The host-targeting compound peruvoside has a broad-spectrum antiviral activity against positive-sense RNA viruses

Positive-sense RNA viruses modify intracellular calcium stores, endoplasmic reticulum and Golgi apparatus (Golgi) to generate membranous replication organelles known as viral factories. Viral factories provide a conducive and substantial enclave for essential virus replication via concentrating necessary cellular factors and viral proteins in proximity. Here, we identified the vital role of a broad-spectrum antiviral, peruvoside in limiting the formation of viral factories. Mechanistically, we revealed the pleiotropic cellular effect of Src and PLC kinase signaling via cyclin-dependent kinase 1 signaling leads to Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1 (GBF1) phosphorylation and Golgi vesiculation by peruvoside treatment. The ramification of GBF1 phosphorylation fosters GBF1 deprivation consequentially activating downstream antiviral signaling by dampening viral factories formation. Further investigation showed signaling of ERK1/2 pathway via cyclin-dependent kinase 1 activation leading to GBF1 phosphorylation at Threonine 1337 (T1337). We also showed 100% of protection in peruvoside-treated mouse model with a significant reduction in viral titre and without measurable cytotoxicity in serum. These findings highlight the importance of dissecting the broad-spectrum antiviral therapeutics mechanism and pave the way for consideration of peruvoside, host-directed antivirals for positive-sense RNA virus-mediated disease, in the interim where no vaccine is available.

Calcitriol, the active form of vitamin D, is a promising candidate for COVID-19 prophylaxis

COVID-19, the disease caused by SARS-CoV-2 (1), was declared a pandemic by the World Health Organization (WHO) in March 2020 (2). While awaiting a vaccine, several antivirals are being used to manage the disease with limited success (3, 4). To expand this arsenal, we screened 4 compound libraries: a United States Food and Drug Administration (FDA) approved drug library, an angiotensin converting enzyme-2 (ACE2) targeted compound library, a flavonoid compound library as well as a natural product library. Of the 121 compounds identified with activity against SARS-CoV-2, 7 were shortlisted for validation. We show for the first time that the active form of Vitamin D, calcitriol, exhibits significant potent activity against SARS-CoV-2. This finding paves the way for consideration of host-directed therapies for ring prophylaxis of contacts of SARS-CoV-2 patients.

Bacteriocin-capped silver nanoparticles for enhanced antimicrobial efficacy against food pathogens.

Bacteriocins produced by lactic acid bacteria are safer alternatives to the more popularly used chemical preservatives which exhibit several adverse effects. The bacteriocins have an advantage of being efficient in controlling food pathogens without possessing any side-effects. However, the bacteriocins have a limitation of exhibiting a narrow antimicrobial spectrum and having a high-dosage requirement. With an aim to combat these limitations, the present study involved the biosynthesis of bacteriocin-capped nanoparticles, using two bacteriocins (Bac4463 and Bac22) extracted and purified from Lactobacillus strains. Nanoconjugates synthesised at optimum conditions were characterized using various physico-chemical techniques. The interaction of bacteriocin-capped silver nanoparticles with the pathogenic bacteria was observed using scanning electron microscopy, wherein the deformed and elongated cells were clearly visible. In vitro antimicrobial efficacy of both Bac4463-capped silver nanoparticles and Bac22-capped silver nanoparticles against different food pathogens was observed to be enhanced in comparison to the antimicrobial activity of bacteriocins alone. Minimum inhibitory concentration was observed to be as low as 8 µg/ml for Bac4463-capped silver nanoparticles against Staphylococcus aureus, and 2 µg/ml for Bac22-capped silver nanoparticles against Shigella flexneri. This study, therefore, recommends the use of bacteriocin-capped nanoparticles as food preservatives to control the growth of food spoiling bacteria.

Managing urinary tract infections through phage therapy: a novel approach.

Upsurge in the instances of antibiotic-resistant uropathogenic Escherichia .coli (UPECs) strains has repositioned the attention of researchers towards a century old antimicrobial approach popularly known as phage therapy. Rise of extended spectrum beta lactamase (ESBL) and biofilm producing strains has added another step of hurdle in treatment of uropathogens with conventional antibiotics, thus providing a further impetus for search for exploring new therapeutic measures. In this direction, bacteriophages, commonly called phages, are recently being considered as potential alternatives for treatment of UPECs. Phages are the tiniest form of viruses which are ubiquitous in nature and highly specific for their host. This review discusses the possible ways of using natural phages, genetically engineered phages, and phage lytic enzymes (PLEs) as an alternative antimicrobial treatment for urinary tract infections. The review also sheds light on the synergistic use of conventional antibiotics with phages or PLEs for treatment of uropathogens. These methods of using phages and their derivatives, alone or in combination with antibiotics, have proved fruitful so far in in vitro studies. However, in vivo studies are required to make them accessible for human use. The present review is a concerted effort towards putting together all the information available on the subject.

Health and human rights in eastern Myanmar after the political transition: a population-based assessment using multistaged household cluster sampling.

BACKGROUND: Myanmar transitioned to a nominally civilian parliamentary government in March 2011. Qualitative reports suggest that exposure to violence and displacement has declined while international assistance for health services has increased. An assessment of the impact of these changes on the health and human rights situation has not been published. METHODS AND FINDINGS: Five community-based organizations conducted household surveys using two-stage cluster sampling in five states in eastern Myanmar from July 2013-September 2013. Data was collected from 6, 178 households on demographics, mortality, health outcomes, water and sanitation, food security and nutrition, malaria, and human rights violations (HRV). Among children aged 6-59 months screened, the prevalence of global acute malnutrition (representing moderate or severe malnutrition) was 11.3% (8.0-14.7). A total of 250 deaths occurred during the year prior to the survey. Infant deaths accounted for 64 of these (IMR 94.2; 95% CI 66.5-133.5) and there were 94 child deaths (U5MR 141.9; 95% CI 94.8-189.0). 10.7% of households (95% CI 7.0-14.5) experienced at least one HRV in the past year, while four percent reported 2 or more HRVs. Household exposure to one or more HRVs was associated with moderate-severe malnutrition among children (14.9 vs. 6.8%; prevalence ratio 2.2, 95% CI 1.2-4.2). Household exposure to HRVs was associated with self-reported fair or poor health status among respondents (PR 1.3; 95% CI 1.1-1.5). CONCLUSION: This large survey of health and human rights demonstrates that two years after political transition, vulnerable populations of eastern Myanmar are less likely to experience human rights violations compared to previous surveys. However, access to health services remains constrained, and risk of disease and death remains higher than the country as a whole. Efforts to address these poor health indicators should prioritize support for populations that remain outside the scope of most formal government and donor programs.

Need for a gender-sensitive human security framework: results of a quantitative study of human security and sexual violence in Djohong District, Cameroon.

BACKGROUND: Human security shifts traditional concepts of security from interstate conflict and the absence of war to the security of the individual. Broad definitions of human security include livelihoods and food security, health, psychosocial well-being, enjoyment of civil and political rights and freedom from oppression, and personal safety, in addition to absence of conflict. METHODS: In March 2010, we undertook a population-based health and livelihood study of female refugees from conflict-affected Central African Republic living in Djohong District, Cameroon and their female counterparts within the Cameroonian host community. Embedded within the survey instrument were indicators of human security derived from the Leaning-Arie model that defined three domains of psychosocial stability suggesting individuals and communities are most stable when their core attachments to home, community and the future are intact. RESULTS: While the female refugee human security outcomes describe a population successfully assimilated and thriving in their new environments based on these three domains, the ability of human security indicators to predict the presence or absence of lifetime and six-month sexual violence was inadequate. Using receiver operating characteristic (ROC) analysis, the study demonstrates that common human security indicators do not uncover either lifetime or recent prevalence of sexual violence. CONCLUSIONS: These data suggest that current gender-blind approaches of describing human security are missing serious threats to the safety of one half of the population and that efforts to develop robust human security indicators should include those that specifically measure violence against women.