Asset Details
Do you wish to reserve the book?
Identification of potent multi-target antiviral natural compounds from the fungal metabolites against aspartyl viral polymerases
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Identification of potent multi-target antiviral natural compounds from the fungal metabolites against aspartyl viral polymerases
Do you wish to request the book?
Identification of potent multi-target antiviral natural compounds from the fungal metabolites against aspartyl viral polymerases
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Identification of potent multi-target antiviral natural compounds from the fungal metabolites against aspartyl viral polymerases
2025
Overview
Since viral polymerases are responsible for viral replication, they are a prime target in antiviral drug development. The present study evaluated the antiviral potential of 174 secondary metabolites of the Sordariales order against aspartyl polymerases, including hepatitis C virus nonstructural protein 5B (HCV NS5B) and Severe acute respiratory syndrome coronavirus 2 RNA-dependent RNA polymerase (SARS CoV-2 RdRp). A two-step virtual screening was performed, identifying 76 ligands binding to the active site, while 10 showed binding energies below -7 kcal/mol. Ligands 1–3 exhibited better binding affinities than the Ribavirin. Lig-3 demonstrated the most intense interaction. These interacted through hydrogen bonding and hydrophobic interactions with the key catalytic motifs that may disrupt viral replication by inhibiting polymerase activities. Next, the effects of these ligands induced in polymerase structure and dynamics were analyzed by 300 ns molecular dynamics (MD) simulations, showing that ligand binding altered structural dynamics in critical motifs responsible for NTP and RNA template binding. RMSF and PCA analyses revealed reduced protein mobility and significant structural destabilization, particularly for Lig-1 and Lig-3 in SARS-CoV-2 RdRp and Lig-2 and Lig-3 in HCV NS5B. Additionally, Rg and SASA analyses indicated structural compression in ligand-bound complexes, corroborating the hypothesis of enzymatic inhibition. MM/PBSA analysis highlighted Lig-1 and Lig-3 as having stronger binding energies for SARS-CoV-2 RdRp, while Lig-3 and Lig-2 displayed higher binding energies for HCV NS5B. With promising ADME/T properties, Lig-3 is a promising multi-target antiviral candidate against HCV NS5B and SARS-CoV-2 RdRp, meriting further in vitro and in vivo investigations.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ Antiviral Agents - chemistry
/ Antiviral Agents - pharmacology
/ Biological Products - chemistry
/ Biological Products - pharmacology
/ Coronavirus RNA-Dependent RNA Polymerase - antagonists & inhibitors
/ Coronavirus RNA-Dependent RNA Polymerase - chemistry
/ Coronavirus RNA-Dependent RNA Polymerase - metabolism
/ COVID-19
/ Humanities and Social Sciences
/ Humans
/ Ligands
/ Molecular Docking Simulation
/ Molecular Dynamics Simulation
/ RNA-Dependent RNA Polymerase - antagonists & inhibitors
/ Science
/ Severe acute respiratory syndrome coronavirus 2
/ Viral Nonstructural Proteins - antagonists & inhibitors
/ Viral Nonstructural Proteins - chemistry
