Insighting isatin derivatives as potential antiviral agents against NSP3 of COVID-19

Mubashar Ilyas; Shabbir Muhammad; Javed Iqbal; Saniyah Amin; Abdullah G Al-Sehemi; H Algarni; Saleh S Alarfaji; Mohammad Y Alshahrani; Khurshid Ayub

doi:10.1007/s11696-022-02298-7

Insighting isatin derivatives as potential antiviral agents against NSP3 of COVID-19

Chem Zvesti. 2022;76(10):6271-6285. doi: 10.1007/s11696-022-02298-7. Epub 2022 Jun 22.

Authors

Mubashar Ilyas¹, Shabbir Muhammad², Javed Iqbal¹, Saniyah Amin¹, Abdullah G Al-Sehemi², H Algarni³, Saleh S Alarfaji¹, Mohammad Y Alshahrani⁴, Khurshid Ayub⁵

Affiliations

¹ Department of Chemistry, University of Agriculture, Faisalabad, 38000 Pakistan.
² Department of Chemistry, College of Science, King Khalid University, P.O. Box 9004, Abha, 61413 Saudi Arabia.
³ Department of Physics, College of Science, King Khalid University, P.O. Box 9004, Abha, 61413 Saudi Arabia.
⁴ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, P.O. Box 61413, Abha, 9088 Saudi Arabia.
⁵ Department of Chemistry, COMSATS University, Abbottabad Campus, 22060 Pakistan.

Abstract

The world is now facing intolerable damage in all sectors of life because of the deadly COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2. The discovery and development of anti-SARS-CoV-2 drugs have become pragmatic in the time needed to fight against this pandemic. The non-structural protein 3 is essential for the replication of transcriptase complex (RTC) and may be regarded as a possible target against SARS-CoV-2. Here, we have used a comprehensive in silico technique to find potent drug molecules against the NSP3 receptor of SARS-CoV-2. Virtual screening of 150 Isatin derivatives taken from PubChem was performed based on their binding affinity estimated by docking simulations, resulting in the selection of 46 ligands having binding energy greater than -7.1 kcal/mol. Moreover, the molecular interactions of the nine best-docked ligands having a binding energy of ≥ -8.5 kcal/mol were analyzed. The molecular interactions showed that the three ligands (S5, S16, and S42) were stabilized by forming hydrogen bonds and other significant interactions. Molecular dynamic simulations were performed to mimic an in vitro protein-like aqueous environment and to check the stability of the best three ligands and NSP3 complexes in an aqueous environment. The binding energy of the S5, S16, and S42 systems obtained from the molecular mechanics Poisson-Boltzmann surface area also favor the system's stability. The MD and MM/PBSA results explore that S5, S16, and S42 are more stable and can be considered more potent drug candidates against COVID-19 disease.

Supplementary information: The online version contains supplementary material available at 10.1007/s11696-022-02298-7.

Keywords: Isatin derivatives; Molecular docking; Molecular dynamics; NSP3; SARS-CoV-2.