Latin American databases of natural products: biodiversity and drug discovery against SARS-CoV-2† † Electronic supplementary information (ESI) available. See DOI: 10.1039/d1ra01507a

In this study, we evaluated 3444 Latin American natural products using cheminformatic tools. We also characterized 196 compounds for the first time from the flora of El Salvador that were compared with the databases of secondary metabolites from Brazil, Mexico, and Panama, and 42 969 compounds (natural, semi-synthetic, synthetic) from different regions of the world. The overall analysis was performed using drug-likeness properties, molecular fingerprints of different designs, two parameters similarity, molecular scaffolds, and molecular complexity metrics. It was found that, in general, Salvadoran natural products have a large diversity based on fingerprints. Simultaneously, those belonging to Mexico and Panama present the greatest diversity of scaffolds compared to the other databases. This study provided evidence of the high structural complexity that Latin America's natural products have as a benchmark. The COVID-19 pandemic has had a negative effect on a global level. Thus, in the search for substances that may influence the coronavirus life cycle, the secondary metabolites from El Salvador and Panama were evaluated by docking against the endoribonuclease NSP-15, an enzyme involved in the SARS CoV-2 viral replication. We propose in this study three natural products as potential inhibitors of NSP-15. We performed a cheminfomatic analysis of four databases in Latin America and evaluated its potential in silico against SARS-CoV-2.

A critical overview of computational approaches employed for COVID-19 drug discovery.

COVID-19 has resulted in huge numbers of infections and deaths worldwide and brought the most severe disruptions to societies and economies since the Great Depression. Massive experimental and computational research effort to understand and characterize the disease and rapidly develop diagnostics, vaccines, and drugs has emerged in response to this devastating pandemic and more than 130 000 COVID-19-related research papers have been published in peer-reviewed journals or deposited in preprint servers. Much of the research effort has focused on the discovery of novel drug candidates or repurposing of existing drugs against COVID-19, and many such projects have been either exclusively computational or computer-aided experimental studies. Herein, we provide an expert overview of the key computational methods and their applications for the discovery of COVID-19 small-molecule therapeutics that have been reported in the research literature. We further outline that, after the first year the COVID-19 pandemic, it appears that drug repurposing has not produced rapid and global solutions. However, several known drugs have been used in the clinic to cure COVID-19 patients, and a few repurposed drugs continue to be considered in clinical trials, along with several novel clinical candidates. We posit that truly impactful computational tools must deliver actionable, experimentally testable hypotheses enabling the discovery of novel drugs and drug combinations, and that open science and rapid sharing of research results are critical to accelerate the development of novel, much needed therapeutics for COVID-19.

Latin American databases of natural products: biodiversity and drug discovery against SARS-CoV-2.

In this study, we evaluated 3444 Latin American natural products using cheminformatic tools. We also characterized 196 compounds for the first time from the flora of El Salvador that were compared with the databases of secondary metabolites from Brazil, Mexico, and Panama, and 42 969 compounds (natural, semi-synthetic, synthetic) from different regions of the world. The overall analysis was performed using drug-likeness properties, molecular fingerprints of different designs, two parameters similarity, molecular scaffolds, and molecular complexity metrics. It was found that, in general, Salvadoran natural products have a large diversity based on fingerprints. Simultaneously, those belonging to Mexico and Panama present the greatest diversity of scaffolds compared to the other databases. This study provided evidence of the high structural complexity that Latin America's natural products have as a benchmark. The COVID-19 pandemic has had a negative effect on a global level. Thus, in the search for substances that may influence the coronavirus life cycle, the secondary metabolites from El Salvador and Panama were evaluated by docking against the endoribonuclease NSP-15, an enzyme involved in the SARS CoV-2 viral replication. We propose in this study three natural products as potential inhibitors of NSP-15.

Fragment Library of Natural Products and Compound Databases for Drug Discovery.

Natural products and semi-synthetic compounds continue to be a significant source of drug candidates for a broad range of diseases, including coronavirus disease 2019 (COVID-19), which is causing the current pandemic. Besides being attractive sources of bioactive compounds for further development or optimization, natural products are excellent substrates of unique substructures for fragment-based drug discovery. To this end, fragment libraries should be incorporated into automated drug design pipelines. However, public fragment libraries based on extensive collections of natural products are still limited. Herein, we report the generation and analysis of a fragment library of natural products derived from a database with more than 400,000 compounds. We also report fragment libraries of a large food chemical database and other compound datasets of interest in drug discovery, including compound libraries relevant for COVID-19 drug discovery. The fragment libraries were characterized in terms of content and diversity.

Consensus virtual screening of dark chemical matter and food chemicals uncover potential inhibitors of SARS-CoV-2 main protease.

The pandemic caused by SARS-CoV-2 (COVID-19 disease) has claimed more than 500 000 lives worldwide, and more than nine million people are infected. Unfortunately, an effective drug or vaccine for its treatment is yet to be found. The increasing information available on critical molecular targets of SARS-CoV-2 and active compounds against related coronaviruses facilitates the proposal (or repurposing) of drug candidates for the treatment of COVID-19, with the aid of in silico methods. As part of a global effort to fight the COVID-19 pandemic, herein we report a consensus virtual screening of extensive collections of food chemicals and compounds known as dark chemical matter. The rationale is to contribute to global efforts with a description of currently underexplored chemical space regions. The consensus approach included combining similarity searching with various queries and fingerprints, molecular docking with two docking protocols, and ADMETox profiling. We propose compounds commercially available for experimental testing. The full list of virtual screening hits is disclosed.