Molecular docking identification for the efficacy of natural limonoids against COVID-19 virus main protease

Oliveira, Victor Moreira de; Marinho, Márcia Machado; Magalhães, Emanuel Paula; Menezes, Ramon Róseo Paula Pessoa Bezerra de; Sampaio, Tiago Lima; Martins, Alice Maria Costa; Santos, Hélcio Silva dos; Marinho, Emmanuel Silva

doi:10.1016/j.jics.2021.100157

Cited by 2 publications

(2 citation statements)

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“…Repurposed compounds could provide a scaffold for developing next generation highly efficient, low toxic new drugs. 25,26 Protein-ligand binding affinities involve enthalpic and entropic components, captured by the change in free energy between the complex and its substituents in equilibrium. Given the complexity of predicting potential inhibitors and analyzing their interactions with the active site, computational methods such as Molecular Dynamics are becoming increasingly important.…”

Section: Introductionmentioning

confidence: 99%

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SARS‐CoV‐2 main protease mutation analysis via a kinematic method

2023

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The Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS‐CoV‐2) is the virus responsible for the COVID‐19 pandemic. COVID‐19 continues to cause millions of deaths globally in part due to immune‐evading mutations. SARS‐CoV‐2 main protease (Mpro) is an important enzyme for viral replication and potentially an effective drug target. Mutations affect the dynamics of enzymes and thereby their activity and ability to bind ligands. Here, we use kinematic flexibility analysis (KFA) to identify how mutations and ligand binding changes the conformational flexibility of Mpro. KFA decomposes macromolecules into regions of different flexibility near‐instantly from a static structure, allowing conformational dynamics analysis at scale. Altogether, we analyzed 47 mutation sites across 69 Mpro–ligand complexes resulting in more than 3300 different structures which includes 69 mutated structures with all 47 sites mutated simultaneously and 3243 single residue mutated structures. We found that mutations generally increased the conformational flexibility of the protein. Understanding the impact of mutations on the flexibility of Mpro is essential for identifying potential drug targets in the treatment of SARS‐CoV‐2. Further studies in this area can offer valuable insights into the mechanisms of molecular recognition.

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Section: Introductionmentioning

confidence: 99%

“…Furthermore, limonoids and Remdesivir (RDS) were discovered as promising drugs to inhibit the SARS‐CoV‐2 Mpro. Repurposed compounds could provide a scaffold for developing next generation highly efficient, low toxic new drugs 25,26 …”

Section: Introductionmentioning

confidence: 99%