The role of iron in the pathogenesis of COVID-19 and possible treatment with lactoferrin and other iron chelators

Habib, Hosam M.; Ibrahim, Sahar; Zaim, Aamnah; Ibrahim, Wissam H.

doi:10.1016/j.biopha.2021.111228

Cited by 202 publications

(222 citation statements)

References 115 publications

(164 reference statements)

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“…The immunomodulatory action is an important functional feature of LF, which can not only modulate the immune system through connecting both adaptive and innate immune responses but also maintain the homeostasis of the host in several human diseases, from microbial infection to cancer development (Eipper et al, 2016;Habib et al, 2021;Uversky et al, 2017). It has a comparable ability to lower inflammation and positively modulate the changes associated with iron metabolism, including trafficking and storage of iron, which attributes to restoring T conventional lymphocytes (T conv ) responses (Habib et al, 2021;Macciò & Madeddu, 2020).…”

Section: Host Immune System Modulation Action Of Lactoferrinmentioning

confidence: 99%

“…Although many functions of LF are dependent on its ability to chelate two ferric ions as well as bind anionic moieties, the multifunctionality of this protein is not entirely determined by its chelation potential, and LF is known to act as a potent anti-inflammatory and immunomodulatory molecule (Habib et al, 2021). Its anti-inflammatory activity is defined by its ability to enter the host cell via the specific receptor, followed by the translocation from the cytoplasm into the host cell nucleus.…”

Section: Host Immune System Modulation Action Of Lactoferrinmentioning

confidence: 99%

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Natural resources to control COVID-19: could lactoferrin amend SARS-CoV-2 infectivity?

Mattar

Elrashdy

Almehdar

et al. 2021

PeerJ

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The world population is still facing the second wave of the COVID-19 pandemic. Such a challenge requires complicated tools to control, namely vaccines, effective cures, and complementary agents. Here we present one candidate for the role of an effective cure and/or complementary agent: lactoferrin. It is the cross-talking mediator between many organs/cellular systems in the body. It serves as a physiological, immunological, and anti-microbial barrier, and acts as a regulator molecule. Furthermore, lactoferrin has receptors on most tissues cells, and is a rich source for bioactive peptides, particularly in the digestive system. In the past months, in vitro and in vivo evidence has accumulated regarding lactoferrin’s ability to control SARS-CoV-2 infectivity in different indicated scenarios. Also, lactoferrin or whey milk (of human or other mammal’s origin) is a cheap, easily available, and safe agent, the use of which can produce promising results. Pharmaceutical and/or food supplementary formulas of lactoferrin could be particularly effective in controlling the gastrointestinal COVID-19-associated symptoms and could limit the fecal-oral viral infection transmission, through mechanisms that mimic that of norovirus infection control by lactoferrin via induction of intestinal innate immunity. This natural avenue may be effective not only in symptomatic patients, but could also be more helpful in asymptomatic patients as a main or adjuvant treatment.

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Section: Host Immune System Modulation Action Of Lactoferrinmentioning

confidence: 99%

Section: Host Immune System Modulation Action Of Lactoferrinmentioning

confidence: 99%

Natural resources to control COVID-19: could lactoferrin amend SARS-CoV-2 infectivity?

Mattar

Elrashdy

Almehdar

et al. 2021

PeerJ

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“…The presence of lactoferrin itself and its anti-inflammatory properties perfectly harmonize with anti-viral activities. The important role of lactoferrin is to calm down the cytokine storm, which is the main cause of the rapid course of COVID-19 [ 45 , 46 , 47 , 48 , 49 , 50 , 57 , 79 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 ]. It can be also used to treat osteoporosis because it reduces osteolysis—the destruction of bone cells [ 134 ].…”

Section: Discussionmentioning

confidence: 99%

“…In the adjuvant treatment of metronidazole in women with recurrent bacterial vaginosis BV, preparations containing a probiotic mixture containing Lactobacillus acidophilus GLA-14 and Lactobacillus rhamnosus HN001 in combination with bovine lactoferrin were used [ 116 ]. It is increasingly recognized that iron overload contributes to the pathogenesis of viral infection [ 117 , 118 ]. Indeed, several of the symptoms of COVID-19, which include inflammation, hypercoagulation, hyperferritinemia and immune dysfunction, are similar to the symptoms of iron overload [ 117 , 118 ].…”

Section: Discussionmentioning

confidence: 99%

“…It is increasingly recognized that iron overload contributes to the pathogenesis of viral infection [ 117 , 118 ]. Indeed, several of the symptoms of COVID-19, which include inflammation, hypercoagulation, hyperferritinemia and immune dysfunction, are similar to the symptoms of iron overload [ 117 , 118 ]. Iron is highly chemically reactive and potentially toxic due to damage to cellular components, such as lipids (ferroptosis), nucleic acids and cellular proteins, leading to the activation of acute and chronic inflammation.…”

Section: Discussionmentioning

confidence: 99%

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Protective Action of L. salivarius SGL03 and Lactoferrin against COVID-19 Infections in Human Nasopharynx

Kucia¹,

Wietrak²,

Szymczak

et al. 2021

Materials

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In this study, we used live viral particles from oral secretions from 17 people infected with SARS-CoV-2 and from 17 healthy volunteers, which were plated on a suitable medium complete for all microorganisms and minimal for L. salivarius growth. Both types of media also contained an appropriately prepared vector system pGEM-5Zf (+) based on the lactose operon (beta-galactosidase system). Incubation was carried out on both types of media for 24 h with the addition of 200 μL of Salistat SGL03 solution in order to test its inhibitory effect on the coronavirus contained in the oral mucosa and nasopharynx, visible as light blue virus particles on the test plates, which gradually disappeared in the material collected from infected persons over time. Regardless of the conducted experiments, swabs were additionally taken from the nasopharynx of infected and healthy people after rinsing the throat and oral mucosa with Salistat SGL03. In both types of experiments, after 24 h of incubation on appropriate media with biological material, we did not find any virus particles. Results were also confirmed by MIC and MBC tests. Results prove that lactoferrin, as one of the ingredients of the preparation, is probably a factor that blocks the attachment of virus particles to the host cells, determining its anti-viral properties. The conducted preliminary experiments constitute a very promising model for further research on the anti-viral properties of the ingredients contained in the Salistat SGL03 dietary supplement.

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COVID‐19‐associated liver injury: Adding fuel to the flame

Wang,

Shen,

et al. 2023

Cell Biochemistry & Function

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COVID‐19 is mainly characterized by respiratory disorders and progresses to multiple organ involvement in severe cases. With expansion of COVID‐19 and SARS‐CoV‐2 research, correlative liver injury has been revealed. It is speculated that COVID‐19 patients exhibited abnormal liver function, as previously observed in the SARS and MERS pandemics. Furthermore, patients with underlying diseases such as chronic liver disease are more susceptible to SARS‐CoV‐2 and indicate a poor prognosis accompanied by respiratory symptoms, systemic inflammation, or metabolic diseases. Therefore, COVID‐19 has the potential to impair liver function, while individuals with preexisting liver disease suffer from much worse infected conditions. COVID‐19 related liver injury may be owing to direct cytopathic effect, immune dysfunction, gut−liver axis interaction, and inappropriate medication use. However, discussions on these issues are infancy. Expanding research have revealed that angiotensin converting enzyme 2 (ACE2) expression mediated the combination of virus and target cells, iron metabolism participated in the virus life cycle and the fate of target cells, and amino acid metabolism regulated immune response in the host cells, which are all closely related to liver health. Further exploration holds great significance in elucidating the pathogenesis, facilitating drug development, and advancing clinical treatment of COVID‐19‐related liver injury. This article provides a review of the clinical and laboratory hepatic characteristics in COVID‐19 patients, describes the etiology and impact of liver injury, and discusses potential pathophysiological mechanisms.

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The role of iron in the pathogenesis of COVID-19 and possible treatment with lactoferrin and other iron chelators

Cited by 202 publications

References 115 publications

Natural resources to control COVID-19: could lactoferrin amend SARS-CoV-2 infectivity?

Natural resources to control COVID-19: could lactoferrin amend SARS-CoV-2 infectivity?

Protective Action of L. salivarius SGL03 and Lactoferrin against COVID-19 Infections in Human Nasopharynx

COVID‐19‐associated liver injury: Adding fuel to the flame

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