scholarly journals Virucidal activity of Nasaleze Cold® & Flu Blocker and Nasaleze® Travel in cell cultures infected with human pathogenic coronavirus 229-E

2021 ◽  
Author(s):  
Nigel Hunt ◽  
Louise Suleman ◽  
Peter D Josling ◽  
Todor Popov
Keyword(s):  
In Vitro Study ◽  
Test Substance ◽  
Virucidal Activity ◽  
Viral Titre ◽  
Human Coronavirus ◽  
Test Formulation ◽  
Optimal Dosing ◽  
Powder Cellulose ◽  
Human Coronavirus 229E

This in vitro study determined the anti-viral efficacy of a unique blend of powder cellulose supplemented with powdered garlic extract (PGE) and a signalling agent. The composition, presented as Nasaleze Cold & Flu Blocker/Nasaleze Travel, was assessed against Human Coronavirus 229E, CoV 229E {ATCC VR-740} in an in vitro experiment. The test substance was used at sub-optimal dosing levels to explore its prevention and treatment capabilities. The virucidal activity of this novel formulation was measured at 48, 72 and 112 hour periods after incubation. Results showed strong reductions in viral titre of Coronavirus 229E compared to a control, while no toxicity to human cells from the test formulation was noted. The extract Nasaleze Cold/Travel showed potential to be used as a therapeutic and preventive agent. The data reconfirms the established anti-viral activity of this formulation acting as a barrier preventing the virus from accessing the nasal mucosa and disrupting its replication.

scholarly journals Flavonols and dihydroflavonols inhibit the main protease activity of SARS-CoV-2 and the replication of human coronavirus 229E

2021 ◽  
Author(s):  
Yue Zhu ◽  
Frank Scholle ◽  
Samantha C. Kisthardt ◽  
Deyu Xie
Keyword(s):  
Docking Simulation ◽  
Binding Pocket ◽  
Developed Countries ◽  
Host Cells ◽  
Human Coronavirus ◽  
Main Protease ◽  
Ic50 Values ◽  
In Vitro Inhibition ◽  
Human Coronavirus 229E

Since December 2019, the deadly novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the current COVID-19 pandemic. To date, vaccines are available in the developed countries to prevent the infection of this virus, however, medicines are necessary to help control COVID-19. Human coronavirus 229E (HCoV-229E) causes the common cold. The main protease (Mpro) is an essential enzyme required for the multiplication of these two viruses in the host cells, and thus is an appropriate candidate to screen potential medicinal compounds. Flavonols and dihydroflavonols are two groups of plant flavonoids. In this study, we report docking simulation with two Mpro enzymes and five flavonols and three dihydroflavonols, in vitro inhibition of the SARS-CoV-2 Mpro, and in vitro inhibition of the HCoV 229E replication. The docking simulation results predicted that (+)-dihydrokaempferol, (+)-dihydroquercetin, (+)-dihydromyricetin, kaempferol, quercetin, myricentin, isoquercetin, and rutin could bind to at least two subsites (S1, S1', S2, and S4) in the binding pocket and inhibit the activity of SARS-CoV-2 Mpro. Their affinity scores ranged from -8.8 to -7.4. Likewise, these compounds were predicted to bind and inhibit the HCoV-229E Mpro activity with affinity scores ranging from -7.1 to -7.8. In vitro inhibition assays showed that seven available compounds effectively inhibited the SARS-CoV-2 Mpro activity and their IC50 values ranged from 0.125 to 12.9 uM. Five compounds inhibited the replication of HCoV-229E in Huh-7 cells. These findings indicate that these antioxidative flavonols and dihydroflavonols are promising candidates for curbing the two viruses.

scholarly journals In-vitro virucidal activity of hypothiocyanite and hypothiocyanite/lactoferrin mix against SARS-CoV-2

2020 ◽  
Author(s):  
Luca Cegolon ◽  
Mattia Mirandola ◽  
Claudio Salaris ◽  
Maria Vittoria Salvati ◽  
Cristiano Salata ◽  
...  
Keyword(s):  
Upper Airway ◽  
In Vitro Study ◽  
Alveolar Type ◽  
Virucidal Activity ◽  
Human Immune System ◽  
Pharmacological Interventions ◽  
Protection Measures ◽  
Viral Spread

ABSTRACTSARS-CoV-2 replicates efficiently in the upper airway during prodromal stage with resulting viral shedding into the environment from patients with active disease as well as from asymptomatic individuals. So far, virus spread has been exclusively contained by non-pharmacological interventions (social distancing, face masks, hand washing and several measures limiting business activities or movement of individuals)1,2. There is a need to find pharmacological interventions to mitigate the viral spread, supporting yet limiting the existing health protection measures while an effective and safe vaccine will hopefully become available. Hypothiocyanite and lactoferrin as part of the innate human immune system were shown to have a large spectrum of cidal activity against bacteria, fungi and viruses2,3. To test their virucidal activity against SARS-CoV-2 we conducted an in-vitro study. Here we show a dose-dependent virucidal activity of hypothiocyanite at micromolar concentrations, slightly improved by the presence of lactoferrin. The two substances are devoid of any cytotoxicity and may be administered combined by aerosol to exploit their antiviral activity at the port of entry (mouth, nasal cavity, conjunctiva) or exit (mouth, through emission of respiratory droplets) of SARS-CoV-2 in the human body. Furthermore, aerosol with hypothiocyanite and lactoferrin combined could also have a therapeutic effect in the lower respiratory tract, at the level of gas exchange units of the lung, preventing the devastating infection of alveolar type II cells where ACE2 is highly expressed. An in-vivo validation of in-vitro results is urgently required.

scholarly journals Virucidal Activity of the Antiseptic Mouthwash and Dental Gel Containing Anionic Phthalocyanine Derivative: In vitro Study

2021 ◽  
Vol Volume 13 ◽  
pp. 269-274
Author(s):  
Caique Santos ◽  
Bernardo da Fonseca Orcina ◽  
Verônica Caroline Brito Reia ◽  
Lucas Gabriel Ribeiro ◽  
Rejane MT Grotto ◽  
...  
Keyword(s):  
In Vitro Study ◽  
Vitro Study ◽  
Virucidal Activity ◽  
Phthalocyanine Derivative

scholarly journals Assessment of a novel mucolytic solution for dissolving mucus in pseudomyxoma peritonei: an ex vivo and in vitro study

2017 ◽  
Vol 2 (2) ◽  
pp. 111-117 ◽  
Author(s):  
Krishna Pillai ◽  
Javed Akhter ◽  
David L. Morris
Keyword(s):  
Pseudomyxoma Peritonei ◽  
Hyperthermic Intraperitoneal Chemotherapy ◽  
Ex Vivo ◽  
In Vitro Study ◽  
Ht29 Cell ◽  
Test Solution ◽  
Test Formulation ◽  
Peritoneal Washing ◽  
Ht29 Cell Line

AbstractBackgroundPseudomyxoma peritonei (PMP) is difficult to treat. Intraperitoneal delivery of mucolytic solutions might potentially improve therapy, in addition to surgical cytoreduction and hyperthermic intraperitoneal chemotherapy.MethodsComparison of mucolytic effect of two formulations (control: bromelain 300 µg/mL+N-Acetylcystein 250 mM; test: bromelain 200 µg/mL+200 mM cysteamine) in vitro on a mucin producing cell lines (HT29) and ex vivo on mucus obtained from 18 PMP patients. Mucin plugs were classified according to their density into three categories: hard, semi hard and soft. Simulation of peritoneal washing ex vivo using a closed heated circulating pump.ResultsSolubilisation was faster with the test vs. the control formulation (90 vs. 180 min) for dissolving the soft mucin plugs (p < 0.05). The test solution was also more effective in dissolving the hard mucus plugs compared to control (82.5±2.74 % vs. 36.33±3.27 %). All mucin types disintegrated in simulated peritoneal washing. Cytotoxicity of the test solution on HT29 cell line was time-dependent.ConclusionsThe test formulation is more effective and faster than the control formulation in dissolving mucus plugs of various densities. Mucus plugs were all solubilised after 40 min in simulated peritoneal washing. This novel mucolytic formulation might pave the way for an effective and less invasive therapy of PMP in the future.

Proteolytic Processing at the Amino Terminus of Human Coronavirus 229E Gene 1-Encoded Polyproteins: Identification of a Papain-Like Proteinase and Its Substrate

1998 ◽  
Vol 72 (2) ◽  
pp. 910-918 ◽  
Author(s):  
Jens Herold ◽  
Alexander E. Gorbalenya ◽  
Volker Thiel ◽  
Barbara Schelle ◽  
Stuart G. Siddell
Keyword(s):  
Amino Acids ◽  
Cleavage Site ◽  
Cysteine Proteinase ◽  
Proteolytic Processing ◽  
Amino Terminus ◽  
Human Coronavirus ◽  
Amino Terminal ◽  
Cleavage Assay ◽  
Human Coronavirus 229E

ABSTRACT Expression of the coronavirus gene 1-encoded polyproteins, pp1a and pp1ab, is linked to a series of proteolytic events involving virus-encoded proteinases. In this study, we used transfection and immunoprecipitation assays to show that the human coronavirus 229E-encoded papain-like cysteine proteinase, PCP1, is responsible for the release of an amino-terminal protein, p9, from the gene 1-encoded polyproteins. The same protein, p9, has also been identified in virus-infected cells. Furthermore, using an in vitrotrans-cleavage assay, we defined the proteolytic cleavage site at the carboxyl terminus of p9 as pp1a-pp1ab amino acids Gly-111 and Asn-112. These results and a comparative sequence analysis suggest that substrate positions P1 and P5 seem to be the major determinants of the PCP1 cleavage site and that the latter can occupy a variable position at the amino terminus of the coronavirus pp1a and pp1ab polyproteins. By combining the trans-cleavage assay with deletion mutagenesis, we were also able to locate the boundaries of the active PCP1 domain between pp1a-pp1ab amino acids Gly-861–Glu-975 and Asn-1209–Gln-1285. Finally, codon mutagenesis was used to show that Cys-1054 and His-1205 are essential for PCP1 proteolytic activity, suggesting that these amino acids most likely have a catalytic function.

scholarly journals Exposure–response modelling approaches for determining optimal dosing rules in children

2020 ◽  
Vol 29 (9) ◽  
pp. 2583-2602
Author(s):  
Ian Wadsworth ◽  
Lisa V Hampson ◽  
Björn Bornkamp ◽  
Thomas Jaki
Keyword(s):  
Recursive Partitioning ◽  
Age Groups ◽  
In Vitro Study ◽  
Model Parameters ◽  
Response Model ◽  
B Splines ◽  
Model Based ◽  
Exposure Response ◽  
Optimal Dosing

Within paediatric populations, there may be distinct age groups characterised by different exposure–response relationships. Several regulatory guidance documents have suggested general age groupings. However, it is not clear whether these categorisations will be suitable for all new medicines and in all disease areas. We consider two model-based approaches to quantify how exposure–response model parameters vary over a continuum of ages: Bayesian penalised B-splines and model-based recursive partitioning. We propose an approach for deriving an optimal dosing rule given an estimate of how exposure–response model parameters vary with age. Methods are initially developed for a linear exposure–response model. We perform a simulation study to systematically evaluate how well the various approaches estimate linear exposure–response model parameters and the accuracy of recommended dosing rules. Simulation scenarios are motivated by an application to epilepsy drug development. Results suggest that both bootstrapped model-based recursive partitioning and Bayesian penalised B-splines can estimate underlying changes in linear exposure–response model parameters as well as (and in many scenarios, better than) a comparator linear model adjusting for a categorical age covariate with levels following International Conference on Harmonisation E11 groupings. Furthermore, the Bayesian penalised B-splines approach consistently estimates the intercept and slope more accurately than the bootstrapped model-based recursive partitioning. Finally, approaches are extended to estimate Emax exposure–response models and are illustrated with an example motivated by an in vitro study of cyclosporine.

scholarly journals Cytokine Responses in Severe Acute Respiratory Syndrome Coronavirus-Infected Macrophages In Vitro: Possible Relevance to Pathogenesis

2005 ◽  
Vol 79 (12) ◽  
pp. 7819-7826 ◽  
Author(s):  
Chung Y. Cheung ◽  
Leo L. M. Poon ◽  
Iris H. Y. Ng ◽  
Winsie Luk ◽  
Sin-Fun Sia ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Influenza A ◽  
Infectious Virus ◽  
Expression Profiles ◽  
Enzyme Linked Immunosorbent Assay ◽  
Viral Gene ◽  
Human Coronavirus ◽  
Influenza A H1n1 ◽  
Human Coronavirus 229E

ABSTRACT The pathogenesis of severe acute respiratory syndrome (SARS) remains unclear. Macrophages are key sentinel cells in the respiratory system, and it is therefore relevant to compare the responses of human macrophages to infections with the SARS coronavirus (SARS-CoV) and other respiratory viruses. Primary human monocyte-derived macrophages were infected with SARS-CoV in vitro. Virus replication was monitored by measuring the levels of positive- and negative-strand RNA, by immunofluorescence detection of the SARS-CoV nucleoprotein, and by titration of the infectious virus. The gene expression profiles of macrophages infected with SARS-CoV, human coronavirus 229E, and influenza A (H1N1) virus were compared by using microarrays and real-time quantitative reverse transcriptase PCR. Secreted cytokines were measured with an enzyme-linked immunosorbent assay. SARS-CoV initiated viral gene transcription and protein synthesis in macrophages, but replication was abortive and no infectious virus was produced. In contrast to the case with human coronavirus 229E and influenza A virus, there was little or no induction of beta interferon (IFN-β) in SARS-CoV-infected macrophages. Furthermore, SARS-CoV induced the expression of chemokines such as CXCL10/IFN-γ-inducible protein 10 and CCL2/monocyte chemotactic protein 1. The poor induction of IFN-β, a key component of innate immunity, and the ability of the virus to induce chemokines could explain aspects of the pathogenesis of SARS.

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