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
Affiliations
Jing Lu
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
Ying Zhang
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; Shandong YingdongYinghao Biotechnology Inc., Yantai, Shandong, 264670, China; Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND, 58105, USA
Dan Qi
Neuroscience Institute, Baylor Scott & White Health, Temple, Texas, 76502, USA
Chunyan Yan
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; Department of Pharmacy, Yantai Yuhuangding Hospital (Laishan branch), Yantai, Shandong, 264003, China
Benhao Wu
Shandong YingdongYinghao Biotechnology Inc., Yantai, Shandong, 264670, China
Jason H. Huang
Neuroscience Institute, Baylor Scott & White Health, Temple, Texas, 76502, USA; College of Medicine, Texas A&M University, College Station, TX, 77843, USA
Jianwen Yao
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; Corresponding author.
Erxi Wu
Neuroscience Institute, Baylor Scott & White Health, Temple, Texas, 76502, USA; College of Medicine, Texas A&M University, College Station, TX, 77843, USA; College of Irma Lerma Rangel College of Pharmacy, Texas A&M University, College Station, TX, 77843, USA; LIVESTRONG Cancer Institutes and Department of Oncology, Dell Medical School, The University of Texas at Austin, Austin, TX, 78712, USA; Corresponding author.
Guoying Zhang
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; Corresponding author.
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 Mpro/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.
