As part of a global effort to identify drug candidates for the treatment of COVID-19, herein, we report small molecules commercially available selected from a consensus virtual screening strategy.

Molecular acid/base properties have a significant influence on membrane permeation, metabolism, absorption, and affinity for biological targets. In particular, ionizable groups are critical in the strength of target‐molecule interactions, pharmacokinetics, and toxicity. In this study, we estimated the acid/base properties of the food chemicals from FooDB, a public compound collection with more than 22,000 compounds. It was found that the food chemicals have 40.9 % of neutral compounds, which is twice as many as that found in approved drugs. The most common functional groups among the acid groups in the food chemicals were phenols (16.1 %), phosphates (17.3 %), and carboxylates (17.3 %) while the single‐base‐containing compounds were of less interest as they accounted for just 5.5 %. To the best of our knowledge, this is the first systematic acid/base profiling of food chemicals and it is part of a continued effort to profile food chemicals for their broad interest in several areas such as nutrition and the food industry in general.

For many years drug discovery and other areas in chemistry have successfully relied on natural products. Recent advances in computational methods have made possible to study the chemical space of natural products from different sources. Ionizable acidic and basic functional groups heavily influence physicochemical properties and thus a molecule's absorption, distribution, metabolism, excretion, and toxicity characteristics as well as their affinity for biological targets. This work reports the generation and critical comparison of the acid/base profiles of ten chemical databases including seven natural products sets from different origins, a set of semisynthetic compounds, a collection of approved drugs, and a compendium of food chemicals. Similarities were found in the proportion of the main charge state categories among the natural products databases with few differences in their pKa distributions. Clear differences were observed between natural products and the approved drugs and semi‐synthetic natural products databases, whereas natural products share some trends with the food chemical database. We noted that the natural products collections comprise around 45 % of neutral compounds. The proportion of single acids was approximately twice that found for FDA drugs, and they demonstrated a similar distribution of pKa values. In contrast to drugs, only 5 % of compounds among the natural products sets had a single basic group. Likewise, simple ampholytes were less prevalent in the natural products databases relative to drugs.

The COVID-19 pandemic caused by SARS-CoV-2 has claimed more than 380,000 lives Worldwide and more than 6.5 million people are infected. Unfortunately, there is no drug or vaccine for the treatment of COVID-19. The increasing information available of key molecular targets of SARS-CoV-2 and active compounds against related coronavirus facilitates computational tools to rapidly suggest drug candidates for the treatment of COVID-19. As part of a global effort to fight the COVID-19 pandemic, herein we report a consensus virtual screening of large collections of food chemicals and compounds classified as Dark Chemical Matter. The rationale is to complement global efforts and explore regions of the chemical space currently underexplored. The consensus approach included combining similarity searching with various queries and fingerprints, molecular docking with two docking programs, and ADMETox profiling. We propose three compounds commercially available that were sent to experimental testing. We disclose the full list of virtual screening hits that can be subject to additional selection for acquisition or synthesis and experimental testing. This manuscript will be updated when the experimental testing of the selected compounds becomes available.

The acidic and basic functional groups in a molecule strongly influence its physicochemical properties, affinity for a macromolecule, pharmacokinetics, and toxicity. For instance, basicity has been correlated with molecular promiscuity, hERG blockade, and phospholipidosis. Nonetheless, no systematic characterization of the acid/base profile of epigenomic databases has been reported. This study describes an analysis of the acidic ionization constant distribution of a library of 7820 compounds with reported activity against epigenetic targets. Furthermore, the epigenomics database's acid/base profile was compared to the reference libraries of food chemicals, natural products, and approved drugs. It was found that the acid/base profile of histone lysine demethylase ligands is more similar to previously approved drugs, and histone acetyltransferase ligands have acidic and basic functional groups largely found in food chemicals and natural products; this support the potential of these libraries for finding new epigenetic inhibitors.