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

Year 2023, , 14 - 36, 15.01.2023

Mehmet Murat Yaşar , Ekrem Yaşar , Nuri Yorulmaz , Emin Tenekeci , İsmail Hakkı Sarpün , Erol Eroğlu

https://doi.org/10.33435/tcandtc.1121985

Cited By: 1

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.

Keywords

MPro, Main Protease, allosteric inhibition, Dihydroergotamine

Thanks

This project was supported by Akdeniz University Scientific Research Projects Coordination Unit. Project ID:5408. The authors acknowledge Harran University High-Performance Computing Center for making computing resources available to us.

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