AG5 is a potent non-steroidal anti-inflammatory and immune regulator that preserves innate immunity.

An archetypal anti-inflammatory compound against cytokine storm would inhibit it without suppressing the innate immune response. AG5, an anti-inflammatory compound, has been developed as synthetic derivative of andrographolide, which is highly absorbable and presents low toxicity. We found that the mechanism of action of AG5 is through the inhibition of caspase-1. Interestingly, we show with in vitro generated human monocyte derived dendritic cells that AG5 preserves innate immune response. AG5 minimizes inflammatory response in a mouse model of lipopolysaccharide (LPS)-induced lung injury and exhibits in vivo anti-inflammatory efficacy in the SARS-CoV-2-infected mouse model. AG5 opens up a new class of anti-inflammatories, since contrary to NSAIDs, AG5 is able to inhibit the cytokine storm, like dexamethasone, but, unlike corticosteroids, preserves adequately the innate immunity. This is critical at the early stages of any naïve infection, but particularly in SARS-CoV-2 infections. Furthermore, AG5 showed interesting antiviral activity against SARS-CoV-2 in humanized mice.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: “AG5 andrographolide derivative for use in the treatment of inflammatory diseases associated with a cytokine storm” is a formal Spanish Patent (ES2908500) since March 15th, 2023. PBA, ERB, CVA, BN, AF, CS, GGA, FP, JA, APL and JMB are co-inventors of this patent.
(Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)