Dietary supplements for the management of COVID-19 symptoms

Summary SARS-CoV-2, the etiological agent of COVID-19, caused a pandemic in 2020, which is only recently slowing down. The symptoms of COVID-19 range from cough to fever and pneumonia and may persist beyond the active state of the infection, in a condition called post-COVID syndrome. The aim of this paper is to review the relationship between COVID-19 and nutrition and to discuss to most up-to-date dietary supplements proposed for COVID-19 treatment and prevention. Nutrition and nutritional dysregulations, such as obesity and malnutrition, are prominent risk factors for severe COVID-19. These factors exert anti-inflammatory and proinflammatory effects on the immune system, thus exacerbating or reducing the immunological response against the virus. As for the nutritional habits, the Western diet induces a chronic inflammatory state, whereas the Mediterranean diet exerts anti-inflammatory effects and has been proposed for ameliorating COVID-19 evolution and symptoms. Several vaccines have been researched and commercialized for COVID-19 prevention, whereas several drugs, although clinically tested, have not shown promising effects. To compensate for the lack of treatment, several supplements have been recommended for preventing or ameliorating COVID-19 symptoms. Thus, it is critical to review the dietary supplements proposed for COVID-19 treatment. Supplements containing α-cyclodextrin and hydroxytyrosol exhibited promising effects in several clinical trials and reduced the severity of the outcomes and the duration of the infection. Moreover, a supplement containing hydroxytyrosol, acetyl L-carnitine, and vitamins B, C, and D improved the symptoms of patients with post-COVID syndrome.

COVID-19 vaccine candidates and vaccine development platforms available worldwide.

The pandemic caused by the worldwide spread of the coronavirus, which first appeared in 2019, has been named coronavirus disease 19 (COVID-19). More than 4.5 million deaths have been recorded due to the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), according to the World Health Organization. COVID-19 Dashboard in September 2021. Apart from the wildtype, other variations have been successfully transmitted early in the outbreak although they were not discovered until March 2020. Modifications in the SARS-CoV-2 genetic material, such as mutation and recombination, have the ability to modify the viral life span, along with transitivity, cellular tropism, and symptom severity. Several processes are involved in introducing novel vaccines to the population, including vaccine manufacturing, preclinical studies, Food and Drug Administration permission or certification, processing, and marketing. COVID-19 vaccine candidates have been developed by a number of public and private groups employing a variety of strategies, such as RNA, DNA, protein, and viral vectored vaccines. This comprehensive review, which included the most subsequent evidence on unique features of SARS-CoV-2 and the associated morbidity and mortality, was carried out using a systematic search of recent online databases in order to generate useful knowledge about the COVID-19 updated versions and their consequences on the disease symptoms and vaccine development.

Inositol and vitamin D may naturally protect human reproduction and women undergoing assisted reproduction from Covid-19 risk.

In late 2019, the new Coronavirus has been identified in the city of Wuhan then COVID-19 spreads like wildfire in the rest of the world. Pregnant women represent a risk category for increased abortion rates and vertical transmission with adverse events on the newborns has been recently confirmed. The scientific world is struggling for finding an effective cure for counteracting symptomatology. Today, there are many therapeutic proposes but none of them can effectively counteract the infection. Moreover, many of these compounds show important side effects not justifying their use. Scientific literature reports an immune system over-reaction through interleukins-6 activation. In this regard, the possibility to control the immune system represents a possible strategy for counteracting the onset of COVID-19 symptomatology. Vitamin D deficiency shows increased susceptibility to acute viral respiratory infections. Moreover, Vitamin D seems involved in host protection from different virus species by modulating activation and release of cytokines. Myo-inositol down-regulates the expression of IL-6 by phosphatidyl-inositol-3-kinase (PI3K) pathway. Furthermore, myo-inositol is the precursor of phospholipids in the surfactant and it is applied for inducing surfactant synthesis in infants for treating respiratory distress syndrome (RDS). This review aims to summarize the evidence about COVID-19 infection in pregnant women and to encourage the scientific community to investigate the use of Vitamin D and Myo-inositol which could represent a possible preventive treatment for pregnant women or women undergoing assisted reproductive technologies (ART).

A pilot study on the preventative potential of alpha-cyclodextrin and hydroxytyrosol against SARS-CoV-2 transmission.

BACKGROUND AND AIM OF THE WORK: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current pandemics. This virus attacks the cells by binding to the transmembrane angiotensin I converting enzyme 2. In this study, we experimented a food supplement containing alpha-cyclodextrin and hydroxytyrosol for the improvement of the defenses against the SARS-CoV-2. Hydroxytyrosol has anti-viral properties and is able to reduce the serum lipids in mice. α-cyclodextrin has the ability to deplete sphingolipids and phospholipids from the cellular membranes. The aim of the present preliminary open non-controlled interventional study was to evaluate the efficacy of alpha-cyclodextrin and hydroxytyrosol in improving defenses against SARS-CoV-2. METHODS: Fifty healthy volunteers at a higher risk of SARS-CoV-2 infection from Northern Cyprus and six positive individuals for SARS-CoV-2 were enrolled in this study. The in silico prediction was performed using D3DOCKING to evaluate the interactions of hydroxytyrosol and alpha-cyclodextrin with proteins involved in the SARS-CoV-2 endocytosis. RESULTS: The 50 volunteers did not become positive in 15 days for SARS-CoV-2 after the administration of the compound for two weeks, despite they were at higher risk of infection than the general population. Interestingly, in the cohort of six positive patients, two patients were administered the spray and became negative after five days, despite the viral load was higher in the treated subjects than the untreated patients who became negative after ten days. In addition, we identified possible interactions among hydroxytyrosol and alpha-cyclodextrin with the protein Spike and the human proteins ACE2 and TMPRSS2. CONCLUSIONS: We reported on the results of the possible role of alpha-cyclodextrin and hydroxytyrosol in improving defenses against SARS-CoV-2. The next step will be the administration of the compound to a larger cohort in a controlled study to confirm the reduction of the infection rate of SARS-CoV-2 in the treated subjects.

Pilot study for the evaluation of safety profile of a potential inhibitor of SARS-CoV-2 endocytosis.

BACKGROUND AND AIM OF THE WORK: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current pandemics of coronavirus disease. This virus is able to attack the cells of the airway epithelium by binding to the transmembrane angiotensin I converting enzyme 2 (ACE2). We developed an oral spray that could inhibit the SARS-CoV-2 endocytosis. The spray contains hydroxytyrosol for its anti-viral, anti-inflammatory and anti-oxidant properties, and α-cyclodextrin for its ability to deplete sphingolipids, that form the lipid rafts where ACE2 localizes. The aim of the present pilot multi-centric open non-controlled observational study was to evaluate the safety profile of the "Endovir Stop" spray. METHODS: An MTT test was performed to evaluate cytotoxicity of the spray in two human cell lines. An oxygen radical absorbance capacity assay was performed to evaluate the antioxidant capacity of the spray. The spray was also tested on 87 healthy subjects on a voluntary basis. RESULTS: The MTT test revealed that the spray is not cytotoxic. The ORAC assay showed a good antioxidant capacity for the spray. Endovir Stop tested on healthy volunteers showed the total absence of side effects and drug interactions during the treatment. CONCLUSIONS: We demonstrated that Endovir Stop spray is safe. The next step would be the administration of the efficacy of the spray by testing it to a wider range of people and see whether there is a reduced infection rate of SARS-CoV-2 in the treated subjects than in the non-treated individuals.

Natural compounds as inhibitors of SARS-CoV-2 endocytosis: A promising approach against COVID-19.

BACKGROUND AND AIM: The recent COVID-19 pandemic caused by SARS-CoV-2 affected more than six million people and caused thousands of deaths. The lack of effective drugs or vaccines against SARS-CoV-2 further worsened the situation. This review is focused on the identification of molecules that may inhibit viral entry into host cells by endocytosis. METHODS: We performed the literature search for these natural compounds in the articles indexed in PubMed. RESULTS: Natural products against viral infections have been gaining importance in recent years. Specific natural compounds like phytosterols, polyphenols, flavonoids, citrus, galangal, curcuma and hydroxytyrosol are being analyzed to understand whether they could inhibit SARS-CoV-2. CONCLUSIONS: We reviewed natural compounds with potential antiviral activity against SARS-CoV-2 that could be used as a treatment for COVID-19.

Natural small molecules as inhibitors of coronavirus lipid-dependent attachment to host cells: a possible strategy for reducing SARS-COV-2 infectivity?

BACKGROUND: Viral infectivity depends on interactions between components of the host cell plasma membrane and the virus envelope. Here we review strategies that could help stem the advance of the SARS-COV-2 epidemic. METHODS AND RESULTS: We focus on the role of lipid structures, such as lipid rafts and cholesterol, involved in the process, mediated by endocytosis, by which viruses attach to and infect cells. Previous studies have shown that many naturally derived substances, such as cyclodextrin and sterols, could reduce the infectivity of many types of viruses, including the coronavirus family, through interference with lipid-dependent attachment to human host cells. CONCLUSIONS: Certain molecules prove able to reduce the infectivity of some coronaviruses, possibly by inhibiting viral lipid-dependent attachment to host cells. More research into these molecules and methods would be worthwhile as it could provide insights the mechanism of transmission of SARS-COV-2 and, into how they could become a basis for new antiviral strategies.