Hypothiocyanite and Hypothiocyanite/Lactoferrin Mixture Exhibit Virucidal Activity In Vitro against SARS-CoV-2

SARS-CoV-2 replicates efficiently in the upper airways during the prodromal stage, resulting in environmental viral shedding from patients with active COVID-19 as well as from asymptomatic individuals. There is a need to find pharmacological interventions to mitigate the spread of COVID-19. Hypothiocyanite and lactoferrin are molecules of the innate immune system with a large spectrum cidal activity. The Food and Drug Administration and the European Medicines Agency designated the hypothiocyanite and lactoferrin combination as an orphan drug. We report an in vitro study showing that micromolar concentrations of hypothiocyanite exhibit dose- and time-dependent virucidal activity against SARS-CoV-2 and that the latter is slightly enhanced by the simultaneous presence of lactoferrin.

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In-vitro Virucidal Activity of Hypothiocyanite and Hypothiocyanite/lactoferrin Mix Against SARS-CoV-2

10.21203/rs.3.rs-131956/v1 ◽

2020 ◽

Author(s):

Luca Cegolon ◽

Mattia Mirandola ◽

Claudio Salaris ◽

Maria Salvati ◽

Cristiano Salata ◽

...

Keyword(s):

Innate Immune ◽

European Medicines Agency ◽

Virucidal Activity ◽

Pharmacological Interventions ◽

Prodromal Stage ◽

Upper Airways ◽

Viral Shedding ◽

Asymptomatic Individuals ◽

Dose Dependent

Abstract SARS-CoV-2 replicates efficiently in the upper airways during the prodromal stage, with resulting viral shedding into the environment from patients with active COVID-19 as well as from asymptomatic individuals. There is a need to find pharmacological interventions to mitigate the spread of COVID-19. Hypothiocyanite and lactoferrin are molecules of the innate immune system with a large spectrum cidal activity and easy to administer by aerosol inhalation. The combination of the above two molecules was designated as orphan drug by the Food and Drug Administration and the European Medicines Agency. Here we found a dose-dependent as well as time-dependent virucidal activity of hypothiocyanite at micromolar concentrations, slightly improved by lactoferrin, against SARS-CoV-2. The two substances individually tested were devoid of any cytotoxicity.

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

10.1101/2020.11.17.387571 ◽

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.

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Methylene Blue has a potent antiviral activity against SARS-CoV-2 and H1N1 influenza virus in the absence of UV-activation in vitro

10.21203/rs.3.rs-134789/v1 ◽

2021 ◽

Author(s):

Valeria Cagno1 ◽

Chiara Medaglia ◽

Andreas Cerny ◽

Thomas Cerny ◽

Arnaud Zwygart ◽

...

Keyword(s):

Methylene Blue ◽

Influenza Virus ◽

Antiviral Activity ◽

Uv Light ◽

H1n1 Influenza ◽

European Medicines Agency ◽

Virus H1n1 ◽

Therapeutic Activity ◽

Virucidal Activity

Abstract Methylene blue is an FDA (food and drug administration) and EMA (european medicines agency) approved drug with an excellent safety profile. It displays broad-spectrum virucidal activity in the presence of UV light and has been shown to be effective in inactivating various viruses in blood products prior to transfusions. In addition, its use has been validated for methemoglobinemia and malaria treatment. In this study, we first evaluated the virucidal activity of methylene blue against Influenza Virus H1N1 upon different incubation times and in the presence or absence of light activation, and then against SARS-CoV-2. We further assessed the therapeutic activity of methylene blue by administering it to cells previously infected with SARS-CoV-2. Finally, we examined the effect of co-administration of the drug together with immune serum. Our findings reveal that methylene blue displays virucidal preventive or therapeutic activity against Influenza Virus H1N1 and SARS-CoV-2 at low micromolar concentrations and in the absence of UV activation. We also confirm that MB antiviral activity is based on several mechanisms of action as the degradation of genomic RNA is only observed in the presence of light and after long exposure. Our work supports the interest of testing methylene blue in clinical studies to confirm a preventive or therapeutic efficacy against both Influenza Virus H1N1 and SARS-CoV-2 infections.

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

Clinical Cosmetic and Investigational Dentistry ◽

10.2147/ccide.s315419 ◽

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

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A simple method for the in vitro study of the virucidal activity of disinfectants

Journal of Virological Methods ◽

10.1016/s0166-0934(99)00170-6 ◽

2000 ◽

Vol 86 (1) ◽

pp. 21-24 ◽

Cited By ~ 6

Author(s):

S Valot ◽

D Edert ◽

A Le Faou

Keyword(s):

In Vitro Study ◽

Vitro Study ◽

Virucidal Activity ◽

Simple Method

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Methylene Blue has a potent antiviral activity against SARS-CoV-2 and H1N1 influenza virus in the absence of UV-activation in vitro

Scientific Reports ◽

10.1038/s41598-021-92481-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Valeria Cagno ◽

Chiara Medaglia ◽

Andreas Cerny ◽

Thomas Cerny ◽

Arnaud Charles-Antoine Zwygart ◽

...

Keyword(s):

Methylene Blue ◽

Influenza Virus ◽

Antiviral Activity ◽

Uv Light ◽

Rna Degradation ◽

European Medicines Agency ◽

Virus H1n1 ◽

Therapeutic Activity ◽

Virucidal Activity

AbstractMethylene blue is an FDA (Food and Drug Administration) and EMA (European Medicines Agency) approved drug with an excellent safety profile. It displays broad-spectrum virucidal activity in the presence of UV light and has been shown to be effective in inactivating various viruses in blood products prior to transfusions. In addition, its use has been validated for methemoglobinemia and malaria treatment. In this study, we first evaluated the virucidal activity of methylene blue against influenza virus H1N1 upon different incubation times and in the presence or absence of light activation, and then against SARS-CoV-2. We further assessed the therapeutic activity of methylene blue by administering it to cells previously infected with SARS-CoV-2. Finally, we examined the effect of co-administration of the drug together with immune serum. Our findings reveal that methylene blue displays virucidal preventive or therapeutic activity against influenza virus H1N1 and SARS-CoV-2 at low micromolar concentrations and in the absence of UV-activation. We also confirm that MB antiviral activity is based on several mechanisms of action as the extent of genomic RNA degradation is higher in presence of light and after long exposure. Our work supports the interest of testing methylene blue in clinical studies to confirm a preventive and/or therapeutic efficacy against both influenza virus H1N1 and SARS-CoV-2 infections.

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Synthesis and in vitro Study of Antiviral and Virucidal Activity of Novel 2-[(4-Methyl-4H-1,2,4-triazol-3-yl)sulfanyl]acetamide Derivatives

Zeitschrift für Naturforschung C ◽

10.5560/znc.2011.66c0333 ◽

2011 ◽

Vol 66 ◽

pp. 0333

Author(s):

M. Wujec ◽

T. Plech ◽

A. Siwek ◽

B. Rajtar ◽

M. Polz-Dacewicz

Keyword(s):

In Vitro Study ◽

Vitro Study ◽

Virucidal Activity

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Impact of Different JAK Inhibitors and Methotrexate on Lymphocyte Proliferation and DNA Damage

Journal of Clinical Medicine ◽

10.3390/jcm10071431 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1431

Author(s):

Annika Reddig ◽

Linda Voss ◽

Karina Guttek ◽

Dirk Roggenbuck ◽

Eugen Feist ◽

...

Keyword(s):

Dna Damage ◽

Lymphocyte Proliferation ◽

Kinase Inhibitors ◽

Mononuclear Cells ◽

In Vitro Study ◽

Janus Kinase ◽

European Medicines Agency ◽

Peripheral Blood Mononuclear ◽

Dose Dependent

Janus kinase inhibitors (JAKis) represent a new strategy in rheumatoid arthritis (RA) therapy. Still, data directly comparing different JAKis are rare. In the present in vitro study, we investigated the immunomodulatory potential of four JAKis (tofacitinib, baricitinib, upadacitinib, and filgotinib) currently approved for RA treatment by the European Medicines Agency. Increasing concentrations of JAKi or methotrexate, conventionally used in RA therapy, were either added to freshly mitogen-stimulated or preactivated peripheral blood mononuclear cells (PBMC), isolated from healthy volunteers. A comparable, dose-dependent inhibition of lymphocyte proliferation was observed in samples treated with tofacitinib, baricitinib, and upadacitinib, while dosage of filgotinib had to be two orders of magnitude higher. In contrast, antiproliferative effects were strongly attenuated when JAKi were added to preactivated PBMCs. High dosage of upadacitinib and filgotinib also affected cell viability. Further, analyses of DNA double-strand break markers γH2AX and 53BP1 indicated an enhanced level of DNA damage in cells incubated with high concentrations of filgotinib and a dose-dependent reduction in clearance of radiation-induced γH2AX foci in the presence of tofacitinib or baricitinib. Thereby, our study demonstrated a broad comparability of immunomodulatory effects induced by different JAKi and provided first indications, that (pan)JAKi may impair DNA damage repair in irradiated PBMCs.

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

10.1101/2021.09.23.461483 ◽

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.

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