Recent Progress toward the Discovery of Small Molecules as Novel Anti-Respiratory Syncytial Virus Agents.

Respiratory syncytial virus (RSV) stands as the foremost cause of infant hospitalization globally, ranking second only to malaria in terms of infant mortality. Although three vaccines have recently been approved for the prophylaxis of adults aged 60 and above, and pregnant women, there is currently no effective antiviral drug for treating RSV infections. The only preventive measure for infants at high risk of severe RSV disease is passive immunization through monoclonal antibodies. This Perspective offers an overview of the latest advancements in RSV drug discovery of small molecule antivirals, with particular focus on the promising findings from agents targeting the fusion and polymerase proteins. A comprehensive reflection on the current state of RSV research is also given, drawing inspiration from the lessons gleaned from HCV and HIV, while also considering the impact of the recent approval of the three vaccines.

Privileged Scaffolds for Potent and Specific Inhibitors of Mono-ADP-Ribosylating PARPs.

The identification of new targets to address unmet medical needs, better in a personalized way, is an urgent necessity. The introduction of PARP1 inhibitors into therapy, almost ten years ago, has represented a step forward this need being an innovate cancer treatment through a precision medicine approach. The PARP family consists of 17 members of which PARP1 that works by poly-ADP ribosylating the substrate is the sole enzyme so far exploited as therapeutic target. Most of the other members are mono-ADP-ribosylating (mono-ARTs) enzymes, and recent studies have deciphered their pathophysiological roles which appear to be very extensive with various potential therapeutic applications. In parallel, a handful of mono-ARTs inhibitors emerged that have been collected in a perspective on 2022. After that, additional very interesting compounds were identified highlighting the hot-topic nature of this research field and prompting an update. From the present review, where we have reported only mono-ARTs inhibitors endowed with the appropriate profile of pharmacological tools or drug candidate, four privileged scaffolds clearly stood out that constitute the basis for further drug discovery campaigns.