of Animal Science & Technology and BET Research Institute, Chung-Ang
University, Anseong 456-756, Republic of Korea;
7Biotechnology and Genetic Engineering Discipline, Khulna University, Khulna 9208, Bangladesh;
8Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University,
Seoul 03760, Republic of Korea.
*Corresponding author:
Md Jamal Uddin, PhD
Research Professor, Graduate School of Pharmaceutical Sciences, College of Pharmacy,
Ewha Womans University, Seoul 03760, Republic of Korea,
Phone: +821086737008, Email:
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative pathogen of
deadly Coronavirus disease-19 (COVID-19) pandemic, which emerged as a major threat to public
health across the world. Although there is no clear gender or socioeconomic discrimination in the
incidence of COVID-19, individuals who are older adults and/or with comorbidities and
compromised immunity have a relatively higher risk of contracting this disease. Since no specific
drug has yet been discovered, strengthening immunity along with maintaining a healthy living is
the best way to survive this disease. As a healthy practice, calorie restriction in the form of
intermittent fasting in several clinical settings has been reported to promote several health benefits,
including priming of the immune response. This dietary practice also activates autophagy, a cell
surveillance system that boosts up immunity. With these prevailing significance in priming host
defense, intermittent fasting could be a potential strategy amid this outbreak to fighting off SARS-
CoV-2 infection. Currently, no review so far available proposing intermittent fasting as an
encouraging strategy in the prevention of COVID-19. A comprehensive review has therefore been
planned to highlight the beneficial role of fasting in immunity and autophagy, that underlie the
possible defense against SARS-CoV-2 infection. The COVID-19 pathogenesis and its impact on
host immune response have also been briefly outlined. This review aimed at revisiting the
immunomodulatory potential of intermittent fasting that may constitute a promising preventive
strategy against COVID-19.
KEYWORDS: SARS-COV-2, Fasting, Autophagy, Cytokine storm, Immune responses, COVID-
COVID-19, which was first reported in Wuhan, China now emerged as a global pandemic. As of
7 May 2020, there is a total of 3,843,524 confirmed cases of COVID-19, including 265,668 deaths
worldwide [1]. Individuals with coexisting conditions (diabetes, hypertension, chronic bronchitis,
cancer, etc.) [2] and compromised immune systems [3] are particularly vulnerable to this disease.
Although the case fatality rate of the current outbreak (~2%) is lower than that of the previous two
similar outbreaks, SARS (~10%) in 2002-2004 and MERS (~34%) in 2015 [4], the current one
already exceeded the previous two in terms of the rate at which people are infected [1]. The matter
of concern is that although the previous two outbreaks have been successfully contained, no
suitable way has been found yet that can control the current outbreak. As newly emerged, no
suitable therapy against COVID-19 has yet been discovered, nor even a clear concept about the
pathogenesis of this disease. However, as patients with COVID-19 experience similar symptoms
(such as sore throat, persistent high fever, and severe respiratory distress) like the previously
emerged outbreaks, including SARS and MERS [5], the pathogenesis of this disease is more likely
to be similar to that of those coronavirus diseases that involved massive cytokine storm [6, 7].
Moreover, the consensus is that the disease can be fatal if the immune system is already
The immune system plays a critical role in fighting off SARS-CoV-2 infection, however,
deregulated immune response may result in immunopathology and impaired pulmonary function
[7, 8]. Autophagy is a potential cell surveillance system that plays a pivotal role in the regulation
of both innate [9] and adaptive immunity [10]. Induction of autophagy can potentially promote the
immune system [11, 12]. Targeting the immune system as well as the cellular processes (here,
autophagy) that regulate immunity could offer a strategic tool against SARS-CoV-2 infection.
Fasting, a willful abstaining from eating for a certain period of time, is observed as a
religious ritual that has known to have a myriad of health benefits, including boosting up immunity,
resistance to stress, slowing down aging process, and increasing longevity without noticeable side
effects [13, 14]. Fasting also has shown to activate autophagy [15, 16], which in turn promotes
immunity [17]. As the COVID-19 lacks a specific therapy, preventive measures that can prime
host defense could help contain this disease. Considering the regulatory roles of fasting on
autophagy and immunity, we anticipate that fasting may become a possible preventive strategy
against COVID-19. In this review, we revisit the current knowledge of fasting as a possible
important mediator that is involved in the diverse pathophysiological phenomena, including host
immune response, autophagy, and the pathogenesis of SARS-CoV-2 infection. A better
understanding of the physiological impacts of fasting is crucial to propagate a further investigation
on this dietary practice as a novel preventive option against SARS-CoV-2 infection.
SARS-CoV-2 infection shares common pathophysiology with other pathogenic coronaviruses,
including SARS-CoV and MERS-CoV [18]. SARS-CoV-2 infects host cells through binding with
angiotensin converting enzyme 2 (ACE2) receptor which is predominantly expressed in pulmonary
alveolar epithelial cells [19, 20]. Once inside the cell, the virus multiplies by taking over the host
cell machinery and causes damage to the infected cells. SARS-CoV-2 infection and the damaged
pulmonary cells induce a local immune response, that recruits macrophages and monocytes to
respond to the infection [21].
In most cases, the immune response that follows viral infection readily subsides, and
patients ultimately recover. However, in severe cases, patients may experience deadly
consequences, including pneumonia which are associated with dysfunctional immune response,
i.e., massive inflammatory cell infiltration and elevated and persistent levels of pro-inflammatory
cytokines and chemokines (IL-1β, IL-2, IL-6, IL-7, IL-10, GM-CSF, IP-10, MCP-1, and TNFα)
in response of the innate immunity to viral infection [7, 22]. These massive cytokine surges
develop a severe immunopathological condition, termed as “cytokine storm” which, in turn, may
lead to multiple pathological consequences, including extensive pulmonary edema, acute
respiratory distress syndrome (ARDS), and multi-organ failure [7, 23].
Along with innate immunity, the host body that encounters viral infection also develops
the adaptive immune responses recruiting virus-specific T lymphocytes and B lymphocytes,
respectively, to stimulate cell-mediated and humoral immune responses. These immune responses
either potentiate inflammation or neutralize invading viruses. The antigen-presenting cells (APC)
such as macrophages and dendritic cells present the viral antigen to T cells through human
leukocyte antigen (HLA) [3]. Once activated, T cells are transformed into multiple forms,
activating both cell-mediated and humoral immune response [3]. CD8+ T cells directly destroy
virus-infected cells [24], whereas CD4+ T cells are crucial to prime both CD8+ T cells and B cells.
Of the two subsets of CD4+, Th1 cells either activate natural killer cells or CD8+ T cells or may
remain as memory T cells [3]. Whereas, CD4+ Th2 cells stimulate B cells to be converted into
plasma B cells which then generate SARS-CoV-2-specific antibodies (mainly IgM and IgG) [3].
These antibodies, in turn, bind and neutralize SARS-CoV-2. Some of the B cells may form immune
Like many other pathogenic microorganisms, SARS-CoV-2 also evolves mechanisms that
help evade the host immune system. One such strategy is the persistent activation of NLRP3
(NACHT, LRR, and PYD domains-containing protein 3) inflammasome, a component of the
innate immune system that induced caspase-1 activity and pro-inflammatory cytokines such as
interleukin (IL)-1β and IL-18 secretion in macrophages [25]. Although the activation of NLRP3
inflammasome and the subsequent inflammation play crucial roles in the host antiviral immune
responses, the aberrant NLRP3 inflammasome activation or chronic inflammation may also result
in the severe pathological outcomes as was evident in an influenza A virus infection model in
which the experimental animals experienced severe lung injury with an increased level of type I
interferons and persistent NLRP3 inflammasome activation [26]. SARS-CoV infection also
involves persistent activation of NLRP3 inflammasome by open reading frame 3a (ORF3a) [25,
27]. Targeting NLRP3 inflammasome could, therefore, be a promising strategy for restraining viral
infection [28].
Autophagy is a lysosome dependent evolutionarily conserved process that breakdowns and
recycles dysfunctional, lethal and mutant biomolecules, organelles, and invading pathogens to
retain cellular homeostasis [29-31]. In autophagy, autophagosomes, a double membrane vesicles,
engulf and fuse cytoplasmic elements that degraded and recycled the cargo [30, 32] to produce
sugars, nucleosides/nucleotides, amino acids, and fatty acids. These vital components can be
channeled to the other metabolic pathways for cellular utilization [33].
In addition, autophagy is associated with various pathophysiological processes, such as cell
survival, cell death, aging, and immunity [34, 35]. Autophagy is involved in the antigenic
presentation of pathogen (for example, virus) components to the immune system [36, 37].
Autophagy modulates the constituents of immune system, including T and B lymphocytes,
dendritic cells, macrophages, and natural killer (NK) cells [38]. In innate as well as adaptive
immune reactions, autophagy stimulates to maintain survival, homeostasis, proliferation,
activation, as well as differentiation [11]. Besides, autophagy also encourages immune-mediated
cells to release antibodies and cytokines [39]. During innate immunity, autophagy acts as a pattern
of downstream receptors recognition through stimulation of the receptors of innate immunity
containing nod-like receptors and toll-like receptors (TLR7), which triggers effector responses
such as cytokine production, activation of NK T cell, and phagocytosis [40] (Figure 1).
Figure 1. Autophagy-dependent innate immune response. Autophagy may induce innate
immunity by delivering viral nucleic acids to endosomes containing Toll-like receptor 7
(TLR7), which stimulates type 1 interferon (IFN) production.
During adaptive immunity, autophagy is important for antigenic presentation, development
of lymphocyte, selection of thymus, as well as cytokines release and homeostasis [10]. The
adaptive immune reaction is regulated by CD4+ as well as CD8+ T cells [41]. T cell receptors act
together with antigen-presenting cells to promote maturation of antibodies [42]. Autophagy can be
enhanced by antigen presentation, and autophagy activation recruits ATG8/LC3 (autophagy-
related 8/light chain 3) to phagosome membranes enclosed by the receptors of pathogen-associated
molecular pattern that improve phagosomal fusion with lysosomes along with the transformation
of phagosomal content [43]. These events contribute to increasing in antigen presentation and
adaptive immunity.
Autophagy is exclusively important during periods of stress and starvation because of its role in
furnishing cells with nutrients and energy by recycling fuel-rich macromolecules [44]. Autophagy
initiates with the triggering of Unc-51-like kinase (ULK) complex [45] which is regulated by the
mechanistic target of rapamycin (mTOR) that can sense nutrient levels in the environment [46].
Under nutrient-rich conditions, mTOR phosphorylates ULK1/2 leading to the inhibition of
autophagy. On the contrary, mTOR detaches from the ULK complex during periods of fasting or
starvation leading to the activation of autophagy [45]. In addition, AMP-activated protein kinase
negatively regulates mTOR, and also directly activates ULK1 complex, thereby acting as a positive
regulator of autophagy in response to nutrient depletion. Fasting also upregulates several other
autophagy-related proteins such as Atg6, Atg7, Atg8, LC3-II, Beclin1, p62, Sirt1, LAMP2, and
ATG101 and thus potentially modulates autophagy [16].
Autophagy inhibition positively influences viral replication or virulence [47-49]. Many
viruses inhibit autophagy by blocking autophagy-inducing pathways, AKT1/BECN1, for example,
to promote virus replication [49, 50]. A recent study has validated that SARS-CoV-2 infection also
suppressed autophagy [51]. This study also demonstrated that the pharmacological intervention
aimed at autophagy induction showed potentiality against this infection [51]. Similarly,
intermittent fasting that causes nutrient depletion, the most potent known physiological autophagy-
stimulator, can induce autophagy [16, 52]. One study found that in rats that were starved for 24-
46 h, most of the cells in almost every vital tissue had an increased number of autophagosomes
[53]. Autophagy inhibition abrogated the anti-aging effects of fasting, indicating that fasting
mediates autophagy induction [54]. Another study demonstrated that nutrient deprivation
promoted longevity through the Sirtuin-1-dependent induction of autophagy [55]. The beneficial
roles of fasting-mediated autophagy promotion have also been reported in functional homeostasis
of many organs and tissues [16]. In addition to priming the host immune system, fasting-induced
autophagy can improve cellular resistance to stress by increasing the metabolic buffering capacity
of cells and thus preparing the human body to deal with various stresses (Figure 2).
Figure 2. Fasting mediates autophagy. Autophagy receives fasting signals through two
metabolic sensors such as mTOR and AMPK. Under the condition of nutrient depletion,
mTOR detaches from the ULK1 complex leading to the activation of autophagy. Whereas,
AMPK negatively regulates mTOR, and also directly activates ULK1 complex, thereby acting
as a positive regulator of autophagy in response to nutrient depletion. Beclin1 complex is
another autophagy activator that is negatively regulated by mTOR. Once autophagy is initiated,
cytoplasmic elements (cargo) to be recycled are engulfed into double-membrane vesicles,
termed as autophagosomes, which fuse with lysosomes forming autolysosomes, where cargos
are degraded. Autophagy is a multistep process that includes (1) initiation, (2) membrane
nucleation and phagophore formation, (3) phagophore elongation, (4) docking and fusion with
the lysosome, and (5) degradation, which are regulated by autophagy-related proteins (ATGs).
mTOR, mechanistic target of rapamycin; AMPK, AMP-activated protein kinase.
Intermittent fasting (IF) reduces inflammation and thus could offer some promising health benefits
in certain disease conditions such as obesity, asthma, and rheumatoid arthritis, to which
inflammatory response is crucially implicated [56]. Fasting enhanced insulin sensitivity and
promoted cellular stress resistance [57], and thus help evolve resilience in immune response. IF
improved clinical outcomes and caused a reduction of the biomarkers of inflammation (serum
TNFα) and oxidative stress (8-isoprostane, nitrotyrosine, and protein carbonyls) in asthma patients
[58]. IF that practiced in Holy Ramadan (from dawn to sunset for over 14 h daily for 30 consecutive
days) upregulated key regulatory proteins of metabolism, DNA repair, and immune system and
resulted in a serum proteome protective against inflammation and associated lifestyle diseases [59].
The potential molecular mechanism of fasting involves the triggering of adaptive cellular stress
responses, that prime host defense to confront with upcoming severe stress and counteract
pathogenesis [56].
Moreover, the potential immune-evading mechanism of SARS-CoV-2 that involves viral
ORF3a-mediated persistent activation of NLRP3 can also be modulated by IF. During IF,
conventional energy metabolism switches preferably towards fat catabolism with the production
of ketones bodies as instant energy sources [60]. The β-hydroxybutyrate (BHB), a major ketone
body that fuels many vital organs during fasting/starvation [61], may also help mitigate
inflammation by blocking NLRP3 inflammasome overactivation. As evident in experimental
models, BHB reduced the production of IL-1β and IL-18 mediated by NLRP3 inflammasome in
human monocytes and suppressed caspase-1 activation and IL-1β production in the mouse [62].
These findings suggest that the anti-inflammatory effects of caloric restriction may be
mechanistically linked to BHB-mediated inhibition of the NLRP3 inflammasome, and point to the
potential use of interventions, IF as an example, that elevate circulating BHB against NLRP3-
mediated proinflammatory diseases [62].
Since the symptoms of COVID-19 are more severe in those who are already suffering from various
diseases and deficient in immunocompetence, the possible preventive measures are to control
prevailing diseases and to boost up defense systems. As already proposed, intermittent fasting
could be an effective approach that may help prevent SARS-CoV-2 infection. This strategy of
dietary restriction can directly (by activating immune response [63]) or indirectly (by inducing
autophagy [15, 16]) stimulate body surveillance system and boost up immunity, and thus prime
host defense to cope with the confronting stresses. However, there is currently no experimental
evidence that described the impacts of fasting against SARS-CoV-2 infection. Even no review
proposed fasting as a preventive strategy against this disease. With addressing some salient
physiological impacts of fasting on the host defense system, this review presents an insight into
the potential benefits against SARS-CoV-2 infection that could be attained through observing
intermittent fasting (Figure 3). Although the health-promoting potentials of fasting are well-known,
a detailed investigation with an appropriate experimental model is warranted to exploit the
complete benefits of fasting in the prevention of SARS-CoV-2 infection.
Figure 3. Fasting as an intervention tool against SARS-CoV-2 infection. Fasting can prime
the host defense system through activating multiple physiological processes, including
immune responses and autophagy. In case of immune responses, the pulmonary alveolar
epithelial cells that are infected with SARS-CoV-2 release damage-associated molecular
patterns (DAMPs) such as nucleic acids, which are recognized by adjacent epithelial cells and
resident macrophages, triggering the release of pro-inflammatory cytokines and chemokines
(IL-6, IP-10, MIP1α, and MCP1). These mediators attract inflammatory cells, including
macrophages, monocytes, and T cells to the site of infection, promoting further inflammation.
In the dysfunctional immune response, there is a massive infiltration of inflammatory cells and
further accumulation of pro-inflammatory mediators (IL-1β, IL-2, IL-6, IL-7, IL-10, G-CSF,
IP-10, MCP-1, and TNFα), leading to an immunopathological condition, referred to as
‘cytokine storm’ that causes multi-organ failure. On the contrary, in protective immune
response, the antigen-presenting cells (macrophages and dendritic cells) present viral antigens
to T cells which stimulate both cell-mediated and humoral immunity. CD8+ T cells kill virus-
infected cells. Of the two subsets of CD4+, Th1 cells either activate natural killer cells or
CD8+ T cells or may remain as memory T cells. Whereas, upon stimulation from CD4+ Th2
cells, B cells are converted into plasma B cells which generate SARS-CoV-2-specific
antibodies that neutralize viruses. Another fasting-mediated cellular process is autophagy that
either degrades viral particles (xenophagy) or activates innate and adaptive immunity. MIP1α,
macrophage inflammatory protein 1α; MCP-1, monocyte chemoattractant protein 1; IP-10,
interferon-γ-inducible protein 10; G-CSF, Granulocyte-macrophage colony-stimulating factor.
While intermittent fasting is in practice in various religions and some of them have been
proven to have potential health benefits, an appropriate fasting plan can also be adjusted on an
individual basis. Along with observing intermittent fasting, other health-benefiting practices such
as exercise and meditation that help improve immunity are also highly recommended. Besides, a
healthy diet enriched with functional ingredients that possess strong antioxidant, anti-
inflammatory, and immunomodulatory properties should always be incorporated in the dietary
chart. During fasting, care should be taken to ensure an adequate amount of essential
micronutrients such as vitamin C, vitamin D, and zinc that help boost up the immunity and anti-
stress mechanisms.
This work acknowledges the RP-Grant 2020 of Ewha Womans University, Republic of Korea.
MAH, MAR, and MSR are grateful to the National Research Foundation of Korea (NRF) for Korea
Research Fellowship (KRF) (#2018H1D3A1A01074712, #2017H1D3A1A02013844 and
#2016H1D3A1908615, respectively) funded by the Ministry of Science and ICT, Republic of
No conflict of interest from authors regarding the publication of this manuscript.
This work was a collaboration among all the authors. MAH and MJU designed outlines and drafted
the manuscript. MAR, MSR, AAMS, RD, KSC, MF, and MJU wrote the initial draft of the
manuscript. MJU proposed the original idea and reviewed the scientific contents described in the
manuscript. All authors read and approved the final submitted version of the manuscript.
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... The beneficial role of RIF and other types of IF in fighting infections and boosting immunity has been reported elsewhere (18)(19)(20). Moreover, Hannan et al. (21) have recently reviewed the importance of IF and how it could be used as a potentially protective approach to fight COVID-19. Furthermore, Faris et al. (22) indicated that RIF positively affects the body's immunity by changing different related elements, including oxidative stress and inflammation, metabolism, body weight, and body composition. ...
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Background: The world is still struggling to control the COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The level of uncertainty regarding the virus is still significantly high. The virus behaves differently in children and young adults. Most children and adolescents are either asymptomatic or have mild symptoms. They generally have a very good prognosis. However, it is not well known whether children and young adults with type 2 diabetes are at risk of getting a severe infection of COVID-19 or not as it has only been reported among adults with diabetes. Many children with type 2 diabetes have been performing dawn to dusk fasting during the month of Ramadan, before and during the COVID-19 pandemic, and the impact of this on their health has not been well investigated. Previous studies with adults have suggested that intermittent fasting may be beneficial in different ways including reversal of type 2 diabetes and prevention of COVID-19 infection. Objective: The primary aim of this narrative review is to summarise the impacts of the COVID-19 pandemic on children and young adults with type 2 diabetes, and to identify the knowledge gaps in the literature. It also explores the importance of intermittent fasting in reversing the pathogenesis of diabetes and highlighting the effects of Ramadan fasting on these patients. Methods: This narrative review has been produced by examining several databases, including Google Scholar, Research Gate, PubMed, Cochrane Library, MEDLINE (EBSCO), and Web of Science. The most common search terms used were “COVID-19 AND Children”, “SARS-CoV-2 AND/OR Children”, “COVID-19 AND Diabetes” “COVID-19 Epidemiology”, “COVID-19 AND Ramadan fasting”, “COVID-19 and Intermittent fasting”. All the resources used are either peer-reviewed articles/reports and/or official websites, such as the BBC and GOV.UK. Results: Having reviewed the currently limited evidence, it has been found that the incidence of COVID-19 among children with type 2 diabetes seems to be not much different from children without diabetes. However, these patients are still vulnerable to any infection. Several studies have reported that prevention programmes such as intermittent fasting are effective to protect these groups of patients from developing any complications. Moreover, observing Ramadan fasting could be beneficial for some children with established diabetes and people at risk. Conclusion: Children and young adults with type 2 diabetes are not at risk of severe COVID-19 infection as the case in adults with diabetes. More research is needed to identify the impact of COVID-19 and to investigate the efficacy and safety of intermittent fasting, including Ramadan fasting, among these age groups. Implementing these cost-effective programmes may have a great impact in minimising the incidence of diabetes among these age groups during the current pandemic.
... Therefore, if human body ought to fight against a deadly virus like SARS-CoV-2, a strong immune system is much needed which involve several immune responses including autophagy 65,88,89 . Fatal viruses like SARS-CoV-2 can decrease the action of autophagy but there are several compound that can induce autophagy to fight against these type of virus so this immune response can be considered as a tool to fight against COVID19 [90][91][92][93][94][95] . ...
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Honey and its various ingredients have been in limelight as an effective natural therapy capable of normalizing the situation by attenuating acute inflammation through encouraging immune response. Several studies have proved its potential healing capability against numerous chronic diseases/conditions, including diabetes, hypertension, autophagy dysfunction, bacterial and fungal infections. More importantly, honey showed its virucidal effect on several enveloped viruses such as HIV, influenza virus, herpes simplex, and varicella zoster virus. Honey can be beneficial for patients with COVID-19 caused by an enveloped virus SARS-CoV-2 through simultaneously boosting the host immune system, improving comorbid conditions and antiviral activities. Moreover, a clinical trial of honey on COVID-19 patients has been undergoing. In this review, we summarized the potential benefits of honey and its ingredients in the context of antimicrobial activities, numerous chronic diseases, and host immune system and thereby tried to establish a relationship with honey for the treatment of COVID-19. This review will be helpful to reconsider the insights into the potential therapeutic effects of honey in the context of COVID-19 pandemic. However, the effects of honey on SARS-CoV-2 replication and/or host immune system need to be further investigated by in vitro and in vivo studies.
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The outbreak of Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), has thus far killed over 3,000 people and infected over 80,000 in China and elsewhere in the world, resulting in catastrophe for humans. Similar to its homologous virus, SARS-CoV, which caused SARS in thousands of people in 2003, SARS-CoV-2 might also be transmitted from the bats and causes similar symptoms through a similar mechanism. However, COVID-19 has lower severity and mortality than SARS but is much more transmissive and affects more elderly individuals than youth and more men than women. In response to the rapidly increasing number of publications on the emerging disease, this article attempts to provide a timely and comprehensive review of the swiftly developing research subject. We will cover the basics about the epidemiology, etiology, virology, diagnosis, treatment, prognosis, and prevention of the disease. Although many questions still require answers, we hope that this review helps in the understanding and eradication of the threatening disease.
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Currently there is no effective antiviral therapy for SARS-CoV-2 infection, which frequently leads to fatal inflammatory responses and acute lung injury. Here, we discuss the various mechanisms of SARS-CoV-mediated inflammation. We also assume that SARS-CoV-2 likely shares similar inflammatory responses. Potential therapeutic tools to reduce SARS-CoV-2-induced inflammatory responses include various methods to block FcR activation. In the absence of a proven clinical FcR blocker, the use of intravenous immunoglobulin to block FcR activation may be a viable option for the urgent treatment of pulmonary inflammation to prevent severe lung injury. Such treatment may also be combined with systemic anti-inflammatory drugs or corticosteroids. However, these strategies, as proposed here, remain to be clinically tested for effectiveness.
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Murine studies showed that disruption of circadian clock rhythmicity could lead to cancer and metabolic syndrome. Time-restricted feeding can reset the disrupted clock rhythm, protect against cancer and metabolic syndrome. Based on these observations, we hypothesized that intermittent fasting for several consecutive days without calorie restriction in humans would induce an anticarcinogenic proteome and the key regulatory proteins of glucose and lipid metabolism. Fourteen healthy subjects fasted from dawn to sunset for over 14 h daily. Fasting duration was 30 consecutive days. Serum samples were collected before 30-day intermittent fasting, at the end of 4th week during 30-day intermittent fasting, and one week after 30-day intermittent fasting. An untargeted serum proteomic profiling was performed using ultra high-performance liquid chromatography/tandem mass spectrometry. Our results showed that 30-day intermittent fasting was associated with an anticancer serum proteomic signature, upregulated key regulatory proteins of glucose and lipid metabolism, circadian clock, DNA repair, cytoskeleton remodeling, immune system, and cognitive function, and resulted in a serum proteome protective against cancer, metabolic syndrome, inflammation, Alzheimer's disease, and several neuropsychiatric disorders. These findings suggest that fasting from dawn to sunset for 30 consecutive days can be preventive and adjunct therapy in cancer, metabolic syndrome, and several cognitive and neuropsychiatric diseases. Significance Our study has important clinical implications. Our results showed that intermittent fasting from dawn to sunset for over 14 h daily for 30 consecutive days was associated with an anticancer serum proteomic signature and upregulated key regulatory proteins of glucose and lipid metabolism, insulin signaling, circadian clock, DNA repair, cytoskeleton remodeling, immune system, and cognitive function, and resulted in a serum proteome protective against cancer, obesity, diabetes, metabolic syndrome, inflammation, Alzheimer's disease, and several neuropsychiatric disorders. Importantly, these findings occurred in the absence of any calorie restriction and significant weight loss. These findings suggest that intermittent fasting from dawn to sunset can be a preventive and adjunct therapy in cancer, metabolic syndrome and Alzheimer's disease and several neuropsychiatric diseases.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Alongside investigations into the virology of SARS-CoV-2, understanding the fundamental physiological and immunological processes underlying the clinical manifestations of COVID-19 is vital for the identification and rational design of effective therapies. Here, we provide an overview of the pathophysiology of SARS-CoV-2 infection. We describe the interaction of SARS-CoV-2 with the immune system and the subsequent contribution of dysfunctional immune responses to disease progression. From nascent reports describing SARS-CoV-2, we make inferences on the basis of the parallel pathophysiological and immunological features of the other human coronaviruses targeting the lower respiratory tract — severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Finally, we highlight the implications of these approaches for potential therapeutic interventions that target viral infection and/or immunoregulation. In the short time since SARS-CoV-2 infections emerged in humans, much has been learned about the immunological processes that underlie the clinical manifestation of COVID-19. Here, the authors provide an overview of the pathophysiology of SARS-CoV-2 infection and discuss potential therapeutic approaches.
SARS-CoV-2 virus, the causative agent of the coronavirus infectious disease-19 (COVID-19), is taking the globe by storm, approaching 500,000 confirmed cases and over 21,000 deaths as of March 25, 2020. While under control in some affected Asian countries (Taiwan, Singapore, Vietnam), the virus demonstrated an exponential phase of infectivity in several large countries (China in late January and February and many European countries and the USA in March), with cases exploding by 30–50,000/day in the third and fourth weeks of March, 2020. SARS-CoV-2 has proven to be particularly deadly to older adults and those with certain underlying medical conditions, many of whom are of advanced age. Here, we briefly review the virus, its structure and evolution, epidemiology and pathogenesis, immunogenicity and immune, and clinical response in older adults, using available knowledge on SARS-CoV-2 and its highly pathogenic relatives MERS-CoV and SARS-CoV-1. We conclude by discussing clinical and basic science approaches to protect older adults against this disease.
Background The 2019 novel coronavirus (SARS-CoV-2) is a new human coronavirus which is spreading with epidemic features in China and other Asian countries with cases reported worldwide. This novel Coronavirus Disease (COVID-19) is associated with a respiratory illness that may cause severe pneumonia and acute respiratory distress syndrome (ARDS). Although related to the Severe Acute Respiratory Syndrome (SARS) and the Middle East Respiratory Syndrome (MERS), COVID-19 shows some peculiar pathogenetic, epidemiological and clinical features which have not been completely understood to date. Objectives We provide a review of the differences in terms of pathogenesis, epidemiology and clinical features between COVID-19, SARS and MERS. Sources The most recent literature in English language regarding COVID-19 has been reviewed and extracted data have been compared with the current scientific evidence about SARS and MERS epidemics. Content COVID-19 seems not to be very different from SARS regarding its clinical features. However, it has a fatality rate of 2.3%, lower than SARS (9.5%) and much lower than MERS (34.4%). It cannot be excluded that because of the COVID-19 less severe clinical picture it can spread in the community more easily than MERS and SARS. The actual basic reproductive number (R0) of COVID-19 (2-2.5) is still controversial. It is probably slightly higher than the R0 of SARS (1.7-1.9) and higher than MERS (<1),. The gastrointestinal route of transmission of SARS-CoV-2, which has been also assumed for SARS-CoV and MERS-CoV, cannot be ruled out and needs to be further investigated. Implications There is still much more to know about COVID-19, especially as concerns mortality and capacity of spreading on a pandemic level. Nonetheless, all of the lessons we learned in the past from SARS and MERS epidemics are the best cultural weapons to face this new global threat.
The NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome is an oligomeric complex comprised of the NOD-like receptor NLRP3, the adaptor ASC, and caspase-1. This complex is crucial to the host's defense against microbes as it promotes IL-1β and IL-18 secretion and induces pyroptosis. NLRP3 recognizes variety of pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) generated during viral replication that triggers the NLRP3 inflammasome-dependent antiviral immune responses and facilitates viral eradication. Meanwhile, several viruses have evolved elaborate strategies to evade the immune system by targeting the NLRP3 inflammasome. In this review, we will focus on the crosstalk between the NLRP3 inflammasome and viruses, provide an overview of viral infection-induced NLRP3 inflammasome activation, and the immune escape strategies of viruses through their modulation of the NLRP3 inflammasome activity.
Severe acute respiratory syndrome coronavirus (SARS-CoV) is capable of inducing a storm of proinflammatory cytokines. In this study, we show that the SARS-CoV open reading frame 3a (ORF3a) accessory protein activates the NLRP3 inflammasome by promoting TNF receptor-associated factor 3 (TRAF3)-mediated ubiquitination of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC). SARS-CoV and its ORF3a protein were found to be potent activators of pro-IL-1β gene transcription and protein maturation, the 2 signals required for activation of the NLRP3 inflammasome. ORF3a induced pro-IL-1β transcription through activation of NF-κB, which was mediated by TRAF3-dependent ubiquitination and processing of p105. ORF3a-induced elevation of IL-1β secretion was independent of its ion channel activity or absent in melanoma 2 but required NLRP3, ASC, and TRAF3. ORF3a interacted with TRAF3 and ASC, colocalized with them in discrete punctate structures in the cytoplasm, and facilitated ASC speck formation. TRAF3-dependent K63-linked ubiquitination of ASC was more pronounced in SARS-CoV-infected cells or when ORF3a was expressed. Taken together, our findings reveal a new mechanism by which SARS-CoV ORF3a protein activates NF-κB and the NLRP3 inflammasome by promoting TRAF3-dependent ubiquitination of p105 and ASC.-Siu, K.-L., Yuen, K.-S., Castaño-Rodriguez, C., Ye, Z.-W., Yeung, M.-L., Fung, S.-Y., Yuan, S., Chan, C.-P., Yuen, K.-Y., Enjuanes, L., Jin, D.-Y. Severe acute respiratory syndrome coronavirus ORF3a protein activates the NLRP3 inflammasome by promoting TRAF3-dependent ubiquitination of ASC.
Autophagy is a lysosomal degradation process and protective housekeeping mechanism to eliminate damaged organelles, long-lived misfolded proteins and invading pathogens. Autophagy functions to recycle building blocks and energy for cellular renovation and homeostasis, allowing cells to adapt to stress. Modulation of autophagy is a potential therapeutic target for a diverse range of diseases, including metabolic conditions, neurodegenerative diseases, cancers and infectious diseases. Traditionally, food deprivation and calorie restriction (CR) have been considered to slow aging and increase longevity. Since autophagy inhibition attenuates the anti-aging effects of CR, it has been proposed that autophagy plays a substantive role in CR-mediated longevity. Among several stress stimuli inducers of autophagy, fasting and CR are the most potent non-genetic autophagy stimulators, and lack the undesirable side effects associated with alternative interventions. Despite the importance of autophagy, the evidence connecting fasting or CR with autophagy promotion has not previously been reviewed. Therefore, our objective was to weigh the evidence relating the effect of CR or fasting on autophagy promotion. We conclude that both fasting and CR have a role in the upregulation of autophagy, the evidence overwhelmingly suggesting that autophagy is induced in a wide variety of tissues and organs in response to food deprivation.