An L-theanine derivative targets against SARS-CoV-2 and its Delta and Omicron variants

Jing Lu; Ying Zhang; Dan Qi; Chunyan Yan; Benhao Wu; Jason H Huang; Jianwen Yao; Erxi Wu; Guoying Zhang

doi:10.1016/j.heliyon.2022.e09660

An L-theanine derivative targets against SARS-CoV-2 and its Delta and Omicron variants

Heliyon. 2022 Jun;8(6):e09660. doi: 10.1016/j.heliyon.2022.e09660. Epub 2022 Jun 9.

Authors

Jing Lu¹, Ying Zhang^{1

2

3}, Dan Qi⁴, Chunyan Yan^{1

5}, Benhao Wu², Jason H Huang^{4

6}, Jianwen Yao¹, Erxi Wu^{4

6

7

8}, Guoying Zhang¹

Affiliations

¹ Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, School of Pharmacy, Yantai University, Yantai, Shandong, 264005, China.
² Shandong YingdongYinghao Biotechnology Inc., Yantai, Shandong, 264670, China.
³ Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND, 58105, USA.
⁴ Neuroscience Institute, Baylor Scott & White Health, Temple, Texas, 76502, USA.
⁵ Department of Pharmacy, Yantai Yuhuangding Hospital (Laishan branch), Yantai, Shandong, 264003, China.
⁶ College of Medicine, Texas A&M University, College Station, TX, 77843, USA.
⁷ College of Irma Lerma Rangel College of Pharmacy, Texas A&M University, College Station, TX, 77843, USA.
⁸ LIVESTRONG Cancer Institutes and Department of Oncology, Dell Medical School, The University of Texas at Austin, Austin, TX, 78712, USA.

Abstract

Recent research efforts have shown that tea has activities against SARS-CoV-2. However, the active compounds and the action mechanisms are largely unknown. Here we study the inhibitory potential of L-theanine from tea and its semi-synthesized derivative, a small-molecule fluorescent compound, ethyl 6-bromocoumarin-3-carboxylyl L-theanine (TBrC) against infection and replication of SARS-CoV-2 and the underlying mechanisms of action. We reveal that TBrC has potential activities against SARS-CoV-2 in addition to its activity against lung cancer. TBrC showed extracellular inhibition of SARS-CoV-2 M^pro/3CL and the host cell receptor ACE2 while interacting with the viral spike glycoproteins (wild-type, Delta, and Omicron mutants). Moreover, TBrC and L-theanine significantly suppressed growth and TNFα-induced nuclear transcriptional activation of NF-κB in human lung cancer cells without affecting the viability of normal lung cells, suggesting a potential protection of TBrC and L-theanine from pulmonary damages in SARS-CoV-2 infected patients, especially for lung cancer patients with SARS-CoV-2 infection.

Keywords: ACE2; Mpro/3CL; Mutant spike proteins; NF-κB; SARS-CoV-2; TBrC.