Publication detail

Identification of high-affinity inhibitors of SARS-CoV-2 main protease: Towards the development of effective COVID-19 therapy

MOHAMMAD, T. SHAMSI, A. ANWAR, S. UMAIR, M. HUSSAIN, A. REHMAN, T. ALAJMI, M. ISLAM, A. HASSAN, I.

Original Title

Identification of high-affinity inhibitors of SARS-CoV-2 main protease: Towards the development of effective COVID-19 therapy

Type

journal article in Web of Science

Language

English

Original Abstract

Coronavirus disease 2019 (COVID-19) is an infectious disease, caused by a newly emerged highly pathogenic virus called novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Targeting the main protease (M-pro, 3CL(pro)) of SARS-CoV-2 is an appealing approach for drug development because this enzyme plays a significant role in the viral replication and transcription. The available crystal structures of SARS-CoV-2 M-pro determined in the presence of different ligands and inhibitor-like compounds provide a platform for the quick development of selective inhibitors of SARS-CoV-2 M-pro. In this study, we utilized the structural information of co-crystallized SARS-CoV-2 M-pro for the structure-guided drug discovery of high-affinity inhibitors from the PubChem database. The screened compounds were selected on the basis of their physicochemical properties, drug-likeliness, and strength of affinity to the SARS-CoV-2 M-pro. Finally, we have identified 6-Deaminosinefungin (PubChem ID: 10428963) and UNII-O9H5KY11SV (PubChem ID: 71481120) as potential inhibitors of SARS-CoV-2 M-pro which may be further exploited in drug development to address SARS-CoV-2 pathogenesis. Both compounds are structural analogs of known antivirals, having considerable protease inhibitory potential with improved pharmacological properties. All-atom molecular dynamics simulations suggested SARS-CoV-2 M-pro in complex with these compounds is stable during the simulation period with minimal structural changes. This work provides enough evidence for further implementation of the identified compounds in the development of effective therapeutics of COVID-19.

Keywords

Coronavirus disease 2019; SARS-CoV-2; Main protease; Virtual screening; Molecular dynamics simulations; Drug discovery

Authors

MOHAMMAD, T.; SHAMSI, A.; ANWAR, S.; UMAIR, M.; HUSSAIN, A.; REHMAN, T.; ALAJMI, M.; ISLAM, A.; HASSAN, I.

Released

21. 8. 2020

Publisher

ELSEVIER

Location

AMSTERDAM

ISBN

1872-7492

Periodical

VIRUS RESEARCH

Year of study

288

State

Kingdom of the Netherlands

Pages count

9

BibTex

@article{BUT183367,
  author="Taj {Mohammad} and Anas {Shamsi} and Saleha {Anwar} and Mohammad {Umair} and Afzal {Hussain} and Tabish {Rehman} and Mohamed {AlAjmi} and Asimul {Islam} and Imtaiyaz {Hassan}",
  title="Identification of high-affinity inhibitors of SARS-CoV-2 main protease: Towards the development of effective COVID-19 therapy",
  journal="VIRUS RESEARCH",
  year="2020",
  volume="288",
  pages="9",
  doi="10.1016/j.virusres.2020.198102",
  issn="1872-7492"
}