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Suntrap’s research team found that LeSoleil-T exerts ef- quelae caused by SARS-CoV-2 infection include ner-
fects against SARS-CoV-2 through directly inhibition of vous system damage, pneumonia-induced lung fibro-
the activity of TMPRSS2 and M (also known as 3CL ). sis, cardiomyocyte damage, liver and kidney damage.
pro
pro
As known, TMPRSS2 and M are involved in SARS-CoV-2 In response to the nervous system damage caused by
pro
replication and infection. For one thing, LeSoleil-T inhib- SARS-CoV-2, LeSoleil-T showed neuroprotective effects
its the activation of spike protein by TMPRSS2 and blocks by regulating the expression of related proteins and re-
the entry of the SARS-CoV-2 virus into the host cell. For ducing the stress response. Detailed mechanisms are as
another, it inhibits the M of SARS-CoV-2 to suppress follows: (1) It can reduce inflammatory to prevent cell
pro
its replication. In addition, M exists in various coro- damage and protect neurons; (2) LeSoleil-T can activate
pro
naviruses, which contribute to the broad-spectrum an- NF-κB (Nuclear factor kappa B) to inhibit the inflamma-
ti-coronavirus characteristic of LeSoleil-T by its inhibition tion of microglia and the proliferation of microglia and
of M protein. astrocytes to protect neurons; (3) LeSoleil-T can protect
pro
neurons by inhibiting the expression of c-fos and c-jun,
According to clinical investigations, upon SARS-CoV-2
and regulating the expression of Bax (pro apoptotic fac-
infection, the levels of the neutrophil count, D-dimer,
tor), Bcl-2 (inhibitor of apoptosis) and caspase-3 (termi-
blood urea and creatinine in patients will increase
nal shear enzyme of apoptosis); and (4) LeSoleil-T can
continuously, while the count of lymphocytes will con-
reconstruct the expression of Akt and pAkt in the cere-
tinue to decline until death. Suntrap team found that
bral cortex, to maintain the levels of Akt and pAkt, and
LeSoleil-T could eliminate inflammation induced by
to promote neuronal survival.
SARS-CoV-2 infection. The anti-inflammatory effects of
LeSoleil-T are mainly to inhibit proinflammatory factor In terms of pulmonary fibrosis caused by COVID-19, the
expression and reduce oxidative stress responses. Firstly, Suntrap research team uncovered that LeSoleil-T can
LeSoleil-T can inhibit neutrophil aggregation to reduce reduce the protein expression of iNOS (Inducible nitric
the production of 4-HNE (4-hydroxynonenal) by oxida- oxide synthase) in vivo and in vitro, resulting in reducing
tive stress response, which leads to the reduction of the the combination of NO and free radicals to form RNS, the
lipid peroxidation end-product formation, and finally, stress reaction of the nitro, lung injury, and pulmonary
contribute to its anti-inflammatory activity. Secondly, Le- fibrosis. Besides, LeSoleil-T can inhibit TGF-β1-mediat-
Soleil-T directly inhibits the expression of proinflamma- ed EMT (Epithelial-mesenchymal transition) signaling
tory factors (e.g., Tnf-α, IL-1β, IL-6, Mcp-1, Mcp-2, and pathway and reduce the phosphorylation of SMAD2/3,
Mip-1α). Finally, it activates the interactions among PGC- decrease ERK1/2 (extracellular signal-regulated kinase)
1α (Peroxisome proliferator-activated receptor-γ coacti- and activate the SMAD signal, the protein expression of
vator), Nrf1 (Nuclear Respiratory Factor 1) and Nrf2 (Nu- Coll and Timp, upregulate the expression of MMP (ma-
clear Respiratory Factor 2) to regulate the mitochondrial trix metalloproteinase), reduce the expression of ECM
synthesis, respiration, and various antioxidant enzymes. (extracellular matrix), prevent the ECM from accumulat-
Meanwhile, the Nrf2/ARE (antioxidant response ele- ing excessively, reduce myofibroblast formation, repair
ment) complex scavenges free radicals by regulating the the damaged tissue, delay and reverse pulmonary fibro-
expression of HO-1 (heme oxygenase-1). sis.

According to the clinical studies on COVID-19, the se- Based on the clinical symptoms and pathogenic mecha-