SCIENCE & RESEARCH

Zinc is a relatively inexpensive mineral nutrient that is an effective prophylactic agent to prevent and mitigate the potentially deadly symptomatic SARS-CoV-2 infection.

Increasing the intracellular Zn^2+^ concentration with zinc-ionophores like pyrithione (PT) can efficiently impair the replication of a variety of RNA viruses, including poliovirus and influenza virus.

As of 9 June 2020, indirect evidence from other types of viral respiratory infections suggests that zinc may potentially reduce the risk, duration and severity of SARS-CoV-2 infections; particularly for populations at risk of zinc deficiency. Notably, people with chronic disease co-morbidities and older adults are at risk of lower zinc status. Pending the results of SARS-CoV-2 clinical trials, clinicians might consider assessing zinc status as part of a SARS-CoV-2 clinical work-up to determine if short-term zinc supplementation, either orally or intravenously is indicated for those with low or borderline low results, low dietary intake and/or increased needs.

Currently, indirect evidence suggests zinc may potentially reduce the risk, duration and severity of SARS-CoV-2 infections, particularly for populations at risk of zinc deficiency including people with chronic disease co-morbidities and older adults.

As zinc is essential to preserve natural tissue barriers such as the respiratory epithelium, preventing pathogen entry, for a balanced function of the immune system and the redox system, zinc deficiency can probably be added to the factors predisposing individuals to infection and detrimental progression of COVID-19. Finally, due to its direct antiviral properties, it can be assumed that zinc administration is beneficial for most of the population, especially those with suboptimal zinc status.

Zinc deficiency may be common and associated with severe infection by helping to enhance the interferon type 1 response to the virus and participates in many regulatory pathways.

Role of zinc Zn^+2^ mediates numerous non-specific and specific immunological functions:^16,17^ From normal development and function of cells,^18,19^ including those regulating nonspecific immunity, inter alia, activity of natural killer (NK) cells and neutrophils, and macrophage function; to maintaining expression of tight-junction proteins between lung-lining muco-epithelial cells, blocking entry of pathogens; from increasing cilia length and ciliary beat-frequency in those cells’ mechanical clearance of surface “litter” such as virus particles, and repair of such function in coronavirus-damaged lung cells; to immune response modulation,^21,22^ tamping down on overshooting inflammatory immune responses^22^ (thus preventing, for example, high levels of inflammatory mediators such as destructive reactive oxygen and nitrogen species) and normalizing the ratios of diverse immune cell types.

In vitro replication of influenza (PR/8/34) is significantly inhibited by the addition of the zinc ionophore pyrrolidine dithiocarbamate (110), perhaps through inhibition of the RNA-dependent RNA polymerase (RdRp), as had been suggested 30 y earlier (111). In similar fashion, severe acute respiratory syndrome (SARS) coronavirus RdRp template binding and elongation was inhibited by zinc in Vero-E6 cells (60). Moreover, zinc salts were shown to inhibit respiratory syncytial virus, even while zinc was incubated with HEp-2 cells only before infection, and then removed (72).

Pre-clinical studies have highlighted the antiviral activities of epigallocatechin-3-gallate (EGCG), a catechin primarily found in green tea, against various viruses, including SARS-CoV-2. In this review, we summarize this experimental evidence and highlight the potential use of EGCG as an alternative therapeutic choice for the treatment of SARS-CoV-2 infection.

Conclusions

EGCG, as the major secondary metabolite polyphenol in Camellia sinensis, has been confirmed to be a multifunctional bioactive molecule with potential for anti-infective, anti-proliferation and antiviral effects. In this review, the antiviral effects of EGCG on DNA, RNA, coronaviruses and other viruses were summarized and discussed. EGCG acts antiviral functions in different stages of infection for both nuclear viruses and cytoplasmic viruses, and so is considered to be a potential alternative agent for multiple viral diseases (Table 2).

In the realms of addressing inflammation and how to effectively target SARS-CoV-2 mediated respiratory distress syndrome, we review in this article the available knowledge on the strategic placement of EGCG in curbing inflammatory signals and how it may serve as a broad spectrum therapeutic in asymptomatic and symptomatic COVID-19 patients.

In this report, human coronavirus HCoV-OC43 (beta coronavirus) and HCoV-229E (alpha coronavirus) were used to examine the effect of EGCG on coronavirus. EGCG treatment decreases 3CL-protease activity of HCoV-OC43 and HCoV-229E. Moreover, EGCG treatment decreased HCoV-OC43-induced cytotoxicity. Finally, we found that EGCG treatment decreased the levels of coronavirus RNA and protein in infected cell media. These results indicate that EGCG inhibits coronavirus replication.

We demonstrated that green tea beverage (GTB) or its major ingredient, epigallocatechin gallate (EGCG), were highly effective in inhibiting infection of live SARS-CoV-2 and human coronavirus (HCoV OC43). In addition, infection of the pseudoviruses with spikes of the new variants (UK-B.1.1.7, SA-B.1.351, and CA-B.1.429) was efficiently blocked by GTB or EGCG.

Quercetin Phytosome® (QP), a novel bioavailable form of quercetin, statistically shortens the timing of molecular test conversion from positive to negative, reducing at the same time symptoms severity and negative predictors of COVID-19.

In our study, we found quercetin possessed anti-influenza activity. The subsequent mechanism study indicated quercetin showed inhibitory effect during virus entry. Then we found quercetin interacted with influenza hemagglutinin protein and then inhibited viral-cell fusion.

The focus of this review includes viral pathogenesis as well as the application of quercetin and its derivatives as a complementary therapy in controlling influenza and its related symptoms based on the targets. We also touch on the potential of this class of compounds for treatment of SARS-COV-2, the cause of new pandemic.

Quercetin, as an anti-inflammatory, antioxidant, analgesic and inflammatory compound, is probably a potential treatment for severe inflammation and one of the main life-threatening conditions in patients with COVID-19.

Quercetin has long been evaluated for its potential protective effects against cancers, heart disease, and cells that release histamines.

The agent promotes SIRT2, which then inhibits the NLRP3 inflammasome assembly involved with COVID-19 infection, said Samuel F. Yanuck, DC, of the Program on Integrative Medicine at the University of North Carolina Chapel Hill School of Medicine, who co-authored a review of emerging research on the subject.

In the present study, we investigated the mechanisms and interactions between Quercetin and SARS-CoV-2 targets proteins by using network pharmacology and molecular docking. The renal protective effects of Quercetin on COVID-19-induced AKI may be associated with the blockade of the activation of inflammatory, cell apoptosis-related signaling pathways. Quercetin may also serve as SARS-CoV-2 inhibitor by binding with the active sites of SARS-CoV-2 main protease 3CL and ACE2, therefore suppressing the functions of the proteins to cut the viral life cycle.

This review summarizes the antiviral significance of quercetin and proposes a possible strategy for the effective utilization of natural polyphenols in our daily diet for the prevention of viral infection.

This review focuses on the physicochemical properties, dietary sources, absorption, bioavailability and metabolism of quercetin, especially main effects of quercetin on inflammation and immune function. According to the results obtained both in vitro and in vivo, good perspectives have been opened for quercetin.

Evidence recommends that vitamin D might be a crucial supportive agent for the immune system, mainly in cytokine response regulation against COVID-19. Hence, we carried out a systematic review and meta-analysis in order to maximize the use of everything that exists about the role of vitamin D in the COVID-19.

Vitamin D deficiency has been shown to be associated with worse outcomes of infectious complications, especially in patients admitted to the ICU [8]. The most recognized extra-skeletal action of vitamin D is the regulation of immune function [9]. Vitamin D is an important link between toll-like receptor (TLR) activation, leukocyte accumulation, local inflammation, and antibacterial responses in innate immunity [[10], [11], [12]].

This review discussed the possible roles of vitamin D in reducing the risk of COVID-19 and other acute respiratory tract infections and severity. Moreover, this study determined the correlation of vitamin D levels with COVID-19 cases and deaths in 20 European countries as of 20 May 2020.

In this Viewpoint, we summarize how activation of the vitamin D Receptor (VDR) may be able to decrease acute lung injury (ALI) and Acute Respiratory Distress Syndrome (ARDS).

Despite lower vitamin D receptor levels in rhinovirus-infected epithelial cells, exogenous vitamin D increased antiviral defences most likely via cathelicidin and innate interferon pathways.

A team from the Swiss Faculty of Pharmaceutical Sciences at the University of Basel, led by André Fischer, Manuel Sellner, Santhosh Neranjan, Markus A. Lill, and Martin Smieško, has provided the study development free of charge, which is the most comprehensive screening calculation for SARS to date. A list of 11 compounds was isolated. Taxifolin was among them and, according to the researchers, may also inhibit the main coronavirus protease.

In order to find novel inhibitors, we computationally screened a compound library of over 687 million compounds for binding at the recently solved crystal structure of the main protease of SARS-CoV-2. After evaluation of off-target binding, we report a list of 11 drug-like compounds with improved binding free energy to the target protease in contrast to the cocrystallized peptidomimetic lead compound that suffers from poor pharmacokinetic properties. Furthermore, we identified one potent binder with comparable properties from the natural compound library.

1. Naringenin was very effective in inhibiting human coronaviruses infection

2. TPC2, the molecular target of Naringenin, was critical in regulating HCoV229E infection mechanism

3. Naringenin showed a strong antiviral activity against SARS-CoV-2

Among many compounds, naringenin (NAR) a flavonoid present in citrus fruits has been investigated for antiviral and anti-inflammatory properties like reducing viral replication and cytokine production. In this perspective, we summarize NAR potential anti-inflammatory role in COVID-19 associated risk factors and SARS-CoV-2 infection.

This review highlights the antiviral potential of naringenin in COVID-19 associated risk factors and its predicted therapeutic targets against SARS-CoV-2 infection.

The goal of the present review is to illustrate the rationale that links TPC channels to the mechanism of coronavirus infection, and how their inhibition by Nar could be an efficient pharmacological strategy to fight the current pandemic plague COVID-19.

In this review, the promising effects and possible mechanisms of action of naringenin, a citrus-derived flavonoid, against COVID-19 were discussed.