Direct virucidal effect of a throat lozenge with fixed combination of cetylpyridinium chloride and benzydamine hydrochloride on SARS-CoV-2 – in vitro study

Objectives. To evaluate the in vitro virucidal effect of the combination of cetylpyridinium chloride (CPC) and benzydamine hydrochloride (BH) as a throat lozenge against the novel SARS-CoV-2. Material and methods. The study evaluated the viral presence and titre in cell cultures by using SARS-CoV-2 virus incubated for 1, 5, 15 minutes, with three different concentrations of three different active substances (CPC, free BH/ CPC, BH/CPC lozenge). The titre of the virus was expressed as TCID50/ml calculated with the Spearman-Kärber method. Outcomes. The faster virucidal effect in high concentration was seen in the combination BH/CPC as throat lozenge when compared to CPC as free active substance. A reduction of the virus concentration was seen, at 15 minutes contact, in all three concentrations. Conclusions. There is a strong virucidal effect a throat lozenge with fixed combination of cetylpyridinium chloride and benzydamine hydrochloride on the novel coronavirus.

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A Throat Lozenge with Fixed Combination of Cetylpyridinium Chloride and Benzydamine Hydrochloride Has Direct Virucidal Effect on SARS-CoV-2

COVID ◽

10.3390/covid1020037 ◽

2021 ◽

Vol 1 (2) ◽

pp. 435-446

Author(s):

Andrej Steyer ◽

Miša Marušić ◽

Marko Kolenc ◽

Tina Triglav

Keyword(s):

Oral Cavity ◽

Active Substance ◽

Contact Time ◽

Fixed Combination ◽

Cetylpyridinium Chloride ◽

Virus Concentration ◽

Viral Titre ◽

Virucidal Effect ◽

Tract Infections ◽

Active Substances

Viruses are the most common causative agents of inflammation in the oral cavity and throat region. Most respiratory tract infections are self-limiting and require no specific treatment. However, patients often use different self-medication therapies that can treat both the symptoms and the cause. Throat lozenges with a fixed combination of benzydamine hydrochloride and cetypiridinium chloride (BH/CPC) have been shown to provide effective symptomatic relief for sore throat, but their effect on viruses has not been investigated to date. The antiseptic, cetylpyridinium chloride (CPC), has already been described as a successful bactericide. In addition, there are some studies suggesting its efficacy against certain enveloped viruses. Thus, the aim of our study was to examine the virucidal activity of CPC and a combination of BH/CPC as a free active substance or as lozenge on SARS-CoV-2 in vitro. Under in-laboratory simulated conditions of lozenge administration, we incubated SARS-CoV-2 with three different concentrations of each of the active substances, CPC, free BH/CPC or BH/CPC, as a lozenge suspension for 1 min, 5 min and 15 min of contact time. Infective viral particles were detected in cell cultures and the viral titre was calculated accordingly. Our results show that all active substances in high-concentration suspensions, as well as a medium concentration of the BH/CPC combination, exhibited a 4-log reduction in viral titre. Additionally, the highest concentration of BH/CPC as a lozenge had a faster virucidal effect compared to CPC as a free active substance alone, since a contact time as short as 1 min reduced the initial virus concentration by more than 4-log. This study demonstrates the effective strong virucidal effect of the lozenge, with the possibility of viral load reduction in the oral cavity and, consequently, reduced risk of viral transmission.

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The Antiviral and Antimalarial Drug Repurposing in Quest of Chemotherapeutics to Combat COVID-19 Utilizing Structure-Based Molecular Docking

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323999200824115536 ◽

2020 ◽

Vol 23 ◽

Author(s):

Sisir Nandi ◽

Mohit Kumar ◽

Mridula Saxena ◽

Anil Kumar Saxena

Keyword(s):

Molecular Docking ◽

In Silico ◽

Drug Repurposing ◽

Clinical Settings ◽

The Novel ◽

In Silico Docking ◽

Biochemical Mechanisms ◽

Novel Coronavirus ◽

In Silico Molecular Docking

Background: The novel coronavirus disease (COVID-19) is caused by a new strain (SARS-CoV-2) erupted in 2019. Nowadays, it is a great threat that claims uncountable lives worldwide. There is no specific chemotherapeutics developed yet to combat COVID-19. Therefore, scientists have been devoted in the quest of the medicine that can cure COVID- 19. Objective: Existing antivirals such as ASC09/ritonavir, lopinavir/ritonavir with or without umifenovir in combination with antimalarial chloroquine or hydroxychloroquine have been repurposed to fight the current coronavirus epidemic. But exact biochemical mechanisms of these drugs towards COVID-19 have not been discovered to date. Method: In-silico molecular docking can predict the mode of binding to sort out the existing chemotherapeutics having a potential affinity towards inhibition of the COVID-19 target. An attempt has been made in the present work to carry out docking analyses of 34 drugs including antivirals and antimalarials to explain explicitly the mode of interactions of these ligands towards the COVID-19protease target. Results: 13 compounds having good binding affinity have been predicted towards protease binding inhibition of COVID-19. Conclusion: Our in silico docking results have been confirmed by current reports from clinical settings through the citation of suitable experimental in vitro data available in the published literature.

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Synthetic and semi-synthetic drugs as promising therapeutic option for the treatment of COVID-19

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557520666201204162103 ◽

2020 ◽

Vol 20 ◽

Author(s):

Ekta Shirbhate ◽

Preeti Patel ◽

Vijay K Patel ◽

Ravichandran Veerasamy ◽

Prabodh C Sharma ◽

...

Keyword(s):

Therapeutic Option ◽

Antiviral Treatment ◽

The Novel ◽

Clinical Experiences ◽

Synthetic Compounds ◽

Synthetic Drugs ◽

Global Pandemic ◽

The World ◽

Novel Coronavirus

: The novel coronavirus disease-19 (COVID-19), a global pandemic that emerged from Wuhan, China has today travelled all around the world, so far 216 countries or territories with 21,732,472 people infected and 770,866 deaths globally (as per WHO COVID-19 update dated August 18, 2020). Continuous efforts are being made to repurpose the existing drugs and develop vaccines for combating this infection. Despite, to date, no certified antiviral treatment or vaccine prevails. Although, few candidates have displayed their efficacy in in vitro studies and are being repurposed for COVID-19 treatment. This article summarizes synthetic and semi-synthetic compounds displaying potent activity in their clinical experiences or studies against COVID-19 and also focuses on mode of action of drugs being repositioned against COVID-19.

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Direct antivirals working against the novel coronavirus: azithromycin (DAWn-AZITHRO), a randomized, multicenter, open-label, adaptive, proof-of-concept clinical trial of new antivirals working against SARS-CoV-2—azithromycin trial

Trials ◽

10.1186/s13063-021-05033-x ◽

2021 ◽

Vol 22 (1) ◽

Cited By ~ 1

Author(s):

Iwein Gyselinck ◽

◽

Laurens Liesenborghs ◽

Ewout Landeloos ◽

Ann Belmans ◽

...

Keyword(s):

Clinical Trial ◽

Standard Of Care ◽

Ordinal Scale ◽

Cytokine Signaling ◽

Nasopharyngeal Swab ◽

The Novel ◽

Proof Of Concept ◽

Open Label ◽

Novel Coronavirus

Abstract Background The rapid emergence and the high disease burden of the novel coronavirus SARS-CoV-2 have created a medical need for readily available drugs that can decrease viral replication or blunt the hyperinflammatory state leading to severe COVID-19 disease. Azithromycin is a macrolide antibiotic, known for its immunomodulatory properties. It has shown antiviral effect specifically against SARS-CoV-2 in vitro and acts on cytokine signaling pathways that have been implicated in COVID-19. Methods DAWn-AZITHRO is a randomized, open-label, phase 2 proof-of-concept, multicenter clinical trial, evaluating the safety and efficacy of azithromycin for treating hospitalized patients with COVID-19. It is part of a series of trials testing promising interventions for COVID-19, running in parallel and grouped under the name DAWn-studies. Patients hospitalized on dedicated COVID wards are eligible for study inclusion when they are symptomatic (i.e., clinical or radiological signs) and have been diagnosed with COVID-19 within the last 72 h through PCR (nasopharyngeal swab or bronchoalveolar lavage) or chest CT scan showing typical features of COVID-19 and without alternate diagnosis. Patients are block-randomized (9 patients) with a 2:1 allocation to receive azithromycin plus standard of care versus standard of care alone. Standard of care is mostly supportive, but may comprise hydroxychloroquine, up to the treating physician’s discretion and depending on local policy and national health regulations. The treatment group receives azithromycin qd 500 mg during the first 5 consecutive days after inclusion. The trial will include 284 patients and recruits from 15 centers across Belgium. The primary outcome is time from admission (day 0) to life discharge or to sustained clinical improvement, defined as an improvement of two points on the WHO 7-category ordinal scale sustained for at least 3 days. Discussion The trial investigates the urgent and still unmet global need for drugs that may impact the disease course of COVID-19. It will either provide support or else justify the discouragement of the current widespread, uncontrolled use of azithromycin in patients with COVID-19. The analogous design of other parallel trials of the DAWN consortium will amplify the chance of identifying successful treatment strategies and allow comparison of treatment effects within an identical clinical context. Trial registration EU Clinical trials register EudraCT Nb 2020-001614-38. Registered on 22 April 2020

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Characterization of the SARS-CoV-2 coronavirus X4-like accessory protein

Egyptian Journal of Medical Human Genetics ◽

10.1186/s43042-021-00160-1 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Olanrewaju Ayodeji Durojaye ◽

Nkwachukwu Oziamara Okoro ◽

Arome Solomon Odiba

Keyword(s):

Rapid Development ◽

Protein A ◽

The Novel ◽

Quality Model ◽

A Value ◽

Model Protein ◽

Novel Coronavirus ◽

Global Threat

Abstract Background The novel coronavirus SARS-CoV-2 is currently a global threat to health and economies. Therapeutics and vaccines are in rapid development; however, none of these therapeutics are considered as absolute cure, and the potential to mutate makes it necessary to find therapeutics that target a highly conserved regions of the viral structure. Results In this study, we characterized an essential but poorly understood coronavirus accessory X4 protein, a core and stable component of the SARS-CoV family. Sequence analysis shows a conserved ~ 90% identity between the SARS-CoV-2 and previously characterized X4 protein in the database. QMEAN Z score of the model protein shows a value of around 0.5, within the acceptable range 0–1. A MolProbity score of 2.96 was obtained for the model protein and indicates a good quality model. The model has Ramachandran values of φ = − 57o and ψ = − 47o for α-helices and values of φ = − 130o and ψ = + 140o for twisted sheets. Conclusions The protein data obtained from this study provides robust information for further in vitro and in vivo experiment, targeted at devising therapeutics against the virus. Phylogenetic analysis further supports previous evidence that the SARS-CoV-2 is positioned with the SL-CoVZC45, BtRs-BetaCoV/YN2018B and the RS4231 Bat SARS-like corona viruses.

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Comparison of Four SARS-CoV-2 Neutralization Assays

Vaccines ◽

10.3390/vaccines9010013 ◽

2020 ◽

Vol 9 (1) ◽

pp. 13

Author(s):

Lydia Riepler ◽

Annika Rössler ◽

Albert Falch ◽

André Volland ◽

Wegene Borena ◽

...

Keyword(s):

Vesicular Stomatitis Virus ◽

Neutralizing Antibodies ◽

The Other ◽

In Vitro Assays ◽

The Novel ◽

Effective Protection ◽

Vaccine Candidates ◽

Vesicular Stomatitis ◽

Novel Coronavirus

Neutralizing antibodies are a major correlate of protection for many viruses including the novel coronavirus SARS-CoV-2. Thus, vaccine candidates should potently induce neutralizing antibodies to render effective protection from infection. A variety of in vitro assays for the detection of SARS-CoV-2 neutralizing antibodies has been described. However, validation of the different assays against each other is important to allow comparison of different studies. Here, we compared four different SARS-CoV-2 neutralization assays using the same set of patient samples. Two assays used replication competent SARS-CoV-2, a focus forming assay and a TCID50-based assay, while the other two assays used replication defective lentiviral or vesicular stomatitis virus (VSV)-based particles pseudotyped with SARS-CoV-2 spike. All assays were robust and produced highly reproducible neutralization titers. Titers of neutralizing antibodies correlated well between the different assays and with the titers of SARS-CoV-2 S-protein binding antibodies detected in an ELISA. Our study showed that commonly used SARS-CoV-2 neutralization assays are robust and that results obtained with different assays are comparable.

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Leakage of Endotoxins through the Endotoxin Retentive Filter: An in vitro Study

Blood Purification ◽

10.1159/000520792 ◽

2022 ◽

pp. 1-9

Author(s):

Hiroshi Nozaki ◽

Yoshihiro Tange ◽

Yoji Inada ◽

Takashi Uchino ◽

Nakanobu Azuma

Keyword(s):

Sodium Hypochlorite ◽

Peracetic Acid ◽

In Vitro Study ◽

Dialysis Fluid ◽

High Concentration ◽

Membrane Pores ◽

Polyether Sulfone ◽

Repeated Use ◽

High Concentrations

Introduction: Ultrapurification of dialysis fluid has enabled highly efficient dialysis treatments. Online hemodiafiltration is one such treatment that uses a purified dialysis fluid as a supplemental fluid. In this method, an endotoxin retentive filter (ETRF) is used in the final step of dialysis fluid purification, with the aim of preventing leakage of endotoxins. Sodium hypochlorite and peracetic acid are used as disinfecting agents for the dialysis fluid pipes containing the ETRF; however, the effects of these agents on ETRF membrane pores have not been fully clarified. Methods: Water permeability (flux) and endotoxin permeability were assessed in 3 types of ETRFs made with different membrane materials: polyester polymer alloy (PEPA), polyether sulfone (PES), and polysulfone (PS). High-concentration sodium hypochlorite and 2 types of peracetic acid were used as disinfecting agents, and the changes in flux and the endotoxin sieving coefficient (SC) were measured. Results: After repeated use of high concentrations of sodium hypochlorite and peracetic acid, the PEPA and PES ETRFs did not permit passage of endotoxins, regardless of their flux. However, in the PS ETRF, the flux and endotoxin SC increased with the number of cleaning cycles. No differences were observed according to the concentration of peracetic acid disinfecting agents. Conclusion: PEPA and PES ETRFs completely prevent endotoxin leakage and can be disinfected at concentrations higher than the conventionally recommended concentration without affecting pore expansion. Even new PS ETRFs have low levels of endotoxin leakage, which increase after disinfection cycles using sodium hypochlorite and peracetic acid.

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Determination of the maximum inhibitory dilution of cetylpyridinium chloride-based mouthwashes against staphylococcus aureus: an in vitro study

Journal of Applied Oral Science ◽

10.1590/s1678-77572008000400009 ◽

2008 ◽

Vol 16 (4) ◽

pp. 275-279 ◽

Cited By ~ 15

Author(s):

Evandro Watanabe ◽

Juliane Maria Guerreiro Tanomaru ◽

Andresa Piacezzi Nascimento ◽

Fumio Matoba-Júnior ◽

Mario Tanomaru-Filho ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Cetylpyridinium Chloride ◽

In Vitro Study ◽

Vitro Study

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Evaluation of Sealing Materials Adhesion to Enamel An in vitro study

Materiale Plastice ◽

10.37358/mp.17.1.4801 ◽

2017 ◽

Vol 54 (1) ◽

pp. 129-132

Author(s):

Andreea Simona Pop ◽

Radu Septimiu Campian ◽

Mariana Pacurar ◽

Elina Teodorescu ◽

Olimpia Bunta ◽

...

Keyword(s):

In Vitro Study ◽

Specific Method ◽

High Concentration ◽

Posterior Teeth ◽

Inorganic Particles ◽

Material Homogeneity ◽

Materials Used ◽

High Degree ◽

Pits And Fissures

Sealing the pits and fissures of posterior teeth represents a local and specific method of caries prevention. The aim of this study was to evaluate the adhesion of two materials used in sealing pits and fissures: Pitt and Fisure and Fissurit FX (Voco), with the help of the scanning electronic microscope (SEM). The results of the study revealed a much higher quality of the Fissurit FX (Voco) product both in terms of adhesion to the enamel and material homogeneity. The Pitt and Fisure product showed a high degree of detachment from the enamel, marginal infiltration, large particles and a high concentration of inorganic particles.

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