Direct-Acting Antivirals and Host-Targeting Approaches against Enterovirus B Infections: Recent Advances.

Enterovirus B (EV-B)-related diseases, which can be life threatening in high-risk populations, have been recognized as a serious health problem, but their clinical treatment is largely supportive, and no selective antivirals are available on the market. As their clinical relevance has become more serious, efforts in the field of anti-EV-B inhibitors have greatly increased and many potential antivirals with very high selectivity indexes and promising in vitro activities have been discovered. The scope of this review encompasses recent advances in the discovery of new compounds with anti-viral activity against EV-B, as well as further progress in repurposing drugs to treat these infections. Current progress and future perspectives in drug discovery against EV-Bs are briefly discussed and existing gaps are spotlighted.

Malaria transmission blocking compounds: a patent review.

INTRODUCTION: Despite substantial progress in the field, malaria remains a global health issue and currently available control strategies are not sufficient to achieve eradication. Agents able to prevent transmission are likely to have a strong impact on malaria control and have been prioritized as a primary objective to reduce the number of secondary infections. Therefore, there is an increased interest in finding novel drugs targeting sexual stages of Plasmodium and innovative methods to target malaria transmission from host to vector, and vice versa. AREAS COVERED: This review covers innovative transmission-blocking inventions patented between 2015 and October 2021. The focus is on chemical interventions, which could be used as 'chemical vaccines' to prevent transmission (small molecules, carbohydrates, and polypeptides). EXPERT OPINION: Even though the development of novel strategies to block transmission still requires fundamental additional research and a deeper understanding of parasite sexual stages biology, the research in this field has significantly accelerated. Among innovative inventions patented over the last 6 years, the surface-delivery of antimalarial drugs to kill transmission-stages parasites in mosquitoes holds the highest promise for success in malaria control strategies, opening completely new scenarios in malaria transmission-blocking drug discovery.

A Novel Class of Dual-Acting DCH-CORMs Counteracts Oxidative Stress-Induced Inflammation in Human Primary Tenocytes.

Carbon monoxide (CO) can prevent cell and tissue damage by restoring redox homeostasis and counteracting inflammation. CO-releasing molecules (CORMs) can release a controlled amount of CO to cells and are emerging as a safer therapeutic alternative to delivery of CO in vivo. Sustained oxidative stress and inflammation can cause chronic pain and disability in tendon-related diseases, whose therapeutic management is still a challenge. In this light, we developed three small subsets of 1,5-diarylpyrrole and pyrazole dicobalt(0)hexacarbonyl (DCH)-CORMs to assess their potential use in musculoskeletal diseases. A myoglobin-based spectrophotometric assay showed that these CORMs act as slow and efficient CO-releasers. Five selected compounds were then tested on human primary-derived tenocytes before and after hydrogen peroxide stimulation to assess their efficacy in restoring cell redox homeostasis and counteracting inflammation in terms of PGE2 secretion. The obtained results showed an improvement in tendon homeostasis and a cytoprotective effect, reflecting their activity as CO-releasers, and a reduction of PGE2 secretion. As these compounds contain structural fragments of COX-2 selective inhibitors, we hypothesized that such a composite mechanism of action results from the combination of CO-release and COX-2 inhibition and that these compounds might have a potential role as dual-acting therapeutic agents in tendon-derived diseases.

SAR Analysis of Small Molecules Interfering with Energy-Metabolism in Mycobacterium tuberculosis.

Tuberculosis remains the world's top infectious killer: it caused a total of 1.5 million deaths and 10 million people fell ill with TB in 2018. Thanks to TB diagnosis and treatment, mortality has been falling in recent years, with an estimated 58 million saved lives between 2000 and 2018. However, the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mtb strains is a major concern that might reverse this progress. Therefore, the development of new drugs acting upon novel mechanisms of action is a high priority in the global health agenda. With the approval of bedaquiline, which targets mycobacterial energy production, and delamanid, which targets cell wall synthesis and energy production, the energy-metabolism in Mtb has received much attention in the last decade as a potential target to investigate and develop new antimycobacterial drugs. In this review, we describe potent anti-mycobacterial agents targeting the energy-metabolism at different steps with a special focus on structure-activity relationship (SAR) studies of the most advanced compound classes.