Coronavirus

A. Goc, W. Sumera, M. Rath, A. Niedzwiecki

European Journal of Microbiology and Immunology, June 2023

Abstract

SARS-CoV-2 infection still poses health threats especially to older and immunocompromised individuals. New emerging variants of SARS-CoV-2, including Omicron and Arcturus, have been challenging the effectiveness of humoral immunity resulting from repeated vaccination and infection. With recent study implying a wave of new mutants in vaccinated people making them more susceptible to the newest variants and fueling a rapid viral evolution, there is a need for alternative or adjunct approaches against coronavirus infections other than vaccines. Our earlier work indicated that a specific combination of micronutrients and phytochemicals can inhibit key infection mechanisms shared by SARS-CoV-2 and its variants in vitro. Here we demonstrate in vivo that an intake of this micronutrient combination before and during infection of mice with engineered SARS-CoV-2 virions and HCoV-229E virus results in a significant decrease in viral load and level of spike protein in the lungs. This was accompanied by decreased inflammatory response, including TNFα, IL1β, ILα, and IL17. These and our earlier results confirm that by targeting multiple mechanisms simultaneously by a combination treatment we can effectively and safely challenge SARS-CoV-2 and HCoV-229E virus. If clinically confirmed, such an approach could complement already in-use preventive and therapeutic strategies against coronavirus infections.

Read more: Phytochemicals and micronutrients in suppressing infectivity caused by SARS-CoV-2 virions and seasonal coronavirus HCoV-229E in vivo

Goc A, Sumera W, Rath M, Niedzwiecki A.

Scientific Reports 2022, 12:19114

Abstract

Fatty acids belong to a group of compounds already acknowledged for their broad antiviral efficacy. However, little is yet known about their effect on replication of human coronaviruses. To shed light on this subject, we first screened 15 fatty acids, three lipid-soluble vitamins, and cholesterol, on SARSCoV-2 RdRp, and identified the four fatty acids with the highest RdRp inhibitory potential. Among them, linoleic acid was found to have the greatest interaction with SARS-CoV-2 RdRp, with its direct binding to the cavity formed by the RNA double helix and protein. Linoleic acid forms hydrophobic interactions with multiple residues, and at the same time forms electrostatic interactions including the hydrogen bond with Lys593 and Asp865. In line with these results, a dose-dependent inhibition of HCoV-OC43 replication in vitro was observed, additionally strengthened by data from in vivo study, which also confirmed anti-inflammatory potential of linoleic acid. Based on these results, we concluded that our study provides a new understanding of the antiviral properties of fatty acids against human coronaviruses including the SARS-CoV-2 strain. Particularly, they lays down a new prospect for linoleic acid’s RdRp-inhibitory activity, as a candidate for further studies, which are warranted to corroborate the results presented here.…

Read more: Linoleic acid binds to SARS‑CoV‑2 RdRp and represses replication of seasonal human coronavirus OC43

Goc A, Niedzwiecki A, Rath M.

European Journal of Microbiology and Immunology, June 2022

Abstract

Naturally-occurring compounds are acknowledged for their broad antiviral efficacy. Little is however known about their mutual cooperation. Here, we evaluated in vitro efficacy of the defined mixture of agents against the RdRp complex of the original SARS-CoV-2 and Omicron variant. This composition of vitamin C, N-acetylcysteine, resveratrol, theaflavin, curcumin, quercetin, naringenin, baicalin, and broccoli extract showed to inhibit activity of RdRp/nsp7/nsp8 both these variants. In vitro exposure of recombinant RdRp complex to individual compounds of this composition pointed to quercetin as the driving inhibitory compound. The outcome of this study supports the motion of antiviral efficacy of natural compounds against SARS-CoV-2 and Omicron and implies that their reciprocal or mutual interaction may augment antiviral action through simultaneous effect on different mechanisms. Consequently, this makes it more difficult for an infectious agent to evade all these mechanisms at the same time. Considering the urgency in finding effective prevention, but also side-effects free treatment of COVID-19 our results call for clinical affirmation of the benefits of this micronutrient combination in both preventive and therapeutic aspects. Whether observed effects can be achieved, by concentrations of the active agents used in these in vitro experiments, in in vivo or clinical setting warrants further study.…

Read more: Composition of naturally occurring compounds decreases activity of Omicron and SARS-CoV-2 RdRp complex

Goc A, Niedzwiecki A, Ivanov V, Ivanova S, Rath M.

European Journal of Microbiology and Immunology, Jan 2022

Abstract

Despite vaccine availability, the global spread of COVID-19 continues, largely facilitated by emerging SARS-CoV-2 mutations. Our earlier research documented that a specific combination of plant-derived compounds can inhibit SARS-CoV-2 binding to its ACE2 receptor and controlling key cellular mechanisms of viral infectivity. In this study, we evaluated the efficacy of a defined mixture of plant extracts and micronutrients against original SARS-CoV-2 and its Alpha, Beta, Gamma, Delta, Kappa,and Mu variants. The composition containing vitamin C, N-acetylcysteine, resveratrol, theaflavin, curcumin, quercetin, naringenin, baicalin, and broccoli extract demonstrated a highest efficacy by inhibiting the receptor-binding domain (RBD) binding of SARS-CoV-2 to its cellular ACE2 receptor by 90%. In vitro exposure of test pseudo-typed variants to this formula for 1 h before or simultaneously administrated to human pulmonary cells resulted in up to 60% inhibition in their cellular entry. Additionally, this composition significantly inhibited other cellular mechanisms of viral infectivity, including the activity of viral RdRp, furin, and cathepsin L. These findings demonstrate the efficacy of natural compounds against SARS-CoV-2 including its mutated forms through pleiotropic mechanisms. Our results imply that simultaneous inhibition of multiple mechanisms of viral infection of host cells could be an effective strategy to prevent SARS-CoV-2 infection.…

Read more: Inhibitory effects of specific combination of natural compounds against SARS-CoV-2 and its Alpha, Beta, Gamma, Delta, Kappa, and Mu variants

Goc A, Ivanov V, Ivanova S, Chatterjee M, Rath M, Niedzwiecki A

European Journal of Biology and Biotechnology, Vol 2(5), 2021

DOI: http://dx.doi.org/10.24018/ejbio.2021.2.5.258

Abstract

SARS-CoV-2 pandemic remains a challenge to human health and economy worldwide. Previously we have shown that a combination of active plant-derived compounds and plant extracts can dose-dependently inhibit binding of RBD-spike protein SARS-CoV-2 to the ACE2receptor and its expression on human alveolar epithelial cells. Here we use eGFP-luciferase-SARS-CoV-2 spike protein pseudo-virions and SARS-CoV-2-RdRp, to show if the antiviral effectiveness of this combination of plant-derived compounds and plant extracts expands to other important key mechanisms of SARS-CoV-2 infection. Or results revealed that this combination of five plant-derived compounds inhibited the attachment of the SARS-CoV-2 pseudo-typed particles with lung hACE2/A549 cells.…

Read more: Simultaneous Inhibition of SARS-CoV-2 Infectivity by a Specific Combination of Plant-derived Compounds

Goc A, Sumera W, Rath M, Niedzwiecki A

PLOS ONE 16(6): e0253489. 2021

Abstract

In the pursuit of suitable and effective solutions to SARS-CoV-2 infection, we investigated the efficacy of several phenolic compounds in controlling key cellular mechanisms involved in its infectivity. The way the SARS-CoV-2 virus infects the cell is a complex process and comprises four main stages: attachment to the cognate receptor, cellular entry, replication and cellular egress. Since, this is a multi-part process, it creates many opportunities to develop effective interventions.…

Read more: Phenolic compounds disrupt spike-mediated receptor-binding and entry of SARS-CoV-2 pseudo-virions

Goc A, Niedzwiecki A, Rath M

Scientific Reports 2021; 11:5207

The strain SARS-CoV-2, newly emerged in late 2019, has been identifed as the cause of COVID19 and the pandemic declared by WHO in early 2020. Although lipids have been shown to possess antiviral efcacy, little is currently known about lipid compounds with anti-SARS-CoV-2 binding and entry properties. To address this issue, we screened, overall, 17 polyunsaturated fatty acids, monounsaturated fatty acids and saturated fatty acids, as wells as lipid-soluble vitamins. In performing target-based ligand screening utilizing the RBD-SARS-CoV-2 sequence, we observed that polyunsaturated fatty acids most efectively interfere with binding to hACE2, the receptor for SARSCoV-2. Using a spike protein pseudo-virus, we also found that linolenic acid and eicosapentaenoic acid signifcantly block the entry of SARS-CoV-2. In addition, eicosapentaenoic acid showed higher efcacy than linolenic acid in reducing activity of TMPRSS2 and cathepsin L proteases, but neither of the fatty acids afected their expression at the protein level. Also, neither reduction of hACE2 activity nor binding to the hACE2 receptor upon treatment with these two fatty acids was observed. Although further in vivo experiments are warranted to validate the current fndings, our study provides a new insight into the role of lipids as antiviral compounds against the SARS-CoV-2 strain.…

Read more: Polyunsaturated ω‑3 fatty acids inhibit ACE2‑controlled SARS‑CoV‑2 binding and cellular entry

Ivanov V, Goc A, Ivanova S, Niedzwiecki A, Rath M

Infectious Diseases: Research and Treatment. January 2021. Volume 14: 1–7

Abstract

Background: Angiotensin-converting enzyme II or ACE2 is an integral membrane protein present on many types of cells, including vascular endothelial cells and lung alveolar epithelial cells. This receptor serves as the entry point for SARS-coronaviruses (SARS-CoVs), including a novel coronavirus 2019-nCoV. Limited availability of these receptors can thwart cellular entry of this virus.…

Read more: Inhibition of ACE2 expression by Ascorbic acid alone and its combination with other natural compounds

Niedzwiecki A, Rath M

Journal of Cellular Medicine and Natural Health, Jan 19, 2021

Global impact of COVID-19 pandemic

Over 70 million cases of COVID-19 had been confirmed worldwide by mid-December 2020,
and the disease had claimed more than 1.6 million lives. According to a joint statement
issued on 13 October 2020 by ILO, FAO, IFAD and WHO “the COVID-19 pandemic has led to
a dramatic loss of human life worldwide and presents an unprecedented challenge to public
health, food systems and the world of work. The economic and social disruption caused by
the pandemic is devastating: tens of millions of people are at risk of falling into extreme
poverty, while the number of undernourished people, currently estimated at nearly 690
million, could increase to over 800 million by the end the year”. 1  In addition, the wide socio-
economic impact of this pandemic has threatened the sustainability of all sectors of society
all over the globe, impacting mental health, the food supply, medical services, education,
and energy, among many other aspects. 2
This statement highlights the important, but often overlooked, fact that healthy nutrition
supplying a full spectrum of micronutrients is the foundation of our immune system function
and provides effective protection against infections, including COVID-19.

Full Study:

Read more: Scientific basis of micronutrient applications as an effective, safe, and affordable global public health strategy to help control the coronavirus pandemic

Sumera W, Goc A, Niedzwiecki A, Rath M

Journal of Cellular Medicine and Natural Health, Aug 28, 2020

Abstract

Infectious diseases have become a growing health problem worldwide. Thus, the search for novel non-toxic and effective approaches with immune system- enhancing effects, so it can resist and fight these infections is still sought after. It has been firmly established that both nutrition and the availability of specific micronutrients are important for achieving optimum immunity.…

Read more: The micronutrient combination with immune-enhancing effects

Goc A, Sumera W, Ivanov V, Niedzwiecki A, Rath M

Journal of Cellular Medicine and Natural Health, Aug 14, 2020

Abstract

Introduction: The coronavirus pandemic poses an unprecedented challenge to human health as well as global economies. The quest for vaccines and other approaches to this pandemic thus far focuses on synthetic molecules that are – predictably – associated with a variable degree of adverse effects.…

Read more: Micronutrient combination inhibits two key steps of coronavirus (SARS-CoV-2) infection: viral binding to ACE2 receptor and its cellular expression

Ivanov V, Ivanova S, Niedzwiecki A, Rath M

Journal of Cellular Medicine and Natural Health, July 2, 2020

SUMMARY

Optimum micronutrient intake is the only scientifically proven way to improve general immune resistance against infections, a fact documented in every leading textbook of biology.  This study provides scientific evidence that, in addition, specific micronutrient compositions are powerful tools in the fight against the COVID-19 pandemic.

Both, SARS-CoV-2 – the virus that causes the current pandemic – and other coronaviruses enter body cells via a specific receptor, the Angiotensin-Converting-Enzyme 2 (ACE2). The ACE2 receptor is expressed by many cell types, including lung epithelial cells as well as endothelial cells of the vascular system.…

Read more: Effective and safe global public health strategy to fight the COVID-19 pandemic: Specific micronutrient composition inhibits Coronavirus cell-entry receptor (ACE2) expression