The COVID-19 pandemic in Australia: Public health responses, opportunities and challenges.

In responding to the COVID-19 pandemic, each country is presented with both opportunities and challenges, some unique and some shared with the global community. It is important to not only recognize, but to embrace them as drivers of the public to the current pandemic success. In this commentary, we discuss the opportunities and challenges that may affect ongoing public health programming in Australia within the current context of epidemiology. COVID-19 within Australia has to date been effectively suppressed through the implementation of nationally coordinated, in which the state delivered public policy, guidelines and practice, and successful establishment of a comprehensive testing, contact tracing, patient isolation and contact quarantine regime combined with national and state social distancing, hygiene etiquette and movement restrictions. However, despite its success to date great challenges lay ahead for future public health policy with the threat of a second wave, or more likely, multiple smaller outbreaks across various population centres. Therefore, policies that aim to balance the twin socioeconomic and health impacts are crucial. The experience of Australia in managing its COVID-19 response can provide a case study for other countries to reshape or adapt their policies and actions in the context of emerging global health crises.

Synthesis and In Vitro Antiproliferative Activity of 11-Substituted Neocryptolepines with a Branched ω-Aminoalkylamino Chain.

Neocryptolepine, which is a kind of tetracyclic indoloquinoline alkaloid, exhibits the inhibition of topoisomerase II and shows antiproliferative activity. The present study describes the synthesis and antiproliferative evaluation of several neocryptolepine analogues carrying a branched, functionalized dibasic side chain at C11. These 2-substituted 5-methyl-indolo[2,3-b]quinoline derivatives were prepared by nucleophilic aromatic substitution (SNAr) of 11-chloroneocryptolepines with appropriate 1,2- and 1,3-diamines. Some of the 11-(ω-aminoalkylamino) derivatives were further transformed into 11-ureido and thioureido analogues. Many of the prepared neocryptolepine derivatives showed submicromolar antiproliferative activity against the human leukemia MV4-11 cell line. Among them, 11-(3-amino-2-hydroxy)propylamino derivatives 2h and 2k were the most cytotoxic with a mean IC50 value of 0.042 µM and 0.057 µM against the MV4-11 cell line, 0.197 µM and 0.1988 µM against the A549 cell line, and 0.138 µM and 0.117 µM against the BALB/3T3 cell line, respectively.

Synthesis and in vitro cytotoxic effect of 6-amino-substituted 11H- and 11Me-indolo[3,2-c]quinolines.

A series of 6-amino-11H- indolo[3,2-c]quinoline derivatives with various substituents on the quinoline ring were synthesized. A methyl group introduced to N-11 of the intermediate 4 to elaborate novel analog 7. The cytotoxic effect of these 6-amino-substituted 11H- and 11-methyl-indolo[3,2-c]quinoline derivatives in vitro were tested against MV4-11 (human leukemia), A549 (non-small cell lung cancer) and HCT116 (colon cancer) and BALB/3T3 (normal murine fibroblasts). All the N-11 methylated compounds significantly increased the cytotoxicity. Compound 7p was most active with the IC50 value of 0.052 µM against the MV4-11 cell line, and also exhibited a selective activity against A549, HCT116 and BALB/3T3 cell line, with the respective IC50 values of 0.112, 0.007 and 0.083 µM, which were higher or comparable to those of the anticancer drug doxorubicin HCl. The binding constants of 5g and 7h to salmon fish sperm DNA were also evaluated using UV-vis absorption spectroscopy, indicating intercalation binding with constants of 1.05 × 10(6) L/mol and 4.84 × 10(6) L/mol.

Patient-based transcriptome-wide analysis identify interferon and ubiquination pathways as potential predictors of influenza A disease severity.

BACKGROUND: The influenza A virus is an RNA virus that is responsible for seasonal epidemics worldwide with up to five million cases of severe illness and 500,000 deaths annually according to the World Health Organization estimates. The factors associated with severe diseases are not well defined, but more severe disease is more often seen among persons aged >65 years, infants, pregnant women, and individuals of any age with underlying health conditions. METHODOLOGY/PRINCIPAL FINDINGS: Using gene expression microarrays, the transcriptomic profiles of influenza-infected patients with severe (N = 11), moderate (N = 40) and mild (N = 83) symptoms were compared with the febrile patients of unknown etiology (N = 73). We found that influenza-infected patients, regardless of their clinical outcomes, had a stronger induction of antiviral and cytokine responses and a stronger attenuation of NK and T cell responses in comparison with those with unknown etiology. More importantly, we found that both interferon and ubiquitination signaling were strongly attenuated in patients with the most severe outcomes in comparison with those with moderate and mild outcomes, suggesting the protective roles of these pathways in disease pathogenesis. CONCLUSION/SIGNIFICANCES: The attenuation of interferon and ubiquitination pathways may associate with the clinical outcomes of influenza patients.