Search

Fluoxazolevir is an aryloxazole-based entry inhibitor of hepatitis C virus (HCV). We show that fluoxazolevir inhibits fusion of HCV with hepatic cells by binding HCV envelope protein 1 to prevent fusion. Nine of ten fluoxazolevir resistance-associated substitutions are in envelope protein 1, and four are in a putative fusion peptide. Pharmacokinetic studies in mice, rats and dogs revealed that fluoxazolevir localizes to the liver. A 4-week intraperitoneal regimen of fluoxazolevir in humanized chimeric mice infected with HCV genotypes 1b, 2a or 3 resulted in a 2-log reduction in viraemia, without evidence of drug resistance. In comparison, daclatasvir, an approved HCV drug, suppressed more than 3 log of viraemia but is associated with the emergence of resistance-associated substitutions in mice. Combination therapy using fluoxazolevir and daclatasvir cleared HCV genotypes 1b and 3 in mice. Fluoxazolevir combined with glecaprevir and pibrentasvir was also effective in clearing multidrug-resistant HCV replication in mice. Fluoxazolevir may be promising as the next generation of combination drug cocktails for HCV treatment. Preclinical studies show that fluoxazolevir, which inhibits the fusion of hepatitis C virus (HCV) with hepatic cells by binding viral envelope protein 1, could be useful in drug cocktails to treat HCV.

Background COVID-19 hospitalizations and deaths disproportionately affect underserved and minority populations, emphasizing that vaccine hesitancy can be an especially important public health risk factor in these populations. Objective This study aims to characterize COVID-19 vaccine hesitancy in underserved diverse populations. Methods The Minority and Rural Coronavirus Insights Study (MRCIS) recruited a convenience sample of adults (age≥18, N=3735) from federally qualified health centers (FQHCs) in California, the Midwest (Illinois/Ohio), Florida, and Louisiana and collected baseline data in November 2020-April 2021. Vaccine hesitancy status was defined as a response of “no” or “undecided” to the question “Would you get a coronavirus vaccine if it was available?” (“yes” categorized as not hesitant). Cross-sectional descriptive analyses and logistic regression models examined vaccine hesitancy prevalence by age, gender, race/ethnicity, and geography. The expected vaccine hesitancy estimates for the general population were calculated for the study counties using published county-level data. Crude associations with demographic characteristics within each region were assessed using the chi-square test. The main effect model included age, gender, race/ethnicity, and geographical region to estimate adjusted odds ratios (ORs) and 95% CIs. Interactions between geography and each demographic characteristic were evaluated in separate models. Results The strongest vaccine hesitancy variability was by geographic region: California, 27.8% (range 25.0%-30.6%); the Midwest, 31.4% (range 27.3%-35.4%); Louisiana, 59.1% (range 56.1%-62.1%); and Florida, 67.3% (range 64.3%-70.2%). The expected estimates for the general population were lower: 9.7% (California), 15.3% (Midwest), 18.2% (Florida), and 27.0% (Louisiana). The demographic patterns also varied by geography. An inverted U-shaped age pattern was found, with the highest prevalence among ages 25-34 years in Florida (n=88, 80.0%,) and Louisiana (n=54, 79.4%; P Conclusions These findings highlight the role of local contextual factors in driving vaccine hesitancy and its demographic patterns.

ImportanceRacial and ethnic minority populations have been disproportionately affected in terms of hospitalizations and deaths during the COVID-19 pandemic. Vaccine uptake remains a barrier to full population inoculation against this highly infectious disease.ObjectiveThe purpose of this report is to describe SARS-CoV-2 vaccine interest rates in a racially, geographically, and ethnically diverse study cohort and characterize vaccine interest across a racially, ethnically, and geographically diverse study population.DesignThis report describes responses to a survey administered between November 2020 and May 2021 using a community convenience sample through a partnership between the National Minority Quality Forum (NMQF) and Federally Qualified Health Centers (FQHCs) as part of the Minority and Rural Coronavirus Insights Study (MRCIS). Analysis of survey responses from 3,624 participants are provided.ResultsEarly data from the MRCIS cohort suggest that “SARS-CoV-2 vaccine hesitancy” is more prevalent in Black versus Non-Hispanic Whites survey respondents, and the Hispanic community has positive interest in the vaccine, to a similar degree as Whites. The persistent presence of “vaccine undecideds” across different sites and racial/ethnic groups uncovers the need for more public health efforts to influence positive views about vaccination.ConclusionThese findings highlights the urgent need for interventional educational campaigns targeted at populations at risk of low vaccine interest. Focused efforts are needed to combat misinformation and explain the vaccine’s safety and effectiveness to promote its uptake and avoid low inoculation rates. Public health communication must consider differences in population groups, regions, and social determinants of health to fully address vaccine uptake disparities and overcome alleged hesitancy.Key PointsWillingness to receive the SARS CoV-2 varies among minority populations.“SARS-CoV-2 vaccine hesitancy” is more prevalent in the non-Hispanic Black population than the non-Hispanic White and Hispanic populations.Public health infrastructure is needed in underserved communities for efficient assessment and targeted communication of public health priorities such as the SARS CoV-2 vaccination.