PREreview of Tretinoin, a Vitamin A derivative, exerts antiviral effects against Chikungunya virus infection through the nuclear retinoid receptor signaling pathways

This preprint explores the antiviral effects of tretinoin, a Vitamin A derivative, against Chikungunya, which currently lacks antiviral treatments. Tretnoin acts as a ligand for retinoic acid receptors (RARs), which regulate gene expression related to cell growth and immune responses. While chikungunya is not new, it has been showing a global reemergence recently, and thus, the paper is quite timely. 

Some major issues that struck me as odd included the ambiguity of the proper peer reviewer. This paper covers a lot of methods, from RT-qPCR to in vivo titer tests. Most peer reviewers will not have expertise in all the methods, since they cover a broad range, but it’s good that the data is being validated in different forms.

Tretinoin is typically administered topically or at low dosages because of its potential toxicity. If the observed antiviral activity occurs outside of the recommended concentrations, the clinical translation of tretinoin might be limited. The main in vivo data were derived from CHIKV-infected mice, not humans. The way in which the immune and metabolic systems in mice respond to the drug is different from that of humans, so the results might not translate exactly to human outcomes.  Tretinoin, as a retinoid, can induce side effects, including cytotoxicity, oxidative stress, and immune modulation, which suppresses pro-inflammatory cytokines and can impair the host’s own mechanisms for clearing the infection. There is limited evidence regarding the ex vivo human-derived macrophage assays, as only one immune cell population type was evaluated, without comparing responses amongst other CHIKV target cells like T cells, dendritic cells, and endothelial cells.

Competing interests

The author declares that they have no competing interests.

Use of Artificial Intelligence (AI)

The author declares that they used generative AI to come up with new ideas for their review.