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Journals / Turkish Computational and Theoretical Chemistry / 2023 / Cilt: 7 - Sayı: 1

An in silico investigation of allosteric inhibition potential of Dihydroergotamine against Sars-CoV-2 Main Protease (MPro)

Mehmet Murat YAŞAR
Ekrem YAŞAR
Nuri YORULMAZ
Emin TENEKECİ
İsmail Hakkı SARPÜN
Erol EROĞLU
Pages
14–36
Publication Date
2023-01-15
DOI
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Considering the role of CYS145 in the catalytic cycle, this structural change is likely to be a mechanism for inhibiting MPro.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Possible allosteric inhibitors of MPro were investigated using in silico methods.
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Key Findings & Data:The allosteric inhibition potential of DHE toward MPro was demonstrated by applying some computational tools on the trajectory files which were obtained from the Molecular Dynamics Simulations.
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Conclusion & Impact:Considering the role of CYS145 in the catalytic cycle, this structural change is likely to be a mechanism for inhibiting MPro.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:MPro · Main Protease · allosteric inhibition

Abstract

Possible allosteric inhibitors of MPro were investigated using in silico methods. To this end, FDA-approved drugs in the DrugBank database were subjected to virtual screening, and drugs that strongly bind distant from the catalytic site of MPro were identified using molecular docking. Among the identified drugs, Dihydroergotamine (DHE) was chosen for further investigation due to its highest binding score against MPro in the molecular docking experiment. The allosteric inhibition potential of DHE toward MPro was demonstrated by applying some computational tools on the trajectory files which were obtained from the Molecular Dynamics Simulations. Results support that the hydrogen bonding interactions of DHE with GLU278 and THR280, located between Protomer A and Protomer B, affect the structure of the side chain of CYS145 at the catalytic site of MPro. Considering the role of CYS145 in the catalytic cycle, this structural change is likely to be a mechanism for inhibiting MPro.

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Cite This Article

YAŞAR, M. M., YAŞAR, E., YORULMAZ, N., TENEKECİ, E., SARPÜN, İ. H., EROĞLU, E. (2023). An in silico investigation of allosteric inhibition potential of Dihydroergotamine against Sars-CoV-2 Main Protease (MPro). Turkish Computational and Theoretical Chemistry, Cilt: 7 - Sayı: 1, 14–36. https://ajindex.com/articles/879265

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