Human African Trypanosomiasis (HAT) is an endemic protozoan disease widespread in the sub-Saharan region that is caused by T. b. gambiense and T. b. rhodesiense. The development of molecules targeting rhodesain, the main cysteine protease of T. b. rhodesiense, has led to a panel of inhibitors endowed with micro/sub-micromolar activity towards the protozoa. However, whilst impressive binding affinity against rhodesain has been observed, the limited selectivity towards the target still remains a hard challenge for the development of antitrypanosomal agents. In this paper, we report the synthesis, biological evaluation, as well as docking studies of a series of reduced peptide bond pseudopeptide Michael acceptors (SPR10–SPR19) as potential anti-HAT agents. The new molecules show K_i values in the low-micro/sub-micromolar range against rhodesain, coupled with k_2nd values between 1314 and 6950 M⁻¹ min⁻¹. With a few exceptions, an appreciable selectivity over human cathepsin L was observed. In in vitro assays against T. b. brucei cultures, SPR16 and SPR18 exhibited single-digit micromolar activity against the protozoa, comparable to those reported for very potent rhodesain inhibitors, while no significant cytotoxicity up to 70 µM towards mammalian cells was observed. The discrepancy between rhodesain inhibition and the antitrypanosomal effect could suggest additional mechanisms of action. The biological characterization of peptide inhibitor SPR34 highlights the essential role played by the reduced bond for the antitrypanosomal effect. Overall, this series of molecules could represent the starting point for further investigations of reduced peptide bond-containing analogs as potential anti-HAT agents

Since the origin of COVID-19, everyone is getting accustomed to the new rules and regulations, travel restrictions and new lifestyle. Constant changes in the government advisories and the COVID-19 guidelines poses a real challenge for children to adapt to causing stress, anxiety and other mental health issues. Therefore, it is imperative to raise awareness about the challenges that Indian children are dealing with to help them better cope with this stressful and frantic time. The focus of this review is on various child-related problems that the Indian government is trying to tackle such as stress, depression, malnutrition, school closures, digital divide, child labor, child trafficking in context of mental health issues caused by them during COVID-19. Highlights:The reader will come to appreciate that: Digital-divide caused by shifting offline learning to online mode. Strategies implemented by Indian government to combat malnutrition Effect of COVID-19 lockdown on children suffering from mental disorders Child labor and trafficking and the strategies that aim to decrease child labor during the pandemic Educating the children appropriately regarding COVID protocols