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1.
Appl Environ Microbiol ; 90(2): e0201023, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38193683

RESUMO

Expulsions of virus-laden aerosols or droplets from the oral and nasal cavities of an infected host are an important source of onward respiratory virus transmission. However, the presence of infectious influenza virus in the oral cavity during infection has not been widely considered, and thus, little work has explored the environmental persistence of influenza virus in oral cavity expulsions. Using the ferret model, we detected infectious virus in the nasal and oral cavities, suggesting that the virus can be expelled into the environment from both anatomical sites. We also assessed the stability of two influenza A viruses (H1N1 and H3N2) in droplets of human saliva or respiratory mucus over a range of relative humidities. We observed that influenza virus infectivity decays rapidly in saliva droplets at intermediate relative humidity, while viruses in airway surface liquid droplets retain infectivity. Virus inactivation was not associated with bulk protein content, salt content, or droplet drying time. Instead, we found that saliva droplets exhibited distinct inactivation kinetics during the wet and dry phases at intermediate relative humidity, and droplet residue morphology may lead to the elevated first-order inactivation rate observed during the dry phase. Additionally, distinct differences in crystalline structure and nanobead localization were observed between saliva and airway surface liquid droplets. Together, our work demonstrates that different respiratory fluids exhibit unique virus persistence profiles and suggests that influenza viruses expelled from the oral cavity may contribute to virus transmission in low- and high-humidity environments.IMPORTANCEDetermining how long viruses persist in the environment is important for mitigating transmission risk. Expelled infectious droplets and aerosols are composed of respiratory fluids, including saliva and complex mucus mixtures, but how well influenza viruses survive in such fluids is largely unknown. Here, we find that infectious influenza virus is present in the oral cavity of infected ferrets, suggesting that saliva-containing expulsions can play a role in onward transmission. Additionally, influenza virus in droplets composed of saliva degrades more rapidly than virus within respiratory mucus. Droplet composition impacts the crystalline structure and virus localization in dried droplets. These results suggest that viruses from distinct sites in the respiratory tract could have variable persistence in the environment, which will impact viral transmission fitness.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Animais , Humanos , Umidade , Vírus da Influenza A Subtipo H1N1/fisiologia , Saliva , Vírus da Influenza A Subtipo H3N2/fisiologia , Estações do Ano , Furões , Muco , Aerossóis
2.
Biologicals ; 85: 101751, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38387156

RESUMO

Viral clearance steps are routinely included in monoclonal antibody purification processes to safeguard product from potential virus contamination. These steps are often experimentally studied using product-specific feeds and parameters for each project to demonstrate viral clearance capability. However, published evidence suggests that viral clearance capability of many of these steps are not significantly impacted by variations in feed material or process parameter within commonly used ranges. The current investigation confirms robust retrovirus inactivation by low pH treatment and parvovirus removal by second-generation virus filters, independent to individual antibody molecules. Our results also reveal robust retrovirus removal by flowthrough anion exchange chromatography, inside the limits of protein load and host cell protein content. The cumulative viral clearance capability from these steps leads to an excess clearance safety factor of 10,000-fold for endogenous retrovirus-like particles. These results further justify the use of prior knowledge-based modular viral clearance estimation as opposed to repetitive experimentation.


Assuntos
Retrovirus Endógenos , Parvovirus , Vírus , Anticorpos Monoclonais , Filtração
3.
J Med Virol ; 95(12): e29261, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38054557

RESUMO

The monkeypox virus (MPXV) outbreak in 2022 has renewed interest in the detection of antibodies against orthopox viruses (OPXV) and MPXV, as serological methods can aid diagnostics and are key to epidemiological studies. Here three complementary serological methods are described with different strengths to aid the development and evaluation of in-house assays: An immunofluorescence assay (IFA) for specific detection of IgG and IgM, an enzyme-linked immunosorbent assay for higher sample throughput to aid epidemiological studies and a neutralization test to detect virus neutralizing antibodies. As implementation of MPXV-specific diagnostics is often hampered by the requirement for a dedicated biosafety level 3 laboratory (BSL-3), the focus of this study is on biosafety aspects to facilitate safe testing also under BSL-2 conditions. To this aim, it was analyzed whether OPXV, which can be handled under BSL-2 conditions, could be used as less virulent alternatives to MPXV. Furthermore, an inactivation method was established to remove up to five log-steps of infectious virus particles from viraemic sera without compromising antibody detection. The results show that immunological cross-reactivity between OPXV provides an opportunity for the interchangeable usage of different OPXV species in serological assays, enabling MPXV serology outside of BSL-3 facilities.


Assuntos
Contenção de Riscos Biológicos , Monkeypox virus , Humanos , Laboratórios , Anticorpos Antivirais , Testes de Neutralização
4.
J Med Virol ; 95(1): e28287, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36345579

RESUMO

Respiratory syncytial virus (RSV) is the most important virus that causes lower respiratory tract disease in children; efficient viral identification is an important component of disease prevention and treatment. Here, we developed and evaluated a ready-to-use (RTU) nucleic acid extraction-free direct reagent for identification of RSV (RTU-Direct test) in clinical samples. The limit of detection (LOD) of the RSV RTU-Direct test was consistent with the LOD of the standard test using extracted nucleic acids. The virus inactivation ability of RTU-Direct reagent was confirmed by viral infectivity assays involving RTU-Direct-treated samples containing RSV and human coronavirus OC43. RSV RNA stability was significantly better in RTU-Direct reagent than in conventional virus transport medium (VTM) at room temperature and 4°C (p < 0.05). The clinical performance of the RTU-Direct test was evaluated using 155 respiratory specimens from patients with suspected RSV infection. Positive agreement between the RTU-Direct test and the VTM standard test was 100% (42/42); negative agreement was 99.1% (112/113), and the kappa statistic was 0.968 (p < 0.001). The distributions of Ct values did not significantly differ between the RTU-Direct test and the standard test (p > 0.05). Overall, the RTU-Direct reagent can improve the efficiency and biosafety of RSV detection, while reducing the cost of detection.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Criança , Humanos , Indicadores e Reagentes , Contenção de Riscos Biológicos , Sensibilidade e Especificidade , Vírus Sincicial Respiratório Humano/genética , Infecções por Vírus Respiratório Sincicial/diagnóstico , Nasofaringe
5.
Trop Med Int Health ; 28(4): 262-274, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36806816

RESUMO

OBJECTIVE: Arboviruses are emerging as a relevant threat to transfusion safety. Pathogen inactivation methods (PIMs) may reduce the risk of transmission through transfusion, as long as they meet minimum standards for effectiveness. This study aims to assess the log reduction of viral load achieved with different PIMs, according to the blood product they are used on and the arbovirus targeted. METHODS: Systematic literature review and meta-analysis. Searches were conducted in MEDLINE and Embase. The study protocol was registered in PROSPERO CRD42022312061. We selected records reporting the log reduction of viral load achieved with the main PIMs (amotosalen + UVA light [INTERCEPT], riboflavin + UV light [Mirasol], methylene blue + visible light/UVC light [THERAFLEX], solvent detergent, amustaline [INTERCEPT] and PEN110 [Inactine]), applied to any blood product (plasma, platelets, red blood cells or whole blood) and for any arbovirus. The log reduction of viral loads was assessed by obtaining the mean log reduction factor (LRF). We compared and classified the LRF of different techniques using statistical methods. RESULTS: We included 59 publications reporting LRF results in 17 arboviruses. For 13 arboviruses, including Chikungunya virus, Dengue virus, West Nile virus and Zika virus, at least one of the methods achieves adequate or optimal log reduction of viral load-mean LRF ≥4. The LRF achieved with riboflavin + UV light is inferior to the rest of the techniques, both overall and specifically for plasma, platelets preserved in platelet additive solution (PAS)/plasma, and red blood cells/whole blood. The LRF achieved using Mirasol is also lower for inactivating Chikungunya virus, Dengue virus and Zika virus. For West Nile virus, we found no significant differences. In plasma, the method that achieves the highest LRF is solvent/detergent; in platelets, THERAFLEX and INTERCEPT; and in red blood cells/whole blood, PEN110 (Inactine). CONCLUSION: Not all PIMs achieve the same LRF, nor is this equivalent between the different arboviruses or blood products. Overall, the LRFs achieved using riboflavin + UV light (Mirasol) are inferior to those achieved with the rest of the PIMs. Regarding the others, LRFs vary by arbovirus and blood product. In light of the threat of different arboviruses, blood establishments should have already validated PIMs and be logistically prepared to implement these techniques quickly.


Assuntos
Arbovírus , Infecção por Zika virus , Zika virus , Humanos , Detergentes , Poliaminas , Riboflavina
6.
Virol J ; 20(1): 221, 2023 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-37789354

RESUMO

BACKGROUND: The live-attenuated Rift Valley Fever Smithburn (SB) vaccine is one of the oldest products widely used in ruminants for control of RVF infections. Vaccinations with RVF Smithburn result in residual pathogenic effect and is limited for use in non-pregnant animals. Commercially available RVFV inactivated vaccines are considered safer options to control the disease. These products are prepared from virulent RVFV isolates and present occupational safety concerns. This research study evaluates the ability of an inactivated SB vaccine strain to elicit neutralising antibody response in sheep. METHODS: The RVF Smithburn vaccine was inactivated with binary ethylenimine at 37 °C. Inactivated RVFV cultures were adjuvanted with Montande™ Gel-01 and aluminium hydroxide (Al (OH)3) gel for immunogenicity and safety determination in sheep. The commercial RVF inactivated vaccine and a placebo were included as positive and negative control groups, respectively. RESULTS: Inactivated RVFV vaccine formulations were safe with all animals showing no clinical signs of RVFV infection and temperature reactions following prime-boost injections. The aluminium hydroxide formulated vaccine induced an immune response as early as 14 days post primary vaccination with neutralising antibody titre of 1:20 and a peak antibody titre of 1:83 was reached on day 56. A similar trend was observed in the animal group vaccinated with the commercial inactivated RVF vaccine obtaining the highest antibody titre of 1:128 on day 56. The neutralizing antibody levels remained within a threshold for the duration of the study. Merino sheep vaccinated with Montanide™ Gel-01-Smithburn were characterised with overall lower immune response when compared to aluminium hydroxide vaccine emulsions. CONCLUSIONS: These finding suggests that the inactivated RVF Smithburn vaccine strain adjuvanted with aluminium-hydroxide can be used an alternative to the products prepared from virulent RVFV isolates for protection of ruminants against the disease. The vaccine can further be evaluated for safety in pregnant ewes.


Assuntos
Febre do Vale de Rift , Vírus da Febre do Vale do Rift , Doenças dos Ovinos , Vacinas Virais , Animais , Feminino , Hidróxido de Alumínio , Anticorpos Neutralizantes , Anticorpos Antivirais , Febre do Vale de Rift/prevenção & controle , Ruminantes , Ovinos , Doenças dos Ovinos/prevenção & controle , Vacinas Atenuadas , Vacinas de Produtos Inativados/efeitos adversos
7.
Biotechnol Bioeng ; 120(6): 1605-1613, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36924035

RESUMO

In the production of monoclonal antibodies (mAbs) intended for use in humans, it is a global regulatory requirement that the manufacturing process includes unit operations that are proven to inactivate or remove adventitious agents to ensure viral safety. Viral inactivation by low pH hold (LPH) is typically used to ensure this viral safety in the purification process of mAbs and other biotherapeutics derived from mammalian cell lines. To ascertain the effectiveness of the LPH step, viral clearance studies have evaluated LPH under worst-case conditions of pH above the manufacturing set point and hold duration at or below the manufacturing minimum. Highly acidic conditions (i.e., pH < 3.60) provide robust and effective enveloped virus inactivation but may lead to reduced product quality of the therapeutic protein. However, when viral inactivation is operated above pH 3.60 to ensure product stability, effective (>4 log10 reduction factor) viral inactivation may not be observed under these worst-case pH conditions in viral clearance studies. A multivariate design of experiments was conducted to further characterize the operating space for low pH viral inactivation of a model retrovirus, xenotropic murine leukemia virus (X-MuLV). The statistically designed experiment evaluated the effect of mAb isotype, pH, temperature, acid titrant, sodium chloride (NaCl) concentration, virus spike timing, and post-spike filtration on X-MuLV inactivation. Data from the characterization study were used to generate predictive models to identify conditions that reliably achieve effective viral inactivation at pH ≥ 3.60. Results of the study demonstrated that NaCl concentration has the greatest effect on virus inactivation in the range studied, and pH has a large effect when the load material has no additional NaCl. Overall, robust and effective inactivation of X-MuLV at pH 3.65-3.80 can be achieved by manipulating either the pH or the NaCl concentration of the load material. This study contributes to the understanding of ionic strength as an influential parameter in low pH viral inactivation studies.


Assuntos
Anticorpos Monoclonais , Cloreto de Sódio , Animais , Camundongos , Humanos , Vírus da Leucemia Murina/química , Inativação de Vírus , Concentração de Íons de Hidrogênio , Concentração Osmolar , Mamíferos/metabolismo
8.
Bioessays ; 43(6): e2000312, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33857328

RESUMO

Biocidal agents such as formaldehyde and glutaraldehyde are able to inactivate several coronaviruses including SARS-CoV-2. In this article, an insight into one mechanism for the inactivation of these viruses by those two agents is presented, based on analysis of previous observations during electron microscopic examination of several members of the orthocoronavirinae subfamily, including the new virus SARS-CoV-2. This inactivation is proposed to occur through Schiff base reaction-induced conformational changes in the spike glycoprotein leading to its disruption or breakage, which can prevent binding of the virus to cellular receptors. Also, a new prophylactic and therapeutic measure against SARS-CoV-2 using acetoacetate is proposed, suggesting that it could similarly break the viral spike through Schiff base reaction with lysines of the spike protein. This measure needs to be confirmed experimentally before consideration. In addition, a new line of research is proposed to help find a broad-spectrum antivirus against several members of this subfamily.


Assuntos
Desinfetantes/farmacologia , Corpos Cetônicos/farmacologia , SARS-CoV-2/efeitos dos fármacos , Glicoproteína da Espícula de Coronavírus/metabolismo , Animais , Antivirais/química , Antivirais/farmacologia , Desinfetantes/química , Formaldeído/química , Formaldeído/farmacologia , Glutaral/química , Glutaral/farmacologia , Humanos , Corpos Cetônicos/química , Corpos Cetônicos/metabolismo , Cetose/etiologia , Cetose/virologia , SARS-CoV-2/patogenicidade , Vírion/efeitos dos fármacos , Vírion/patogenicidade
9.
J Invertebr Pathol ; 201: 108023, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37995901

RESUMO

The effects of chemical factors on the infectivity of DIV1 have not been fully accessed yet. In order to investigate the stability of DIV1 to strong brine, pH, and other chemical conditions, we conducted a bioassay using clinically healthy Penaeus vannamei individuals. DIV1 inoculum was exposed to various chemical conditions, and the infectivity of DIV1 was determined through intramuscular injection. The results showed that DIV1 lost its infectivity when exposed to strong brine, specifically in a 3 mol/L NaCl solution for a duration of 1 h. Moreover, DIV1 was found to be inactivated within 1 h when subjected to pH levels below 3.1 or above 9.6. Additionally, both Triton X-100 and 1 % formaldehyde demonstrated the ability to inactivate DIV1. These results provide valuable insights into the tolerance of DIV1 towards certain chemical factors, serving as a reference for the establishment of biosecurity measures against DIV1.


Assuntos
Penaeidae , Animais , Octoxinol , Injeções Intramusculares
10.
Risk Anal ; 2023 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-36973964

RESUMO

Exploring transmission risk of different routes has major implications for epidemic control. However, disciplinary boundaries have impeded the dissemination of epidemic information, have caused public panic about "air transmission," "air-conditioning transmission," and "environment-to-human transmission," and have triggered "hygiene theater." Animal experiments provide experimental evidence for virus transmission, but more attention is paid to whether transmission is driven by droplets or aerosols and using the dichotomy to describe most transmission events. Here, according to characteristics of experiment setups, combined with patterns of human social interactions, we reviewed and grouped animal transmission experiments into four categories-close contact, short-range, fomite, and aerosol exposure experiments-and provided enlightenment, with experimental evidence, on the transmission risk of severe acute respiratory syndrome coronavirus (SARS-COV-2) in humans via different routes. When referring to "air transmission," context should be showed in elaboration results, rather than whether close contact, short or long range is uniformly described as "air transmission." Close contact and short range are the major routes. When face-to-face, unprotected, horizontally directional airflow does promote transmission, due to virus decay and dilution in air, the probability of "air conditioning transmission" is low; the risk of "environment-to-human transmission" highly relies on surface contamination and human behavior based on indirect path of "fomite-hand-mucosa or conjunctiva" and virus decay on surfaces. Thus, when discussing the transmission risk of SARS-CoV-2, we should comprehensively consider the biological basis of virus transmission, environmental conditions, and virus decay. Otherwise, risk of certain transmission routes, such as long-range and fomite transmission, will be overrated, causing public excessive panic, triggering ineffective actions, and wasting epidemic prevention resources.

11.
Int J Mol Sci ; 24(9)2023 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-37175626

RESUMO

For decades, the ability of detergents to solubilize biological membranes has been utilized in biotechnological manufacturing to disrupt the lipid envelope of potentially contaminating viruses and thus enhance the safety margins of plasma- and cell-derived drugs. This ability has been linked to detergent micelles, which are formed if the concentration of detergent molecules exceeds the critical micelle concentration (CMC). Traditionally, the CMC of detergents is determined in deionized water (ddH2O), i.e., a situation considerably different from the actual situation of biotechnological manufacturing. This study compared, for five distinct detergents, the CMC in ddH2O side-by-side with two biopharmaceutical process intermediates relevant to plasma-derived (Immunoglobulin) and cell-derived (monoclonal antibody) products, respectively. Depending on the matrix, the CMC of detergents changed by a factor of up to ~4-fold. Further, the CMC in biotechnological matrices did not correlate with antiviral potency, as Triton X-100 (TX-100) and similar detergents had comparatively higher CMCs than polysorbate-based detergents, which are known to be less potent in terms of virus inactivation. Finally, it was demonstrated that TX-100 and similar detergents also have virus-inactivating properties if applied below the CMC. Thus, the presence of detergent micelles might not be an absolute prerequisite for the disruption of virus envelopes.


Assuntos
Detergentes , Vírus , Detergentes/farmacologia , Micelas , Inativação de Vírus , Octoxinol/farmacologia
12.
J Infect Dis ; 225(4): 587-592, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34904659

RESUMO

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) since 2019 has made mask-wearing, physical distancing, hygiene, and disinfection complementary measures to control virus transmission. Especially for health facilities, we evaluated the efficacy of an UV-C autonomous robot to inactivate SARS-CoV-2 desiccated on potentially contaminated surfaces. ASSUM (autonomous sanitary sterilization ultraviolet machine) robot was used in an experimental box simulating a hospital intensive care unit room. Desiccated SARS-CoV-2 samples were exposed to UV-C in 2 independent runs of 5, 12, and 20 minutes. Residual virus was eluted from surfaces and viral titration was carried out in Vero E6 cells. ASSUM inactivated SARS-CoV-2 by ≥ 99.91% to ≥ 99.99% titer reduction with 12 minutes or longer of UV-C exposure and onwards and a minimum distance of 100cm between the device and the SARS-CoV-2 desiccated samples. This study demonstrates that ASSUM UV-C device is able to inactivate SARS-CoV-2 within a few minutes.


Assuntos
COVID-19 , Robótica , SARS-CoV-2/efeitos da radiação , Esterilização/métodos , Raios Ultravioleta , Inativação de Vírus/efeitos da radiação , COVID-19/prevenção & controle , Hospitais , Humanos
13.
Transfusion ; 62(12): 2454-2457, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36146943

RESUMO

BACKGROUND: The currently ongoing outbreak of monkeypox virus in many non-endemic countries around the world has also raised concerns about the safety of plasma-derived medicinal products. Based on what is known about the poxviridae, that is, that members are exceedingly large and carry a lipid envelope, effective removal and inactivation by plasma product manufacturing processes is expected. For the widely used solvent-detergent (S/D) treatments, however, poxviruses have been reported as potentially being a bit more resistant. STUDY DESIGN AND METHODS: Using a S/D mixture comprising tri-n-butyl-phosphate, polysorbate 80 and Triton X-100 (TX-100), inactivation of vaccinia virus (a model closely resembling monkeypox virus, both within the same genus, i.e., Orthopoxvirus) in a plasma-derived process intermediate was analyzed over 60 min. As use of Triton X-100 will, based on environmental concerns, be restricted, similar experiments were conducted with a physicochemically virtually identical alternative, Nereid. RESULTS: Fast inactivation of vaccinia virus to the assay detection limit, that is, reduction of infectivity by greater than 4 log10 within 10-20 min, was measured for the TX-100 S/D mixture. The alternative S/D mixture (Nereid instead of TX-100) was found fully equivalent. CONCLUSION: As for other lipid-enveloped viruses, treatment of process intermediates with S/D mixtures containing TX-100 or the closely related detergent Nereid are highly effective in inactivating poxviruses. Thus, the current spread of monkeypox virus does not compromise the viral safety margins of plasma-derived medicines.


Assuntos
Vírus , Humanos , Solventes , Lipídeos
14.
Virol J ; 19(1): 29, 2022 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-35144624

RESUMO

Ultraviolet (UV) light has previously been established as useful method of disinfection, with demonstrated efficacy to inactivate a broad range of microorganisms. The advent of ultraviolet light-emitting diodes provides advantages in ease of disinfection, in that there can be delivery of germicidal UV with the same light unit that delivers standard white light to illuminate a room. Herein we demonstrate the efficacy and feasibility of ultraviolet light-emitting diodes as a means of decontamination by inactivating two distinct virus models, human coronavirus 229E and human immunodeficiency virus. Importantly, the same dose of ultraviolet light that inactivated human viruses also elicited complete inactivation of ultraviolet-resistant bacterial spores (Bacillus pumilus), a gold standard for demonstrating ultraviolet-mediated disinfection. This work demonstrates that seconds of ultraviolet light-emitting diodes (UV-LED) exposure can inactivate viruses and bacteria, highlighting that UV-LED could be a useful and practical tool for broad sanitization of public spaces.


Assuntos
Coronavirus Humano 229E , Desinfecção , HIV-1 , Raios Ultravioleta , Inativação de Vírus/efeitos da radiação , Coronavirus Humano 229E/efeitos da radiação , Desinfecção/métodos , HIV-1/efeitos da radiação , Humanos
15.
Biotechnol Bioeng ; 119(4): 1091-1104, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35023152

RESUMO

Detergent-mediated virus inactivation (VI) provides a valuable orthogonal strategy for viral clearance in mammalian processes, in particular for next-generation continuous manufacturing. Furthermore, there exists an industry-wide need to replace the conventionally employed detergent Triton X-100 with eco-friendly alternatives. However, given Triton X-100 has been the gold standard for VI due its minimal impact on protein stability and high inactivation efficacy, inactivation by other eco-friendly detergents and its impact on protein stability is not well understood. In this study, the sugar-based detergent commonly used in membrane protein purification, n-dodecyl-ß- d-maltoside was found to be a promising alternative for VI. We investigated a panel of detergents to compare the relative VI efficacy, impact on therapeutic quality attributes, and clearance of the VI agent and other impurities through subsequent chromatographic steps. Detergent-mediated inactivation and protein stability showed comparable trends to low pH inactivation. Using experimental and modeling data, we found detergent-mediated product aggregation and its kinetics to be driven by extrinsic factors such as detergent and protein concentration. Detergent-mediated aggregation was also impacted by an initial aggregation level as well as intrinsic factors such as the protein sequence and detergent hydrophobicity, and critical micelle concentration. Knowledge gained here on factors driving product stability and VI provides valuable insight to design, standardize, and optimize conditions (concentration and duration of inactivation) for screening of detergent-mediated VI.


Assuntos
Produtos Biológicos , Inativação de Vírus , Animais , Detergentes/química , Cinética , Mamíferos , Octoxinol/química , Estabilidade Proteica
16.
Int J Mol Sci ; 23(2)2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35055053

RESUMO

Triton X-100 (TX-100) is a widely used detergent to prevent viral contamination of manufactured biologicals and biopharmaceuticals, and acts by disrupting membrane-enveloped virus particles. However, environmental concerns about ecotoxic byproducts are leading to TX-100 phase out and there is an outstanding need to identify functionally equivalent detergents that can potentially replace TX-100. To date, a few detergent candidates have been identified based on viral inactivation studies, while direct mechanistic comparison of TX-100 and potential replacements from a biophysical interaction perspective is warranted. Herein, we employed a supported lipid bilayer (SLB) platform to comparatively evaluate the membrane-disruptive properties of TX-100 and a potential replacement, Simulsol SL 11W (SL-11W), and identified key mechanistic differences in terms of how the two detergents interact with phospholipid membranes. Quartz crystal microbalance-dissipation (QCM-D) measurements revealed that TX-100 was more potent and induced rapid, irreversible, and complete membrane solubilization, whereas SL-11W caused more gradual, reversible membrane budding and did not induce extensive membrane solubilization. The results further demonstrated that TX-100 and SL-11W both exhibit concentration-dependent interaction behaviors and were only active at or above their respective critical micelle concentration (CMC) values. Collectively, our findings demonstrate that TX-100 and SL-11W have distinct membrane-disruptive effects in terms of potency, mechanism of action, and interaction kinetics, and the SLB platform approach can support the development of biophysical assays to efficiently test potential TX-100 replacements.


Assuntos
Membrana Celular/classificação , Membrana Celular/efeitos dos fármacos , Detergentes/química , Detergentes/farmacologia , Bicamadas Lipídicas/química , Octoxinol/química , Octoxinol/farmacologia , Fenômenos Químicos , Estrutura Molecular , Análise Espectral
17.
J Environ Manage ; 308: 114617, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35121465

RESUMO

Nanotechnology holds huge potential for the prevention of various viral outbreaks that have increased at a disquieting rate over the past decades. Metal oxide nanomaterials with oxidative capability are the effective materials that provide platforms as well as tools for the well understanding of the mechanism, its detection, and treatment of various viral diseases like measles, influenza, herpes, ebola, current COVID-19 etc. In this inclusive review, we survey various previous research articles on different notable photoactive transition metal oxides that possess enough potential to act as antiviral agents for the deactivation of harmful viruses. We investigated and highlighted the plausible photocatalytic oxidative mechanism of photoactive transition metal oxides in degrading viral coatings, genomic RNA using suitable free radical generation. The key finding of the present review article including the discovery of a vision on the suitable photocatalytic transition metal oxides that have been proven to be excellent against harmful viruses and consequently combatting deadly CoV-2 in the environment. This review intends to provide conclusive remarks and a realistic outlook on other advanced photocatalytic metal oxides as a potential solution in battling other similar upcoming pandemics.


Assuntos
COVID-19 , Vírus , Desinfecção , Humanos , Óxidos , SARS-CoV-2
18.
BMC Oral Health ; 22(1): 47, 2022 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-35216566

RESUMO

BACKGROUND: Healthcare professionals, especially dentists and dental hygienists, are at increased risk for contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through air-borne particles and splatter. This study assessed the in vitro virucidal activity of 0.5% (w/v) povidone-iodine (PVP-I) oral rinse against SARS-CoV-2 to demonstrate its utility as a professional oral rinse. METHODS: A 0.5% (w/v) PVP-I oral rinse formulation, placebo oral rinse, and positive (70% [v/v] ethanol and water) and negative (water) controls were assessed using the time-kill method. SARS-CoV-2 was propagated in Vero 76 host cells. Following neutralization validation, triplicate tests were performed for each test formulation and virucidal activity measured at 15, 30, and 60 s and 5 min. RESULTS: The 0.5% (w/v) PVP-I oral rinse demonstrated effective in vitro virucidal activity against SARS-CoV-2 as early as 15 s after exposure; viral titer was reduced to < 0.67 log10 50% cell culture infectious dose (CCID50)/0.1 mL (log10 reduction of > 4.0) at 30 s, whereas the placebo oral rinse reduced the SARS-CoV-2 viral titer to 4.67 and 4.5 log10 CCID50/0.1 mL at the 15- and 30-s time points, with a log10 reduction of 0.63 and 0.17, respectively. No toxicity or cytotoxic effects against Vero 76 host cells were observed with the 0.5% (w/v) PVP-I oral rinse; positive and negative controls performed as expected. CONCLUSIONS: In vitro virucidal activity of 0.5% (w/v) PVP-I oral rinse against SARS-CoV-2 was demonstrated. Rapid inactivation of SARS-CoV-2 was observed with 0.5% (w/v) formulation with a contact duration of 15 s. Clinical investigations are needed to assess the effectiveness of PVP-I oral rinse against SARS-CoV-2 in dental practice.


Assuntos
COVID-19 , Povidona-Iodo , Humanos , Antissépticos Bucais/farmacologia , Povidona-Iodo/farmacologia , SARS-CoV-2
19.
Artigo em Alemão | MEDLINE | ID: mdl-34982174

RESUMO

The hepatitis E virus (HEV) is an etiological agent of acute hepatitis in humans. In addition, chronic infections resulting in fatal liver cirrhosis currently emerge in immunosuppressed transplant patients. The number of notified hepatitis E cases in Germany has steeply increased in recent years. Here, genotype 3, which can be zoonotically transmitted from animals to humans, is predominant. The main reservoirs are pigs and wild boars, which show no signs of infection. In this article, the distribution of HEV in animals in Germany, possible transmission pathways, and especially the importance of food as a transmission vehicle are presented based on the current scientific literature.HEV is widely spread among domestic pigs and wild boars in Germany and the virus is mainly transmitted by direct contact or by consumption of food produced from those animals. However, if HEV RNA is detected in specific food it is often unclear whether the contained virus is still infectious or inactivated by the conditions during production. Recent studies indicate a high stability of HEV against different physicochemical conditions, whereas - among others - the virus can be efficiently inactivated by heating. Therefore, proper heating of pork meat and liver prior to consumption in general is recommended. For risk groups, avoiding shortly cured raw sausages is an additional suggestion.Further research is necessary to identify relevant risk food products, to investigate alternative transmission pathways, and to develop efficient measures in order to reduce or prevent zoonotic transmissions of the virus in future.


Assuntos
Vírus da Hepatite E , Hepatite E , Animais , Inocuidade dos Alimentos , Alemanha/epidemiologia , Hepatite E/epidemiologia , Vírus da Hepatite E/genética , Humanos , Sus scrofa , Suínos
20.
J Korean Phys Soc ; 80(8): 817-851, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35261432

RESUMO

Nonthermal biocompatible plasma (NBP) sources operating in atmospheric pressure environments and their characteristics can be used for plasma bioscience, medicine, and hygiene applications, especially for COVID-19 and citizen. This review surveyed the various NBP sources, including a plasma jet, micro-DBD (dielectric barrier discharge) and nanosecond discharged plasma. The electron temperatures and the plasma densities, which are produced using dielectric barrier discharged electrode systems, can be characterized as 0.7 ~ 1.8 eV and (3-5) × 1014-15 cm-3, respectively. Herein, we introduce a general schematic view of the plasma ultraviolet photolysis of water molecules for reactive oxygen and nitrogen species (RONS) generation inside biological cells or living tissues, which would be synergistically important with RONS diffusive propagation into cells or tissues. Of the RONS, the hydroxyl radical [OH] and hydrogen peroxide H2O2 species would mainly result in apoptotic cell death with other RONS in plasma bioscience and medicines. The diseased biological protein, cancer, and mutated cells could be treated by using a NBP or plasma activated water (PAW) resulting in their apoptosis for a new paradigm of plasma medicine.

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