Artesunate induces substantial topological alterations in the SARS-CoV-2 Nsp1 protein structure

Arun Bahadur Gurung; Mohammad Ajmal Ali; Joongku Lee; Mohammad Abul Farah; Khalid Mashay Al-Anazi; Fahad Al-Hemaid

doi:10.1016/j.jksus.2021.101810

Artesunate induces substantial topological alterations in the SARS-CoV-2 Nsp1 protein structure

J King Saud Univ Sci. 2022 Feb;34(2):101810. doi: 10.1016/j.jksus.2021.101810. Epub 2022 Jan 3.

Authors

Arun Bahadur Gurung¹, Mohammad Ajmal Ali², Joongku Lee³, Mohammad Abul Farah⁴, Khalid Mashay Al-Anazi⁴, Fahad Al-Hemaid²

Affiliations

¹ Department of Basic Sciences and Social Sciences, North-Eastern Hill University, Shillong 793022, Meghalaya, India.
² Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
³ Department of Environment and Forest Resources, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Republic of Korea.
⁴ Department of Zoology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.

Abstract

The need for novel antiviral treatments for coronavirus disease 2019 (COVID-19) continues with the widespread infections and fatalities throughout the world. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the deadly disease, relies on the non-structural protein Nsp1 for multiplication within the host cells and disarms the host immune defences by various mechanisms. Herein, we investigated the potential of artemisinin and its derivatives as possible inhibitors of SARS-CoV-2 Nsp1 through various computational approaches. Molecular docking results show that artemisinin (CID68827) binds to Nsp1 with a binding energy of -6.53 kcal/mol and an inhibition constant of 16.43 µM. The top 3 derivatives Artesunate (CID6917864), Artemiside (CID53323323) and Artemisone (CID11531457) show binding energies of -7.92 kcal/mol, -7.46 kcal/mol and -7.36 kcal/mol respectively. Hydrophobic interactions and hydrogen bonding with Val10, Arg11, and Gln50 helped to stabilize the protein-ligand complexes. The pharmacokinetic properties of these molecules show acceptable properties. The geometric parameters derived from large-scale MD simulation studies provided insights into the changes in the structural topology of Nsp1 upon binding of Artesunate. Thus, the findings of our research highlight the importance of artemisinin and its derivatives in the development of drugs to inhibit SARS-CoV-2 Nsp1 protein.

Keywords: Artemisinin; Artemisinin derivatives; Artesunate; COVID-19; Nsp1; SARS-CoV-2.