Exploring the Traditional Chinese Medicine (TCM) database chemical space to target I7L protease from monkeypox virus using molecular screening and simulation approaches

ABSTRACT

In the current study, we used molecular screening and simulation approaches to target I7L protease from monkeypox virus (mpox) from the Traditional Chinese Medicines (TCM) database. Using molecular screening, only four hits TCM27763, TCM33057, TCM34450 and TCM31564 demonstrated better pharmacological potential than TTP6171 (control). Binding of these molecules targeted Trp168, Asn171, Arg196, Cys237, Ser240, Trp242, Glu325, Ser326, and Cys328 residues and may affect the function of I7L protease in in vitro assay. Moreover, molecular simulation revealed stable dynamics, tighter structural packing and less flexible behaviour for all the complexes. We further reported that the average hydrogen bonds in TCM27763, TCM33057, TCM34450 and TCM31564I7L complexes remained higher than the control drug. Finally, the BF energy results revealed −62.60 ± 0.65 for the controlI7L complex, for the TCM27763I7L complex −71.92 ± 0.70 kcal/mol, for the TCM33057I7L complex the BF energy was −70.94 ± 0.70 kcal/mol, for the TCM34450I7L the BF energy was −69.94 ± 0.85 kcal/mol while for the TCM31564I7L complex the BF energy was calculated to be −69.16 ± 0.80 kcal/mol. Although, we used stateoftheart computational methods, these are theoretical insights that need further experimental validation.

KEYWORDS:

• Monkeypox
• I7L protease
• virtual screening
• molecular simulation
• binding free energy

Acknowledgements

The computations were partially performed at the Center for High-Performance Computing of Shanghai Jiao Tong University and Pengcheng Lab. Authors are also thankful to the Researchers Supporting Project number (RSP2023R491), King Saud University, Riyadh, Saudi Arabia.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All the data is available on RCSB, UniProt and any simulation data would be provided on reasonable demand. The accession numbers to access this data are given in the manuscript.

Supplementary material

Supplemental data for this article can be accessed at: https://doi.org/10.1080/1062936X.2023.2250723

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

Dong-Qing Wei is supported by grants from the Key Research Area Grant [2016YFA0501703] of the Ministry of Science and Technology of China, the National Science Foundation of China [Grant No. 32070662, 61832019, 32030063], the Science and Technology Commission of Shanghai Municipality [Grant No: 19430750600], as well as SJTU JiRLMDS Joint Research Fund and Joint Research Funds for Medical and Engineering and Scientific Research at Shanghai Jiao Tong University [YG2021ZD02].