Computational assessment of herbal medicine-derived compounds as potential inhibitors of SARS-CoV-2 main protease

Abstract

Since the main protease (Mpro) is crucial for the COVID-19 virus replication and transcription, searching for Mpro inhibitors is one possible treatment option. In our study, 258 small molecules were collected from lung-related herbal medicines, and their structures were optimized with the B3LYP-D3/6-31G* method. After the molecular docking with Mpro, we selected the top 20 compounds for the further geometry optimization with the larger basis sets. After the further molecular docking, the top eight compounds were screened out. Then we performed molecular dynamics simulations and binding free energy calculations to determine stability of the complexes. Our results show that mulberrofuran G, Xambioona, and kuwanon D can bind Mpro well. In quantum chemistry studies, such as ESP and CDFT analyses, the compounds properties are predicted. Additionally, the drug-likeness analyses and ADME studies on these three candidate compounds verified that all of them conform to Libinski’s rule and may be drug-like compounds.

Graphical Abstract

Communicated by Ramaswamy H. Sarma

KEYWORD:

• COVID-19
• SARS-CoV-2 Mpro
• molecular docking
• molecular dynamics simulation
• DFT

Disclosure statement

There are no conflicts to declare.

Correction Statement

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

Additional information

Funding

This research was funded by the National Natural Science Foundation of China (grants No. 10904111, 11604238), the Tianjin Natural Science Foundation (11JCYBJC14500), and the Science and Technology Development Fund of Tianjin Education Commission for Higher Education (2019KJ175).