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1.
J Evid Based Integr Med ; 26: 2515690X211026193, 2021.
Article in English | MEDLINE | ID: covidwho-1298011

ABSTRACT

OBJECTIVES AND SETTING.: As the lethal COVID-19 pandemic enters its second year, the need for effective modalities of alleviation remains urgent. This includes modalities that can readily be used by the public to reduce disease spread and severity. Such preventive measures and early-stage treatments may temper the immediacy of demand for advanced anti-COVID measures (drugs, antibodies, vaccines) and help relieve strain also on other health system resources. DESIGN AND PARTICIPANTS.: We present results of a clinical study with a multi-component OTC "core formulation" regimen used in a multiply exposed adult population. Analysis of clinical outcome data from our sample of over 100 subjects - comprised of roughly equal sized regimen-compliant (test) and non-compliant (control) groups meeting equivalent inclusion criteria - demonstrates a strong statistical significance in favor of use of the core formulations. RESULTS.: While both groups were moderate in size, the difference between them in outcomes over the 20-week study period was large and stark: Just under 4% of the compliant test group presented flu-like symptoms, but none of the test group was COVID-positive; whereas 20% of the non-compliant control group presented flu-like symptoms, three-quarters of whom (15% overall of the control group) were COVID-positive. CONCLUSIONS.: Offering a low cost, readily implemented anti-viral approach, the study regimen may serve, at the least, as a stopgap modality and, perhaps, as a useful tool in combatting the pandemic.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Communicable Disease Control , Dietary Supplements , Pandemics , Adult , COVID-19/virology , Cinchona , Female , Humans , Ionophores/therapeutic use , Lysine/therapeutic use , Male , Middle Aged , Nonprescription Drugs , Quercetin/therapeutic use , SARS-CoV-2 , Severity of Illness Index , Treatment Outcome , Vitamins/therapeutic use , Zinc/therapeutic use
2.
Eur J Pharmacol ; 882: 173288, 2020 Sep 05.
Article in English | MEDLINE | ID: covidwho-959742

ABSTRACT

In December 2019, many pneumonia cases with unidentified sources appeared in Wuhan, Hubei, China, with clinical symptoms like viral pneumonia. Deep sequencing analysis of samples from lower respiratory tract revealed a novel coronavirus, called 2019 novel coronavirus (2019-nCoV). Currently there is a rapid global spread. World Health Organization declare the disease a pandemic condition. The pathologic source of this disease was a new RNA virus from Coronaviridae family, which was named COVID-19. SARS-CoV-2 entry starts with the binding of the spike glycoprotein expressed on the viral envelope to ACE2 on the alveolar surface followed by clathrin-dependent endocytosis of the SARS-CoV-2 and ACE2 complex. SARS-CoV-2 enters the cells through endocytosis process, which is possibly facilitated, via a pH dependent endosomal cysteine protease cathepsins. Once inside the cells, SARS-CoV-2 exploits the endogenous transcriptional machinery of alveolar cells to replicate and spread through the entire lung. Endosomal acidic pH for SARS-CoV-2 processing and internalization is critical. After entering the cells, it possibly activates or hijack many intracellular pathways in favor of its replication. In the current opinion article, we will explain the possible involvement of unfolded protein response as a cellular stress response to the SARS-CoV-2 infection.


Subject(s)
Alveolar Epithelial Cells/drug effects , Coronavirus Infections/drug therapy , Endoplasmic Reticulum/drug effects , Ionophores/pharmacology , Pneumonia, Viral/drug therapy , Alveolar Epithelial Cells/cytology , Alveolar Epithelial Cells/metabolism , Alveolar Epithelial Cells/virology , Angiotensin-Converting Enzyme 2 , Betacoronavirus/metabolism , COVID-19 , Clathrin-Coated Vesicles/drug effects , Clathrin-Coated Vesicles/metabolism , Coronavirus Infections/virology , Endocytosis/drug effects , Endoplasmic Reticulum/metabolism , Endosomes/drug effects , Endosomes/metabolism , Humans , Ionophores/therapeutic use , Pandemics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/virology , SARS-CoV-2 , Unfolded Protein Response/drug effects
3.
Biochim Biophys Acta Gen Subj ; 1865(2): 129801, 2021 02.
Article in English | MEDLINE | ID: covidwho-938766

ABSTRACT

BACKGROUND: Due to lack of approved drugs and vaccines, the medical world has resorted to older drugs, produced for viral infections and other diseases, as a remedy to combat COVID-19. The accumulating evidence from in vitro and in vivo studies for SARS-CoV and MERS-CoV have demonstrated that several polyphenols found in plants and zinc- polyphenol clusters have been in use as herbal medicines have antiviral activities against viruses with various mechanisms. SCOPE OF REVIEW: Curcumin, zinc and zinc-ionophores have been considered as nutraceuticals and nutrients showing great antiviral activities with their medicinal like activities. MAJOR CONCLUSIONS: In this work, we discussed the potential prophylactic and/or therapeutic effects of curcumin, zinc and zinc-ionophores in treatment of viral infections including COVID-19. GENERAL SIGNIFICANCE: Curcuminoids and Zinc classified as nutraceuticals under GRAS (Generally Recognized As Safe) by FDA can provide complementary treatment for COVID 19 patients with their immunity-boosting and antiviral properties.


Subject(s)
COVID-19/therapy , Dietary Supplements , Plant Extracts/therapeutic use , Plant Preparations/therapeutic use , Polyphenols/therapeutic use , Zinc/chemistry , Antiviral Agents/therapeutic use , Curcumin/therapeutic use , Cytokine Release Syndrome , Food , Humans , Inflammation , Ionophores/therapeutic use , Pandemics , Trace Elements/therapeutic use , Virus Replication
4.
Med Hypotheses ; 145: 110333, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-813777

ABSTRACT

Zinc and the combination with zinc ionophore have been reported in basic research and several clinical investigations as a potentially viable and economical preventive and therapeutic options for COVID-19 treatment. Zinc is a vital microelement that actively supports respiratory epithelium barrier integrity, innate and adaptive immune functions, and inflammatory regulations. Moreover, zinc may also prevent viral entry, suppress viral replication, and mitigate the damages due to oxidative stress and hyperinflammatory reaction in patients with respiratory infections. Hinokitiol (ß-thujaplicin) is a natural monoterpenoid and is considered as a safe zinc ionophore to help zinc transport into cells. It has been widely used in skin and oral care, and therapeutic products for its potent antiviral, antimicrobial, antifungal, anti-inflammatory, and anticancer applications. The ongoing COVID-19 pandemic and the significant morbidity and mortality exist in the high-risk group of patients associated with other respiratory infections such as influenza, respiratory syncytial virus, and dengue fever. There is an urgent need for the development of inexpensive, safe, and effective therapeutics to prevent and treat these viral infections. Considering that hydroxychloroquine (HCQ), the most studied zinc ionophore drug for COVID-19, is linked to potentially serious side effects, we propose the implementation of hinokitiol as a zinc ionophore and anti-infective agent for the prevention and treatment of COVID-19 and other viral infections.


Subject(s)
Anti-Infective Agents/therapeutic use , COVID-19/prevention & control , Ionophores/therapeutic use , Monoterpenes/therapeutic use , Tropolone/analogs & derivatives , Zinc/chemistry , Antiviral Agents/therapeutic use , Homeostasis , Humans , Hydroxychloroquine/pharmacology , Models, Theoretical , Risk , Tropolone/therapeutic use
5.
J Med Microbiol ; 69(10): 1228-1234, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-767039

ABSTRACT

Introduction. COVID-19 has rapidly emerged as a pandemic infection that has caused significant mortality and economic losses. Potential therapies and prophylaxis against COVID-19 are urgently needed to combat this novel infection. As a result of in vitro evidence suggesting zinc sulphate may be efficacious against COVID-19, our hospitals began using zinc sulphate as add-on therapy to hydroxychloroquine and azithromycin.Aim. To compare outcomes among hospitalized COVID-19 patients ordered to receive hydroxychloroquine and azithromycin plus zinc sulphate versus hydroxychloroquine and azithromycin alone.Methodology. This was a retrospective observational study. Data was collected from medical records for all patients with admission dates ranging from 2 March 2020 through to 11 April 2020. Initial clinical characteristics on presentation, medications given during the hospitalization, and hospital outcomes were recorded. The study included patients admitted to any of four acute care NYU Langone Health Hospitals in New York City. Patients included were admitted to the hospital with at least one positive COVID-19 test and had completed their hospitalization. Patients were excluded from the study if they were never admitted to the hospital or if there was an order for other investigational therapies for COVID-19.Results. Patients taking zinc sulphate in addition to hydroxychloroquine and azithromycin (n=411) and patients taking hydroxychloroquine and azithromycin alone (n=521) did not differ in age, race, sex, tobacco use or relevant comorbidities. The addition of zinc sulphate did not impact the length of hospitalization, duration of ventilation or intensive care unit (ICU) duration. In univariate analyses, zinc sulphate increased the frequency of patients being discharged home, and decreased the need for ventilation, admission to the ICU and mortality or transfer to hospice for patients who were never admitted to the ICU. After adjusting for the time at which zinc sulphate was added to our protocol, an increased frequency of being discharged home (OR 1.53, 95 % CI 1.12-2.09) and reduction in mortality or transfer to hospice among patients who did not require ICU level of care remained significant (OR 0.449, 95 % CI 0.271-0.744).Conclusion. This study provides the first in vivo evidence that zinc sulphate may play a role in therapeutic management for COVID-19.


Subject(s)
Azithromycin/therapeutic use , Coronavirus Infections/drug therapy , Hydroxychloroquine/therapeutic use , Pneumonia, Viral/drug therapy , Zinc Sulfate/therapeutic use , Betacoronavirus/drug effects , COVID-19 , Cell Membrane Permeability/drug effects , Drug Therapy, Combination , Hospitalization , Humans , Ionophores/therapeutic use , Length of Stay , Pandemics , Retrospective Studies , SARS-CoV-2
6.
J Inorg Biochem ; 227: 111661, 2022 02.
Article in English | MEDLINE | ID: covidwho-1516298

ABSTRACT

Ionophores are a diverse class of synthetic and naturally occurring ion transporter compounds which demonstrate both direct and in-direct antimicrobial properties against a broad panel of bacterial, fungal, viral and parasitic pathogens. In addition, ionophores can regulate the host-immune response during communicable and non-communicable disease states. Although the clinical use of ionophores such as Amphotericin B, Bedaquiline and Ivermectin highlight the utility of ionophores in modern medicine, for many other ionophore compounds issues surrounding toxicity, bioavailability or lack of in vivo efficacy studies have hindered clinical development. The antimicrobial and immunomodulating properties of a range of compounds with characteristics of ionophores remain largely unexplored. As such, ionophores remain a latent therapeutic avenue to address both the global burden of antimicrobial resistance, and the unmet clinical need for new antimicrobial therapies. This review will provide an overview of the broad-spectrum antimicrobial and immunomodulatory properties of ionophores, and their potential uses in clinical medicine for combatting infection.


Subject(s)
Anti-Infective Agents , Drug Resistance/drug effects , Infections/drug therapy , Ionophores , Anti-Infective Agents/chemistry , Anti-Infective Agents/therapeutic use , Humans , Infections/microbiology , Ionophores/chemistry , Ionophores/therapeutic use
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