In silicoscreening strategies for novel inhibitors of parasitic diseases

Abstract

Introduction: Parasitic diseases are a major global problem causing long-term 10 disability and death, with severe medical and psychological consequences around the world. Despite the prevalence of parasitic disease, the treatment options for many of these illnesses are still inadequate and there is a dire need for new antiparasitic drugs. In silico screening techniques, which are powerful strategies for hit generation, are widely being applied in the design 15 of new ligands for parasitic diseases. Areas covered: This article analyses the application of ligand-and structurebased virtual screening strategies against a variety of parasitic diseases and discusses the benefits of the integration between computational and experimental approaches toward the discovery of new antiparasitic agents. The 20 analysis is illustrated by recent examples, with emphasis on the strategies reported within the past 2 years. Expert opinion: Virtual screening techniques are powerful tools commonly used in drug discovery against parasitic diseases, which have provided new opportunities for the identification of several novel compound classes with 25 antiparasitic activity.

Structure- and ligand-based drug design approaches for neglected tropical diseases

“…Several steps of the drug discovery process (e.g., hit identification, lead optimization, NCE discovery) can be improved in a rational way with the application of SBDD and LBDD methods [2,[7][8][9]. In this context, virtual screening has become a highly valued and widely used tool for the identification of hits and lead compounds for a variety of therapeutically important target proteins [2,[49][50][51][52].…”

“…In this context, virtual screening has become a highly valued and widely used tool for the identification of hits and lead compounds for a variety of therapeutically important target proteins [2,[49][50][51][52]. An example can be seen in the medicinal chemistry approach employed for the discovery of new inhibitors of Schistosoma mansoni purine nucleoside phosphorylase (SmPNP), which outlines a successful scenario for the integration of computational and experimental methods.…”

“…Neglected tropical diseases (NTDs) place a heavy burden on society in terms of long-term disability, illness, and death, with severe social and economic consequences for millions of people worldwide [1][2][3]. Despite their high prevalence, in most cases the treatment for NTDs is inadequate and incredibly limited (it is usually characterized by a low efficacy and considerable toxicity of the existing drugs), leading to an urgent and immediate demand for new drugs.…”

“…It is worth noting that these knowledge-driven approaches can be explored in combination, creating new opportunities for innovation in medicinal chemistry in order to maximize the accomplishment of drug discovery projects. Recent successful examples highlight the diversity of SBDD and LBDD strategies, assembling the most powerful concepts in chemistry and biology, with particular emphasis on the field of NTDs [2,[7][8][9]. This paper outlines the fundamental principles and state of the art in the integration of SBDD and LBDD strategies for the discovery of innovative chemotherapy agents for a variety of NTDs, highlighting advances, limitations, and future perspectives in medicinal chemistry.…”

Structure-Based Drug Design to Overcome Drug Resistance: Challenges and Opportunities

“…The use of SBDD approaches has a long and rich history in drug discovery [8][9][10][11][12][13]. Structural information about the molecular target can aid either the discovery of new inhibitors through virtual screening [14][15][16], or the optimization of known ligands [11,17].…”