Antiviral Activity of Quercetin Hydrate against Zika Virus Saivish, Marielena Vogel; Menezes, Gabriela de Lima; da Silva, Roosevelt Alves ...
International journal of molecular sciences,
04/2023, Letnik:
24, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Zika virus (ZIKV) has re-emerged in recent decades, leading to outbreaks of Zika fever in Africa, Asia, and Central and South America. Despite its drastic re-emergence and clinical impact, no ...vaccines or antiviral compounds are available to prevent or control ZIKV infection. This study evaluated the potential antiviral activity of quercetin hydrate against ZIKV infection and demonstrated that this substance inhibits virus particle production in A549 and Vero cells under different treatment conditions. In vitro antiviral activity was long-lasting (still observed 72 h post-infection), suggesting that quercetin hydrate affects multiple rounds of ZIKV replication. Molecular docking indicates that quercetin hydrate can efficiently interact with the specific allosteric binding site cavity of the NS2B-NS3 proteases and NS1-dimer. These results identify quercetin as a potential compound to combat ZIKV infection in vitro.
Ilhéus virus (ILHV) is a neglected mosquito-borne flavivirus. ILHV infection may lead to Ilhéus fever, an emerging febrile disease like dengue fever with the potential to evolve into a severe ...neurological disease characterized by meningoencephalitis; no specific treatments are available for this disease. This study assessed the antiviral properties of caffeic acid, an abundant component of plant-based food products that is also compatible with the socioeconomic limitations associated with this neglected infectious disease. The in vitro activity of caffeic acid on ILHV replication was investigated in Vero and A549 cell lines using plaque assays, quantitative RT-PCR, and immunofluorescence assays. We observed that 500 µM caffeic acid was virucidal against ILHV. Molecular docking indicated that caffeic acid might interact with an allosteric binding site on the envelope protein.
The purpose of this study was to evaluate patients' and orthodontists' perspectives on knowledge of techniques for reducing orthodontic treatment time and acceptance of these techniques.
A total of ...200 individuals were interviewed and equally divided into two groups: orthodontist group (62 female and 38 male; mean age, 38.07 years) and patient group (52 female and 48 male; mean age, 22.61 years; in the active stage of fixed orthodontic treatment). One questionnaire for each group was administered, including questions about the duration of orthodontic treatment and techniques used for treatment optimization, such as corticotomy, distraction osteogenesis, vibration, and laser therapy. The associations between variables were analyzed by the χ2 test at a significance level of 5%.
Among orthodontists, 76% knew at least one technique to reduce the treatment duration, with corticotomy being the most frequently cited (66%); however, only 12% used one or more of these techniques. Laser therapy was the most frequently implemented technique (7%). Regarding the duration of orthodontic treatment, the mean time reported by orthodontists was 19 to 24 months, regardless of the technique or the experience of the orthodontist. Furthermore, 39% of patients expected their treatment to last for more than 24 months, with 50% accepting to undergo further procedures to reduce this duration.
Patients are willing to undergo additional procedures to reduce the treatment duration and to bear additional costs. However, despite their knowledge, orthodontists do not apply or offer these techniques to the patients.
The emergence of the Brazilian variant of concern, Gamma lineage (P.1), impacted the epidemiological profile of COVID-19 cases due to its higher transmissibility rate and immune evasion ability.
We ...sequenced 305 SARS-CoV-2 whole-genomes and performed phylogenetic analyses to identify introduction events and the circulating lineages. Additionally, we use epidemiological data of COVID-19 cases, severe cases, and deaths to measure the impact of vaccination coverage and mortality risk.
Here we show that Gamma introduction in São José do Rio Preto, São Paulo, Brazil, was followed by the displacement of seven circulating SARS-CoV-2 variants and a rapid increase in prevalence two months after its first detection in January 2021. Moreover, Gamma variant is associated with increased mortality risk and severity of COVID-19 cases in younger age groups, which corresponds to the unvaccinated population at the time.
Our findings highlight the beneficial effects of vaccination indicated by a pronounced reduction of severe cases and deaths in immunized individuals, reinforcing the need for rapid and massive vaccination.
Repurposed drugs for treatment of new onset disease may be an effective therapeutic shortcut. We aimed to evaluate the efficacy of repurposed antivirals compared to placebo in lowering SARS-CoV2 ...viral load of COVID-19 patients.
REVOLUTIOn is a randomised, parallel, blinded, multistage, superiority and placebo controlled randomised trial conducted in 35 centres in Brazil. We include patients aged 18 years or older admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, symptoms onset 9 days or less and SpO2 94% or lower at room air were eligible. All participants were randomly allocated to receive either atazanavir, daclatasvir or sofosbuvir/daclatasvir or placebo for 10 days. The primary outcome was the decay rate (slope) of the SARS-CoV-2 viral load logarithm assessed in the modified intention to-treat population. This trial was registered with ClinicalTrials.gov, number NCT04468087.
Between February 09, 2021, and August 04, 2021, 255 participants were enrolled and randomly assigned to atazanavir (n = 64), daclatasvir (n = 66), sofosbuvir/daclatasvir (n = 67) or placebo (n = 58). Compared to placebo group, the change from baseline to day 10 in log viral load was not significantly different for any of the treatment groups (0.05 95% CI, −0.03 to 0.12, −0.02 95% CI, −0.09 to 0.06, and −0.03 95% CI, −0.11 to 0.04 for atazanavir, daclatasvir and sofosbuvir/daclatasvir groups respectively). There was no significant difference in the occurrence of serious adverse events between treatment groups.
No significant reduction in viral load was observed from the use of atazanavir, daclatasvir or sofosbuvir/daclatasvir compared to placebo in hospitalised COVID-19 patients who need oxygen support with symptoms onset 9 days or less.
Ministério da Ciência, Tecnologia e Inovação (MCTI) - Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ); Cia Latino-Americana de Medicamentos (Clamed); Cia Industrial H. Carlos Schneider (Ciser); Hospital Research Foundation Incorporation, Australia, HCor São Paulo; Blanver Farmoquímica; Instituto de Tecnologia em Fármacos (Farmanguinhos) da Fundação Oswaldo Cruz (Fiocruz); Coordenação Geral de Planejamento Estratégico (Cogeplan)/Fiocruz; and Fundação de apoio a Fiocruz (Fiotec, VPGDI-054-FIO-20-2-13).
Background: Repurposed drugs for treatment of new onset disease may be an effective therapeutic shortcut. We aimed to evaluate the efficacy of repurposed antivirals compared to placebo in lowering ...SARS-CoV2 viral load of COVID-19 patients. Methods: REVOLUTIOn is a randomised, parallel, blinded, multistage, superiority and placebo controlled randomised trial conducted in 35 centres in Brazil. We include patients aged 18 years or older admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, symptoms onset 9 days or less and SpO2 94% or lower at room air were eligible. All participants were randomly allocated to receive either atazanavir, daclatasvir or sofosbuvir/daclatasvir or placebo for 10 days. The primary outcome was the decay rate (slope) of the SARS-CoV-2 viral load logarithm assessed in the modified intention to-treat population. This trial was registered with ClinicalTrials.gov, number NCT04468087. Findings: Between February 09, 2021, and August 04, 2021, 255 participants were enrolled and randomly assigned to atazanavir (n = 64), daclatasvir (n = 66), sofosbuvir/daclatasvir (n = 67) or placebo (n = 58). Compared to placebo group, the change from baseline to day 10 in log viral load was not significantly different for any of the treatment groups (0.05 95% CI, −0.03 to 0.12, −0.02 95% CI, −0.09 to 0.06, and −0.03 95% CI, −0.11 to 0.04 for atazanavir, daclatasvir and sofosbuvir/daclatasvir groups respectively). There was no significant difference in the occurrence of serious adverse events between treatment groups. Interpretation: No significant reduction in viral load was observed from the use of atazanavir, daclatasvir or sofosbuvir/daclatasvir compared to placebo in hospitalised COVID-19 patients who need oxygen support with symptoms onset 9 days or less. Funding: Ministério da Ciência, Tecnologia e Inovação (MCTI) - Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ); Cia Latino-Americana de Medicamentos (Clamed); Cia Industrial H. Carlos Schneider (Ciser); Hospital Research Foundation Incorporation, Australia, HCor São Paulo; Blanver Farmoquímica; Instituto de Tecnologia em Fármacos (Farmanguinhos) da Fundação Oswaldo Cruz (Fiocruz); Coordenação Geral de Planejamento Estratégico (Cogeplan)/Fiocruz; and Fundação de apoio a Fiocruz (Fiotec, VPGDI-054-FIO-20-2-13).
Repurposed drugs are important in resource-limited settings because the interventions are more rapidly available, have already been tested safely in other populations and are inexpensive. Repurposed ...drugs are an effective solution, especially for emerging diseases such as COVID-19. The REVOLUTIOn trial has the objective of evaluating three repurposed antiviral drugs, atazanavir, daclatasvir and sofosbuvir, already used for HIV- and hepatitis C virus-infected patients in a randomized, placebo-controlled, adaptive, multiarm, multistage study. The drugs will be tested simultaneously in a Phase II trial to first identify whether any of these drugs alone or in combination reduce the viral load. If they do, a Phase III trial will be initiated to investigate if these medications are capable of increasing the number of days free respiratory support. Participants must be hospitalized adults aged ≥ 18 years with initiation of symptoms ≤ 9 days and SpO2 ≤ 94% in room air or a need for supplemental oxygen to maintain an SpO2 > 94%. The expected total sample size ranges from 252 to 1,005 participants, depending on the number of stages that will be completed in the study. Hence, the protocol is described here in detail together with the statistical analysis plan. In conclusion, the REVOLUTIOn trial is designed to provide evidence on whether atazanavir, daclatasvir or sofosbuvir decrease the SARS-CoV-2 load in patients with COVID-19 and increase the number of days patients are free of respiratory support. In this protocol paper, we describe the rationale, design, and status of the trial. ClinicalTrials.gov identifier: NCT04468087.
A análise da notificação de casos de AIDS no Brasil entre os anos de 2020 e 2023 revelou nuances complexas na distribuição dos casos por faixa etária e região do país. Utilizando dados fornecidos ...pelo Ministério da Saúde, por intermédio do Departamento de HIV/AIDS, Tuberculose, Hepatites Virais e Infecções Sexualmente Transmissíveis (Dathi), conduzimos uma investigação minuciosa da incidência da doença e suas tendências ao longo deste período. Os resultados obtidos oferecem uma visão abrangente da epidemiologia da AIDS no contexto brasileiro. Observou-se uma disparidade marcante entre as regiões, com o Sudeste liderando em termos absolutos de casos notificados, seguido pelo Nordeste, Sul, Centro-Oeste e Norte. Essa discrepância regional pode ser atribuída a uma série de fatores, incluindo densidade populacional, acesso a serviços de saúde e diferenças socioeconômicas entre as regiões. Ao desmembrar a distribuição dos casos por faixa etária, destacou-se a predominância da faixa de 40-49 anos como a mais afetada em todas as regiões. Essa constatação sugere uma possível associação entre a idade e a exposição ao vírus, bem como a prevalência de comportamentos de risco nessa faixa etária. No entanto, é importante ressaltar que as faixas etárias mais jovens e mais velhas também apresentaram números significativos de casos notificados, destacando a necessidade de estratégias de prevenção e educação abrangentes que atendam a todas as faixas etárias. Essas descobertas fornecem insights valiosos para a formulação e implementação de políticas públicas direcionadas ao enfrentamento da epidemia de AIDS no Brasil. O entendimento das disparidades regionais e dos padrões de distribuição por faixa etária é essencial para direcionar recursos e intervenções de forma eficaz, visando reduzir a incidência da doença e melhorar o acesso a serviços de saúde para todas as populações afetadas.
