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Planta Med 2022; 88(12): 1047-1059
DOI: 10.1055/a-1581-3707
Biological and Pharmacological Activity
Original Papers

Activity of THC, CBD, and CBN on Human ACE2 and SARS-CoV1/2 Main Protease to Understand Antiviral Defense Mechanism

Thanet Pitakbut 
1   Technical Biochemistry, Faculty of Biochemical and Chemical Engineering, TU Dortmund University, Dortmund, Germany
,
Gia-Nam Nguyen 
1   Technical Biochemistry, Faculty of Biochemical and Chemical Engineering, TU Dortmund University, Dortmund, Germany
2   MINDbioscience GmbH, Dortmund, Germany
,
Oliver Kayser 
1   Technical Biochemistry, Faculty of Biochemical and Chemical Engineering, TU Dortmund University, Dortmund, Germany
› Author AffiliationsSupported by: Deutscher Akademischer Austauschdienst 57299294
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Abstract

THC, CBD, and CBN were reported as promising candidates against SARS-CoV2 infection, but the mechanism of action of these three cannabinoids is not understood. This study aims to determine the mechanism of action of THC, CBD, and CBN by selecting two essential targets that directly affect the coronavirus infections as viral main proteases and human angiotensin-converting enzyme2. Tested THC and CBD presented a dual-action action against both selected targets. Only CBD acted as a potent viral main protease inhibitor at the IC50 value of 1.86 ± 0.04 µM and exhibited only moderate activity against human angiotensin-converting enzyme2 at the IC50 value of 14.65 ± 0.47 µM. THC acted as a moderate inhibitor against both viral main protease and human angiotensin-converting enzymes2 at the IC50 value of 16.23 ± 1.71 µM and 11.47 ± 3.60 µM, respectively. Here, we discuss cannabinoid-associated antiviral activity mechanisms based on in silico docking studies and in vitro receptor binding studies.

Key words

Δ-9-Tetrahydrocannabinol - Cannabidiol - Cannabinol - coronavirus main protease1/2 - human angiotensin-converting enzyme2 - Cannabis sativa - Cannabaceae

Supporting Information

    We provided five supporting information incorporated with this study, such as Fig. 1S: Chemical structure of the cannabinoids (CBD) left, Δ9-tetrahydrocannabinol (THC) middle, and cannabinol (CBN) right, Fig. 2S: Chemical synthesis of CBN (all details see Material and Methods), Fig. 3S: 1H-NMR of CBN (all details see Material and Methods), Fig. 4S: 13C-NMR of CBN (all details see Material and Methods), Fig. 5S: Validation result of SARS-CoV2 main protease (all details see Material and Methods), Fig. 6S: Validation result of hACE2 (all details see Material and Methods), Fig. 7S: Chemical structure of GC376 and its IUPAC name, Fig. 8S: Chemical structure of MLN-4760 and its IUPAC name.

  • Supporting Information


Publication History

Received: 01 May 2021

Accepted after revision: 03 August 2021

Article published online:
12 October 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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