Wednesday, July 25, 2018

Cure your flu and melanoma too???


Interesting.... 

The clinically approved MEK inhibitor Trametinib efficiently blocks influenza A virus propagation and cytokine expression.  Schrader, Dudek, Schreiber, et al.  Antiviral Res. 2018 Jul 7.

Influenza A virus (IAV) infections are still a major global threat for humans, especially for the risk groups of young children and the elderly. Annual epidemics and sporadically occurring pandemics highlight the necessity of effective antivirals that can limit viral replication. The currently licensed antiviral drugs target viral factors and are prone to provoke viral resistance. In infected host cells IAV induces various cellular signaling cascades. The Raf/MEK/ERK signaling cascade is indispensable for IAV replication because it triggers the nuclear export of newly assembled viral ribonucleoproteins (vRNPs). Inhibition of this cascade limits viral replication. Thus, next to their potential in anti-tumor therapy, inhibitors targeting the Raf/MEK/ERK signaling cascade came into focus as potential antiviral drugs. The first licensed MEK inhibitor Trametinib (GSK-1120212) is used for treatment of malignant melanoma, being highly selective and having a promising side effect profile. Since Trametinib may be qualified for a repurposing approach that would significantly shorten development time for an anti-flu use, we evaluated its antiviral potency and mode of action. In this study, we describe that Trametinib efficiently blocks replication of different IAV subtypes in vitro and in vivo. The broad antiviral activity against various IAV strains was due to its ability to interfere with export of progeny vRNPs from the nucleus. The compound also limited hyper-expression of several cytokines. Thus, we show for the first time that a clinically approved MEK inhibitor acts as a potent anti-influenza agent.

I have ranted to kids and families for years about the importance of avoiding flu through good health care techniques and the flu vaccine!  Looking at data from the CDC from the late 70's through 2007 ~ 3,000 to 49,000 folks died from flu ANNUALLY, depending on the season, just in the United States!!  This study notes that in order for the flu A virus to replicate in our bodies, it requires the RAF/MEK/ERK signaling cascade.

Remember this diagram???  Anyhow, in this report researchers found that in little mice and the petri dish, Trametinib, the first FDA approved MEK inhibitor that we use in melanoma, blocked the replication of some types of flu A!   MEK inhibitors do come with some pretty gnarly side effects, at least for some, so I'm not sure it would be recommended for everyone, but maybe it would be a possibility for high risk folks.  We also have to remember that illness due to flu B makes up a huge part of flu cases as well.  The more important intel from this study may be noting once again how creepily similar cancer and viruses can be!  Thereby, holding out hope that one day, an effective vaccine may be developed for melanoma!!! 

For what it's worth! - c

1 comment:

  1. Interesting, I wonder getting a flu shot effects those of us taking Trametinib, Mekinist?

    ReplyDelete