BACKGROUND-Antiretroviral chemoprophylaxis before exposure is a promising approach for the prevention of human immunodeficiency virus (HIV) acquisition.
Currently,
humans are immersed in a pandemic caused by the emerging
severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),
which threatens public health worldwide. To date, no drug or vaccine
has been approved to treat the severe disease caused by this coronavirus,
COVID-19. In this paper, we will focus on the main virus-based and
host-based targets that can guide efforts in medicinal chemistry to
discover new drugs for this devastating disease. In principle, all
CoV enzymes and proteins involved in viral replication and the control
of host cellular machineries are potentially druggable targets in
the search for therapeutic options for SARS-CoV-2. This Perspective
provides an overview of the main targets from a structural point of
view, together with reported therapeutic compounds with activity against
SARS-CoV-2 and/or other CoVs. Also, the role of innate immune response
to coronavirus infection and the related therapeutic options
will be presented.
Glycogen synthase kinase 3 beta (GSK-3beta) has a central role in Alzheimer's disease (AD). Selective inhibitors which avoid tau hyperphosphorylation may represent an effective therapeutical approach to the AD pharmacotherapy and other neurodegenerative disorders. Here, we describe the synthesis, biological evaluation, and SAR of the small heterocyclic thiadiazolidinones (TDZD) as the first non-ATP competitive inhibitor of GSK-3beta. Their synthesis is based on the reactivity of sulfenyl chlorides. In GSK-3beta assays, TDZD derivatives showed IC(50) values in the micromolar range, whereas in other protein kinases assays they were devoid of any inhibitory activity. SAR studies allowed the identification of the key structural features. Finally, a possible enzymatic binding mode is proposed.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.