Discovering Influenza Virus Neuraminidase Inhibitors via Computational and Experimental Studies.

Influenza A and B viruses spread out worldwide, causing several global concerns. Discovering neuraminidase inhibitors to prevent influenza A and B viruses is thus of great interest. In this work, a machine learning model was trained and tested to evaluate the ligand-binding affinity to neuraminidase.

A Combination of Blue Light at 460 nm and HO for the Safe and Effective Eradication of in an Infected Mouse Skin Abrasion Model.

Antibiotic-free approaches are more important than ever to address the rapidly growing problem of the antibiotic resistance crisis. The photolysis of the bacterial virulence factor staphyloxanthin using blue light at 460 nm (BL460 nm) has been found to effectively attenuate to chemical and physical agents. However, phototherapy using BL640 nm still needs to be investigated in detail for its safety in eradicating in vitro and in vivo.

Morphology of a Transmembrane Aβ Tetramer via REMD Simulations.

The folding/misfolding of membrane-permiable Amyloid beta (Aβ) peptides is likely associated with the advancing stage of Alzheimer's disease (AD) by disrupting Ca homeostasis. In this context, the aggregation of four transmembrane Aβ peptides was investigated using temperature replica-exchange molecular dynamics (REMD) simulations. The obtained results indicated that the secondary structure of transmembrane Aβ peptides tends to have different propensities compared to those in solution.

Upgrading nirmatrelvir to inhibit SARS-CoV-2 Mpro via DeepFrag and free energy calculations.

The first oral drug for the treatment of COVID-19, Paxlovid, has been authorized; however, nirmatrelvir, a major component of the drug, is reported to be associated with some side effects. Moreover, the appearance of many novel variants raises concerns about drug resistance, and designing new potent inhibitors to prevent viral replication is thus urgent. In this context, using a hybrid approach combining machine learning (ML) and free energy simulations, 6 compounds obtained by modifying nirmatrelvir were proposed to bind strongly to SARS-CoV-2 Mpro.

Characterizing the ligand-binding affinity toward SARS-CoV-2 Mpro physics- and knowledge-based approaches.

Computational approaches, including physics- and knowledge-based methods, have commonly been used to determine the ligand-binding affinity toward SARS-CoV-2 main protease (Mpro or 3CLpro). Strong binding ligands can thus be suggested as potential inhibitors for blocking the biological activity of the protease. In this context, this paper aims to provide a short review of computational approaches that have recently been applied in the search for inhibitor candidates of Mpro.

Searching for potential inhibitors of SARS-COV-2 main protease using supervised learning and perturbation calculations.

Inhibiting the biological activity of SARS-CoV-2 Mpro can prevent viral replication. In this context, a hybrid approach using knowledge- and physics-based methods was proposed to characterize potential inhibitors for SARS-CoV-2 Mpro. Initially, supervised machine learning (ML) models were trained to predict a ligand-binding affinity of ca.

Distal Hydrophobic Loop Modulates the Copper Active Site and Reaction of AA13 Polysaccharide Monooxygenases.

Polysaccharide monooxygenases (PMOs) use a type-2 copper center to activate O for the selective hydroxylation of one of the two C-H bonds of glycosidic linkages. Our electron paramagnetic resonance (EPR) analysis and molecular dynamics (MD) simulations suggest the unprecedented dynamic roles of the loop containing the residue G89 (G89 loop) on the active site structure and reaction cycle of starch-active PMOs (AA13 PMOs). In the Cu(II) state, the G89 loop could switch between an "open" and "closed" conformation, which is associated with the binding and dissociation of an aqueous ligand in the distal site, respectively.

Transcriptomic and Ultrastructural Analyses of Treated With Fungicidal Peptaibol Analogs of Trichogin.

Eco-friendly analogs of Trichogin GA IV, a short peptaibol produced by , were assayed against , the causal agent of rice blast disease. and screenings allowed us to identify six peptides able to reduce by about 70% rice blast symptoms. One of the most active peptides was selected for further studies.

Improving ligand-ranking of AutoDock Vina by changing the empirical parameters.

AutoDock Vina (Vina) achieved a very high docking-success rate, , but give a rather low correlation coefficient, , for binding affinity with respect to experiments. This low correlation can be an obstacle for ranking of ligand-binding affinity, which is the main objective of docking simulations. In this context, we evaluated the dependence of Vina R coefficient upon its empirical parameters.

Binding of inhibitors to the monomeric and dimeric SARS-CoV-2 Mpro.

SARS-CoV-2 rapidly infects millions of people worldwide since December 2019. There is still no effective treatment for the virus, resulting in the death of more than one million patients. Inhibiting the activity of SARS-CoV-2 main protease (Mpro), 3C-like protease (3CLP), is able to block the viral replication and proliferation.

Computational investigation of possible inhibitors of the winged-helix domain of MUS81.

The methyl methanesulfonate and ultraviolet sensitive 81 (MUS81) is a structure-specific endonuclease that is highly conserved in eukaryotes and essential for homologous recombination repair. The winged-helix domain at the N-terminus of MUS81 (wMUS81) can bind DNA substrates and regulate the endonuclease activity. The repression of MUS81 activity could enhance the sensitivity to antitumor compounds of different tumour cells.

Assessing potential inhibitors of SARS-CoV-2 main protease from available drugs using free energy perturbation simulations.

The main protease (Mpro) of the novel coronavirus SARS-CoV-2, which has caused the COVID-19 pandemic, is responsible for the maturation of its key proteins. Thus, inhibiting SARS-CoV-2 Mpro could prevent SARS-CoV-2 from multiplying. Because new inhibitors require thorough validation, repurposing current drugs could help reduce the validation process.

Direct colorimetric LAMP assay for rapid detection of African swine fever virus: A validation study during an outbreak in Vietnam.

African swine fever (ASF) is a highly infectious viral disease with high mortality. The most recent ASF outbreak in Vietnam began in 2019, posing a threat to spread to the neighbouring Asian countries. Without a commercial vaccine or efficient chemotherapeutics, rapid diagnosis and necessary biosecurity procedures are required to control the disease.

Rapid prediction of possible inhibitors for SARS-CoV-2 main protease using docking and FPL simulations.

Originating for the first time in Wuhan, China, the outbreak of SARS-CoV-2 has caused a serious global health issue. An effective treatment for SARS-CoV-2 is still unavailable. Therefore, in this study, we have tried to predict a list of potential inhibitors for SARS-CoV-2 main protease (Mpro) using a combination of molecular docking and fast pulling of ligand (FPL) simulations.

Computational Determination of Potential Inhibitors of SARS-CoV-2 Main Protease.

The novel coronavirus (SARS-CoV-2) has infected several million people and caused thousands of deaths worldwide since December 2019. As the disease is spreading rapidly all over the world, it is urgent to find effective drugs to treat the virus. The main protease (Mpro) of SARS-CoV-2 is one of the potential drug targets.

Nano-plastics and their analytical characterisation and fate in the marine environment: From source to sea.

Polymer contamination is a major pollutant in all waterways and a significant concern of the 21st Century, gaining extensive research, media, and public attention. The polymer pollution problem is so vast; plastics are now observed in some of the Earth's most remote regions such as the Mariana trench. These polymers enter the waterways, migrate, breakdown; albeit slowly, and then interact with the environment and the surrounding biodiversity.

Impact of the Astaxanthin, Betanin, and EGCG Compounds on Small Oligomers of Amyloid Aβ Peptide.

There is experimental evidence that the astaxanthin, betanin, and epigallocatechin-3-gallate (EGCG) compounds slow down the aggregation kinetics and the toxicity of the amyloid-β (Aβ) peptide. How these inhibitors affect the self-assembly at the atomic level remains elusive. To address this issue, we have performed for each ligand atomistic replica exchange molecular dynamic (REMD) simulations in an explicit solvent of the Aβ trimer from the U-shape conformation and MD simulations starting from Aβ dimer and tetramer structures characterized by different intra- and interpeptide conformations.

Fine Tuning of the Copper Active Site in Polysaccharide Monooxygenases.

Type 2 copper active sites, one of the several important copper active sites in biology, were recently found in the novel superfamily of polysaccharide monooxygenases (PMOs) that cleave recalcitrant polysaccharides via an unprecedented oxidative mechanism. The copper center in PMOs is ligated by the bidentate N-terminal histidine residue and another conserved histidine residue, forming a unique T-shaped core termed as . This core serves as the foundation for diverse structures and electronic properties among PMO families and subfamilies.

Autodock Vina Adopts More Accurate Binding Poses but Autodock4 Forms Better Binding Affinity.

The binding pose and affinity between a ligand and enzyme are very important pieces of information for computer-aided drug design. In the initial stage of a drug discovery project, this information is often obtained by using molecular docking methods. Autodock4 and Autodock Vina are two commonly used open-source and free software tools to perform this task, and each has been cited more than 6000 times in the last ten years.

Oversampling Free Energy Perturbation Simulation in Determination of the Ligand-Binding Free Energy.

Determination of the ligand-binding affinity is an extremely interesting problem. Normally, the free energy perturbation (FEP) method provides an appropriate result. However, it is of great interest to improve the accuracy and precision of this method.

C-Terminal Plays as the Possible Nucleation of the Self-Aggregation of the S-Shape Aβ Tetramer in Solution: Intensive MD Study.

Amyloid beta (Aβ) peptides are characterized as the major factors associated with neuron death in Alzheimer's disease, which is listed as the most common form of neurodegeneration. Disordered Aβ peptides are released from proteolysis of the amyloid precursor protein. The Aβ self-assembly process roughly takes place via five steps: disordered forms → oligomers → photofibrils → mature fibrils → plaques.

Effective Estimation of Ligand-Binding Affinity Using Biased Sampling Method.

The binding between two biomolecules is one of the most critical factors controlling many bioprocesses. Therefore, it is of great interest to derive a reliable method to calculate the free binding energy between two biomolecules. In this work, we have demonstrated that the binding affinity of ligands to proteins can be determined through biased sampling simulations.

Interaction of carbohydrate binding module 20 with starch substrates.

CBM20s are starch-binding domains found in many amylolytic enzymes, including glucoamylase, alpha-amylase, beta-amylases, and a new family of starch-active polysaccharide monooxygenases (AA13 PMOs). Previous studies of CBM20-substrate interaction only concerned relatively small or soluble amylose molecules, while amylolytic enzymes often work on extended chains of insoluble starch molecules. In this study, we utilized molecular simulation techniques to gain further insights into the interaction of CBM20 with substrates of various sizes its two separate binding sites, termed as BdS1 and BdS2.

Substrate selectivity in starch polysaccharide monooxygenases.

Degradation of polysaccharides is central to numerous biological and industrial processes. Starch-active polysaccharide monooxygenases (AA13 PMOs) oxidatively degrade starch and can potentially be used with industrial amylases to convert starch into a fermentable carbohydrate. The oxidative activities of the starch-active PMOs from the fungi and , AA13 and AA13, respectively, on three different starch substrates are reported here.