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Microbes & Immunity RANTES/CCL5 and ezrin peptide RepG3 for long COVID

lung epithelial organoids, the targeting of p38 MAPK signal
transduction with highly selective inhibitors of p38 MAPK
α/β isoforms, PH-797804 (Pfizer), and VX-702 (Vertex)
heavily suppresses the expression of the proinflammatory
cytokines IL-6, CXCL8, CXCL10, and TNF-α. 17

2. Ezrin peptide treatment in a long COVID/
vaccine injury volunteer patient
Male patient G had been struggling with long COVID-
associated bowel inflammation, breathlessness, and fatigue
since early 2021. His symptoms were worsened by an
mRNA COVID vaccine booster-shot in early 2022. RepG3
GEKKRRETVEREGG is a 14-amino acid synthetic ezrin
peptide (NH GlyGluLysLysArgArgGluThrValGluArgGlu
2
GlyGlyCOOH) with a molecular weight of 1630.76
Da. Treatment with oral spray-inhaled ezrin peptide
RepG3 2 mg/mL aqueous solution (2 mg/day for 5 days)
in October 2022 reduced his fatigue, dizziness, and
breathlessness and improved his general health. Patient
G underwent a second course of RepG3 treatment in
January 2023. In July 2023, after another relapse, patient-G
underwent a third course of RepG3 treatment.
Before the third course of ezrin peptide RepG3, Figure 1. Efficacy of ezrin peptide RepG3 in inhibiting inflammatory
the elevation above the reference limits for some cytokine and chemokine expression. Efficacy of ezrin peptide
proinflammatory cytokines and chemokines in patient G RepG3 (2 mg/day) in inhibiting inflammatory cytokine and chemokine
was very significant. For example, IL-13, which induces T expression in a long COVID/vaccine injury patient before and after
10 days of spray-inhalation therapy.
helper cell type 2 inflammation, is upregulated 17 folds. Abbreviations: GM-CSF: Granulocyte macrophage colony-stimulating
In addition, the elevation of macrophage inflammatory factor; IL: Interleukin; MIP: Macrophage inflammatory protein.
protein 1α (MIP-1α) was over 4 folds, and MIP-1β was
almost 3 folds above the reference limits. The IL-2, IL-6, were 2.3 times the normal upper reference limit before
and TNF-α levels of patient G were within the normal treatment, and after treatment with RepG3, the level of
range (Figure 1). RANTES/CCL5 increased by +13%, up to 26,973 pg/mL
In contrast, the after-treatment blood results revealed (Figure 2).
that 10 days of 2 mg/day ezrin peptide RepG3 normalized These anecdotal results from patient-G stimulated
his elevated proinflammatory cytokines below the reference an investigation of the literature on the expression and
limits for IL-4, IL-6, IL-8, IL-13, and GM-CSF (IL-1β was
not assessed). Some of the reductions were remarkable: biological activities of RANTES/CCL5 because the
cytokine IL-13 decreased from 84 pg/mL to 4 pg/mL above data suggested that ezrin peptides stimulated
and chemokine MIP-1α decreased from 113 to 2 pg/mL. RANTES/CCL5 expression. After ezrin peptide HEP1
As expected, IL-2 remained in the healthy range and was (TEKKRRETEREKE) was registered for human use in
not affected by RepG3. The anti-inflammatory regulatory Russia in 2001, over 25 clinical trials demonstrated the
cytokine (IL-10) was also reduced to normal levels. Ezrin immune amplification and anti-inflammatory activity
peptide RepG3 reduced proinflammatory cytokines, in of ezrin peptide HEP1, but this new data suggested that
line with in vitro experiments with ezrin peptide-treated the ezrin peptide immune amplification effect could be
PHA-stimulated human PBMC and in vivo treatment of mediated by RANTES/CCL5. 18
DSS-inflamed mice. In general, patient G felt better after
18
RepG3 treatment. 3. Immune amplifier RANTES/CCL5 and
control of infection
Ezrin peptide RepG3 also reduced and normalized the
serum levels of the proinflammatory chemokine MIP-1α RANTES, meaning “regulated on activation, normal
and MIP-1β, which are closely related to the chemokine T-cell expressed and secreted,” was originally considered
RANTES/CCL5. However, his RANTES/CCL5 levels a T lymphocyte-specific chemokine supporting the growth

Volume 1 Issue 1 (2024) 3 doi: 10.36922/mi.2474