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Microbes & Immunity

REVIEW ARTICLE
The therapeutic potential of RANTES/CCL5

across diverse infections and its synergistic
enhancement by ezrin peptide RepG3 for long

COVID

Rupert Holms*
Newal R&D Ltd., London, United Kingdom

Abstract
The amplification of anti-infective immunity against a wide spectrum of acute
and chronic infections caused by various pathogens is mediated by RANTES/
CCL5. This chemokine controls infections caused by viruses, bacteria, fungi, and
protozoans. In addition, RANTES/CCL5 exhibits anti-cancer effects by increasing
NK-cell activity and targeting tumors. RANTES/CCL5 acts by amplifying antigen-
specific immunity on mucosal surfaces, programmed T-cell responses, cytotoxic
T lymphocytes (CTL), B-cell activation, and antibody production. RANTES/CCL5
exerts its effects by binding to C-C receptors, thereby triggering JAK/STAT
signaling and inducing the migration of lymphocytes, NK cells, and monocytes. In
*Corresponding author: the brain, RANTES/CCL5 activates astrocytes and upregulates anti-inflammatory
Rupert Holms interleukin (IL)-10 expression. Inflammatory cytokines rapidly induce RANTES/
(rupertholms@newalrnd.com) CCL5 expression in fibroblasts, epithelial cells, and monocytes/macrophages.
Citation: Holms R. The therapeutic In T-cells, RANTES/CCL5 expression is mediated by translational control of the
potential of RANTES/CCL5 across transcription factor RFLAT-1/KLF13, which is responsible for a 3-day delay in
diverse infections and its synergistic
enhancement by ezrin peptide RANTES/CCL5 secretion after T-cell activation. A cell membrane multi-protein
RepG3 for long COVID. Microbes & complex containing CFTR, EBP50, ezrin, and PKC is a dominant regulator of both
Immunity. 2024;1(1):2474. RANTES/CCL5 and inflammatory cytokine expression. Treatment of a volunteer
doi: 10.36922/mi.2474 patient suffering from long COVID/vaccine injury with the ezrin peptide RepG3
Received: December 19, 2023 alleviated symptoms, substantially reduced serum proinflammatory cytokines
Accepted: February 4, 2024 to normal levels, and enhanced the expression of RANTES/CCL5. The immune
amplification activities of RANTES/CCL5 and the ezrin peptide RepG3 exhibit
Published Online: March 6, 2024 striking similarities. In contrast, the ezrin peptide RepG3 differs from RANTES/
Copyright: © 2024 Author(s). CCL5 in its ability to significantly inhibit the expression of proinflammatory
This is an Open-Access article cytokines IL-1β, IL-6, IL-8, IL-13, TNF-α, and proinflammatory chemokines MIP-1α
distributed under the terms of the
Creative Commons Attribution and MIP-1β. The mechanism through which the ezrin peptide RepG3 enhances
License, permitting distribution, adaptive immunity likely involves its induction of systemic elevation of RANTES/
and reproduction in any medium, CCL5 expression and the simultaneous inhibition of proinflammatory cytokine
provided the original work is
properly cited. expression.
Publisher’s Note: AccScience
Publishing remains neutral with Keywords: RANTES; CCL5; CCR5; Ezrin peptide; Immune amplification; Anti-
regard to jurisdictional claims in
published maps and institutional inflammatory; SARS-CoV-2; Long COVID
affiliations.

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