Exploration of the anti-SARS-CoV-2 potential and expected mechanisms of small molecules from Antrodia cinnamomea by BT&D2 drug-targeting analysis
Issued Date
2025-08-01
Resource Type
ISSN
00452068
eISSN
10902120
Scopus ID
2-s2.0-105007456864
Journal Title
Bioorganic Chemistry
Volume
163
Rights Holder(s)
SCOPUS
Bibliographic Citation
Bioorganic Chemistry Vol.163 (2025)
Suggested Citation
Singh A., Xu S.H., Tsai Y.D., Yang Z.S., Tang H.J., Tsai Y.J., Tsai H.Y., Yuan C.W., Chen C.C., Thitithanyanont A., Wang S.F., Chiu H.T. Exploration of the anti-SARS-CoV-2 potential and expected mechanisms of small molecules from Antrodia cinnamomea by BT&D2 drug-targeting analysis. Bioorganic Chemistry Vol.163 (2025). doi:10.1016/j.bioorg.2025.108646 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/110682
Title
Exploration of the anti-SARS-CoV-2 potential and expected mechanisms of small molecules from Antrodia cinnamomea by BT&D2 drug-targeting analysis
Corresponding Author(s)
Other Contributor(s)
Abstract
Severe diseases like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak urge efficient discovery of drugs for emergent needs and precision medicine. This study demonstrates an interdisciplinary solution by identification of a chief anti-SARS-CoV-2 small molecule, 2,3,5,8-tetrahydroxy-6-methylnaphthalene-1,4-dione (TMD) from a Taiwanese traditional medicine, Antrodia cinnamomea. TMD was found to inhibit the key viral replication enzymes, 3-chymotrypsin-like protease (3CLpro) and papain-like protease (PLpro), by structure-based prediction analysis using the Explore program of BT&D<sup>2</sup> drug targeting system. Subsequently, TMD was total-synthesized and shown to inhibit Omicron BA.2 and BA.5 variants. The enzymatic inhibition kinetics studies revealed the competitive inhibition and dual-target nature of TMD and its potential capability to target the proteases in mixed-type mode, consistent with the in silico mechanistic analysis. The predicted less off-target side effects of TMD also agreed with the animal toxicity test result of no apparent toxicity. This study provides new insight into anti-viral mechanism of Antrodia cinnamomea and a new lead drug with improved pharmacokinetics to combat SARS-CoV-2 infection.