Harnessing Brazilian biodiversity database: identification of flavonoids as potential inhibitors of SARS-CoV-2 main protease using computational approaches and all-atom molecular dynamics simulation.

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is the etiological agent responsible for the global outbreak of COVID-19 (Coronavirus Disease 2019). The main protease of SARS-CoV-2, Mpro, is a key enzyme that plays a vital role in mediating viral replication and transcription. In this study, a comprehensive computational approach was employed to investigate the binding affinity, selectivity, and stability of natural product candidates as potential new antivirals acting on the viral polyprotein processing mediated by SARS-CoV-2 Mpro.

Applications of Virtual Screening in Bioprospecting: Facts, Shifts, and Perspectives to Explore the Chemo-Structural Diversity of Natural Products.

Natural products are continually explored in the development of new bioactive compounds with industrial applications, attracting the attention of scientific research efforts due to their pharmacophore-like structures, pharmacokinetic properties, and unique chemical space. The systematic search for natural sources to obtain valuable molecules to develop products with commercial value and industrial purposes remains the most challenging task in bioprospecting. Virtual screening strategies have innovated the discovery of novel bioactive molecules assessing large compound libraries, favoring the analysis of their chemical space, pharmacodynamics, and their pharmacokinetic properties, thus leading to the reduction of financial efforts, infrastructure, and time involved in the process of discovering new chemical entities.

Predicting cell-penetrating peptides using machine learning algorithms and navigating in their chemical space.

Cell-penetrating peptides (CPPs) are naturally able to cross the lipid bilayer membrane that protects cells. These peptides share common structural and physicochemical properties and show different pharmaceutical applications, among which drug delivery is the most important. Due to their ability to cross the membranes by pulling high-molecular-weight polar molecules, they are termed Trojan horses.

Targeting Peptidyl-prolyl Cis-trans Isomerase NIMA-interacting 1: A Structure-based Virtual Screening Approach to Find Novel Inhibitors.

Background: Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) is an enzyme that isomerizes phosphorylated serine or threonine motifs adjacent to proline residues. Pin1 has important roles in several cellular signaling pathways, consequently impacting the development of multiple types of cancers.

Methods: Based on the previously reported inhibitory activity of pentacyclic triterpenoids isolated from the gum resin of Boswellia genus against Pin1, we designed a computational experiment using molecular docking, pharmacophore filtering, and structural clustering allied to molecular dynamics (MD) simulations and binding free energy calculations to explore the inhibitory activity of new triterpenoids against Pin1 structure.

Insight into the Interaction Mechanism of Nicotine, NNK, and NNN with Cytochrome P450 2A13 Based on Molecular Dynamics Simulation.

Tobacco smoke contains various cancer-causing toxic substances, including nicotine and nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and '-nitrosonornicotine (NNN). The cytochrome 2A13 is involved in nicotine metabolism and in the activation of the pro-carcinogenic agents NNK and NNN, by means of α-hydroxylation reactions. Despite the significance of cytochrome 2A13 in the biotransformation of these molecules, its conformational mechanism and the molecular basis involved in the process are not fully understood.

Structural analysis of viral infectivity factor of HIV type 1 and its interaction with A3G, EloC and EloB.

Background: The virion infectivity factor (Vif) is an accessory protein, which is essential for HIV replication in host cells. Vif neutralizes the antiviral host protein APOBEC3 through recruitment of the E3 ubiquitin ligase complex.

Methodology: Fifty thousand Vif models were generated using the ab initio relax protocol of the Rosetta algorithm from sets of three- and nine-residue fragments using the fragment Monte Carlo insertion-simulated annealing strategy, which favors protein-like features, followed by an all-atom refinement.