Naringenin is a flavonoid belonging to flavanones subclass. It is widely distributed in several Citrus fruits, bergamot, tomatoes and other fruits, being also found in its glycosides form (mainly naringin). Several biological activities have been ascribed to this phytochemical, among them antioxidant, antitumor, antiviral, antibacterial, anti-inflammatory, antiadipogenic and cardioprotective effects. Nonetheless, most of the data reported have been obtained from in vitro or in vivo studies. Although some clinical studies have also been performed, the main focus is on naringenin bioavailability and cardioprotective action. In addition, these studies were done in compromised patients (i.e., hypercholesterolemic and overweight), with a dosage ranging between 600 and 800 μM/day, whereas the effect on healthy volunteers is still debatable. In fact, naringenin ability to improve endothelial function has been well-established. Indeed, the currently available data are very promising, but further research on pharmacokinetic and pharmacodynamic aspects is encouraged to improve both available production and delivery methods and to achieve feasible naringenin-based clinical formulations.

The Therapeutic Potential of Naringenin: A Review of Clinical Trials.

Pan-Assay Interference Compounds (PAINS) are very familiar to medicinal chemists who have spent time fruitlessly trying to optimize these nonprogressible compounds. Electronic filters formulated to recognize PAINS can process hundreds and thousands of compounds in seconds and are in widespread current use to identify PAINS in order to exclude them from further analysis. However, this practice is fraught with danger because such black box treatment is simplistic. Here, we outline for the first time all necessary considerations for the appropriate use of PAINS filters.

Seven Year Itch: Pan-Assay Interference Compounds (PAINS) in 2017-Utility and Limitations.

Activation of Nrf2 signaling by natural products-can it alleviate diabetes?

Virtual screening consists of using computational tools to predict potentially bioactive compounds from files containing large libraries of small molecules. Virtual screening is becoming increasingly popular in the field of drug discovery as in silico techniques are continuously being developed, improved, and made available. As most of these techniques are easy to use, both private and public organizations apply virtual screening methodologies to save resources in the laboratory. However, it is often the case that the techniques implemented in virtual screening workflows are restricted to those that the research team knows. Moreover, although the software is often easy to use, each methodology has a series of drawbacks that should be avoided so that false results or artifacts are not produced. Here, we review the most common methodologies used in virtual screening workflows in order to both introduce the inexperienced researcher to new methodologies and advise the experienced researcher on how to prevent common mistakes and the improper usage of virtual screening methodologies.

https://www.mdpi.com/1422-0067/20/6/1375/pdf

The Light and Dark Sides of Virtual Screening: What Is There to Know?

Human infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause coronavirus disease 19 (COVID-19) and there is currently no cure. The 3C-like protease (3CLpro), a highly conserved protease indispensable for replication of coronaviruses, is a promising target for development of broad-spectrum antiviral drugs. To advance the speed of drug discovery and development, we investigated the inhibition of SARS-CoV-2 3CLpro by natural products derived from Chinese traditional medicines. Baicalin and baicalein were identified as the first non-covalent, non-peptidomimetic inhibitors of SARS-CoV-2 3CLpro and exhibited potent antiviral activities in a cell-based system. Remarkably, the binding mode of baicalein with SARS-CoV-2 3CLpro determined by X-ray protein crystallography is distinctly different from those of known inhibitors. Baicalein is perfectly ensconced in the core of the substrate-binding pocket by interacting with two catalytic residues, the crucial S1/S2 subsites and the oxyanion loop, acting as a “shield” in front of the catalytic dyad to prevent the peptide substrate approaching the active site. The simple chemical structure, unique mode of action, and potent antiviral activities in vitro, coupled with the favorable safety data from clinical trials, emphasize that baicalein provides a great opportunity for the development of critically needed anti-coronaviral drugs.

/pdf/discovery-of-baicalin-and-baicalein-as-novel-natural-product-1ct3uodmd2.pdf

Discovery of baicalin and baicalein as novel, natural product inhibitors of SARS-CoV-2 3CL protease in vitro

Author(s): Aldrich, Courtney; Bertozzi, Carolyn; Georg, Gunda I; Kiessling, Laura; Lindsley, Craig; Liotta, Dennis; Merz, Kenneth M; Schepartz, Alanna; Wang, Shaomeng

https://pubs.acs.org/doi/pdf/10.1021/acschembio.7b00119

The Ecstasy and Agony of Assay Interference Compounds

https://pubs.acs.org/doi/pdf/10.1021/acscentsci.7b00069

The Ecstasy and Agony of Assay Interference Compounds.

https://pubs.acs.org/doi/pdf/10.1021/acsmedchemlett.7b00056

https://pubs.acs.org/doi/pdf/10.1021/acschemneuro.7b00064

/pdf/the-ecstasy-and-agony-of-assay-interference-compounds-4bvmamz8pr.pdf

Kenneth M. Merz

Papers

The Ecstasy and Agony of Assay Interference Compounds

The Ecstasy and Agony of Assay Interference Compounds.

The Ecstasy and Agony of Assay Interference Compounds.

The Ecstasy and Agony of Assay Interference Compounds.

The Ecstasy and Agony of Assay Interference Compounds.