Simone Albani
A5054479673- Computational Drug Discovery Methods
- SARS-CoV-2 and COVID-19 Research
- Protein Structure and Dynamics
- Monoclonal and Polyclonal Antibodies Research
- Protein purification and stability
- Lipid Membrane Structure and Behavior
- Ion channel regulation and function
- Chemical Reactions and Isotopes
- Ion Transport and Channel Regulation
- vaccines and immunoinformatics approaches
- Synthesis and biological activity
- Neuroscience and Neuropharmacology Research
- Galectins and Cancer Biology
- Protein Tyrosine Phosphatases
- Receptor Mechanisms and Signaling
- Anesthesia and Sedative Agents
- RNA Interference and Gene Delivery
- Enzyme Production and Characterization
- Enzyme Structure and Function
- Semantic Web and Ontologies
- RNA and protein synthesis mechanisms
- Pain Mechanisms and Treatments
- Mosquito-borne diseases and control
- Click Chemistry and Applications
- Bacteriophages and microbial interactions
RWTH Aachen University
2020-2024
Forschungszentrum Jülich
2020-2024
University of Bologna
2023
University of Ferrara
2011
Compound repurposing is an important strategy for the identification of effective treatment options against SARS-CoV-2 infection and COVID-19 disease. In this regard, main protease (3CL-Pro), also termed M-Pro, attractive drug target as it plays a central role in viral replication by processing polyproteins pp1a pp1ab at multiple distinct cleavage sites. We here report results program involving 8.7 K compounds containing marketed drugs, clinical preclinical candidates, small molecules...
After almost two years from its first evidence, the COVID-19 pandemic continues to afflict people worldwide, highlighting need for multiple antiviral strategies. SARS-CoV-2 main protease (Mpro/3CLpro) is a recognized promising target development of effective drugs. Because single inhibition might not be sufficient block infection and replication, multi enzymatic-based therapies may provide better strategy. Here we present structural biochemical characterization binding mode MG-132 both...
The SARS-CoV-2 coronavirus outbreak continues to spread at a rapid rate worldwide. main protease (Mpro) is an attractive target for anti-COVID-19 agents. Unexpected difficulties have been encountered in the design of specific inhibitors. Here, by analyzing ensemble ∼30 000 Mpro conformations from crystallographic studies and molecular simulations, we show that small structural variations binding site dramatically impact ligand properties. Hence, traditional druggability indices fail...
The COVID-19 pandemic continues to pose a substantial threat human lives and is likely do so for years come. Despite the availability of vaccines, searching efficient small-molecule drugs that are widely available, including in low- middle-income countries, an ongoing challenge. In this work, we report results open science community effort, "Billion molecules against challenge", identify inhibitors SARS-CoV-2 or relevant receptors. Participating teams used wide variety computational methods...
The 3CL-Protease appears to be a very promising medicinal target develop anti-SARS-CoV-2 agents. availability of resolved structures allows structure-based computational approaches carried out even though the lack known inhibitors prevents proper validation performed simulations. innovative idea study is exploit SARS-CoV 3CL-Pro as training set perform and validate multiple virtual screening campaigns. Docking simulations using four different programs (Fred, Glide, LiGen, PLANTS) were...
Cholesterol is a major component of plasma membranes and plays significant role in actively regulating the functioning several membrane proteins humans. In this study, we focus on cholesterol depletion voltage-gated sodium channel Na
The only known peptide-gated ion channels—FaNaCs/WaNaCs and HyNaCs—belong to different clades of the DEG/ENaC family. FaNaCs are activated by short neuropeptide FMRFamide, HyNaCs Hydra RFamides, which not evolutionarily related FMRFamide. FMRFamide-binding site in was recently identified a cleft atop large extracellular domain. However, this is conserved HyNaCs. Here, we combined molecular modeling site-directed mutagenesis putative binding pocket for Hydra-RFamides domain heterotrimeric...
Many homodimeric enzymes tune their functions by exploiting either negative or positive cooperativity between subunits. In the SARS-CoV-2 Main protease (Mpro) homodimer, latter has been suggested symmetry in most of 500 reported protease/ligand complex structures solved macromolecular crystallography (MX). Here we apply to both covalent and noncovalent ligands with Mpro. Strikingly, our experiments show that occupation active sites dimer originates from an excess ligands. Indeed, cocrystals...
Many homodimeric enzymes tune their function by exploiting either negative or positive cooperativity between subunits. In the SARS-CoV-2 Main protease (Mpro) homodimer, latter has been suggested symmetry in most of 500 reported protease/ligand complex structures solved macromolecular crystallography. Here we apply to both covalent and non-covalent ligands with Mpro. Strikingly, our experiments show that occupation active sites dimer originates from an excess ligands. Indeed, co-crystals...
Abstract Compound repurposing is an important strategy for the identification of effective treatment options against SARS-CoV-2 infection and COVID-19 disease. In this regard, main protease (3CL-Pro), also termed M-Pro, attractive drug target as it plays a central role in viral replication by processing polyproteins pp1a pp1ab at multiple distinct cleavage sites. We here report results program involving 8.7 K compounds containing marketed drugs, clinical preclinical candidates, small...
Abstract Cholesterol is a major component of plasma membranes and unsurprisingly plays significant role in actively regulating the functioning several membrane proteins humans. Notably, recent studies have shown that cholesterol depletion can also impact transmission potentially painful signals context peripheral inflammation, via hyperexcitability voltage-gated sodium channel (Na v ) subtype 1.9, but structural mechanisms underlying this regulation remain to be elucidated. In study, we...
The COVID-19 pandemic continues to pose a substantial threat human lives and is likely do so for years come. Despite the availability of vaccines, searching efficient small-molecule drugs that are widely available, including in low- middle-income countries, an ongoing challenge. In this work, we report results community effort, “Billion molecules against Covid-19 challenge”, identify inhibitors SARS-CoV-2 or relevant receptors. Participating teams used wide variety computational methods...
Erwinia amylovora is a Gram-negative bacterium, responsible for the fire blight disease in Rosaceae plants. Its virulence correlated with production of an exopolysaccharide (EPS) called amylovoran, which protects bacterium from surrounding environment and helps its diffusion inside host. Amylovoran biosynthesis relies on expression twelve genes clustered ams operon. One these genes, amsI, encodes Low Molecular Weight Protein Tyrosine Phosphatase (LMW-PTP) EaAmsI, plays key role regulation...
Abstract The SARS-CoV-2 coronavirus outbreak continues to spread at a rapid rate worldwide. main protease (Mpro) is an attractive target for anti-COVID-19 agents. Unfortunately, unexpected difficulties have been encountered in the design of specific inhibitors. Here, by analyzing ensemble ~30,000 Mpro conformations from crystallographic studies and molecular simulations, we show that small structural variations binding site dramatically impact ligand properties. Hence, traditional...