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.