Naproxen shows anti-viral activity against flu

Pain reliever shows anti-viral activity against flu — ScienceDaily Mar 2013Source: American Society for Microbiology

This was a total surprise to me and, considering the specter of a new coronavirus spreading across the globe, I thought this information could be very useful.

New influenza vaccines must be developed annually, because the surface proteins they target mutate rapidly. The researchers found a much more stable, reliable target for anti-influenza activity.

The so-called ribonucleoprotein complexes are necessary for replication, and the researchers realized they could target the nucleoprotein, preventing assembly of the complexes. Because of its vital function, the nucleoprotein is highly conserved, making it a good potential target for antiviral drugs.  

Naproxen protected Madin-Darby canine kidney (MDCK) cells against viral challenges with the H1N1 and H3N2 viral strains and was much more effective than other cyclooxygenase inhibitors in decreasing viral titers of MDCK cells

The nucleoprotein’s three dimensional structure, solved in 2006, provided the basis for searching for new drugs that could interfere with its action.

The researchers did a virtual screening within the Sigma-Aldrich online catalog of biochemicals. That screening identified Naproxen, better known as the over-the-counter pain reliever Aleve, and as expected, it bound to the nucleoprotein, and impeded RNA binding.

In further testing, it reduced the viral load in cells infected with H1N1 and H3N2 influenza A virus, and in mice it demonstrated a therapeutic index against influenza A that was superior to that of any other anti-inflammatory drug.

Specifically, naproxen

  • blocks the RNA binding groove of the nucleoprotein,
  • preventing formation of the ribonucleoprotein complex,
  • thus taking the vital nucleoproteins out of circulation

As an already approved drug, naproxen could become a treatment against influenza relatively quickly, the researchers write. Its status as a non-steroidal anti-inflammatory drug (NSAID), which inhibits the COX-2 pathway, as well as an antiviral would boost its efficacy.

Below is the study referenced for the article above:

Structure-Based Discovery of the Novel Antiviral Properties of Naproxen against the Nucleoprotein of Influenza A Virus | Antimicrobial Agents and Chemotherapy – Mar 2013

We report here that monomeric nucleoprotein can be inhibited by a small molecule binding in its RNA binding groove, resulting in a novel antiviral against influenza A virus.

In a mouse model of intranasal infection, naproxen treatment decreased the viral titers in mice lungs.

DISCUSSION

Naproxen binds to the targeted site in the RNA groove of NP.

In this work, we aimed at inhibiting the binding of the nucleoprotein to RNA for interference with NP function. To achieve this goal, part of the RNA binding groove was blocked by naproxen, a compound identified by virtual screening which binds within the RNA binding groove of the nucleoprotein.

Direct evidence for naproxen binding to the nucleoprotein was given by the specific signal of the naproxen-NP complex using NP attached to the surface. SPR also showed that naproxen binding to NP was competitive with RNA and disrupted the RNA-NP complex.

Antiviral and anti-inflammatory effects of naproxen in IAV-infected cells.

Cyclooxygenase type 2 (COX-2) is a component of the arachidonic acid cascade thought to be involved in inflammatory and immune responses; naproxen is a COX-2 inhibitor used to treat these symptoms in humans.

Influenza A viruses induce high levels of proinflammatory cytokines in macrophages and alveolar epithelial cells, and COX-2 plays a regulatory role in induction of H5N1-mediated proinflammatory responses in vitro.

Such cytokine deregulation was proposed to be a major contributor to the pathogenesis of H5N1 disease in humans.

the naproxen antiviral effect was significantly more potent than those of nimesulide and the other COX-2 selective inhibitors tested.

our results are potentially very significant on the basis of the following considerations.

  • Naproxen constitutes a lead compound to be improved by drug design; its main binding site is known and was shown by the use of site-directed mutants. Docking experiments identified residues involved in additional binding modes of naproxen.
  • Naproxen is equally effective against the viral variants H1N1 and H3N2.
  • Importantly, we demonstrated that blockade of the RNA binding groove of NP in its monomeric form results in antiviral effects, presumably through sequestration of active NP monomers. 

In conclusion, in the era of dual pharmacology, where the efficacy of a drug is improved by reaching more than one target while being nontoxic, naproxen has the advantage of inhibiting both COX-2 and the nucleoprotein of influenza A virus.

Naproxen is more potent than COX-2 inhibitors such as nemesulide against influenza A virus challenge.

Importantly, naproxen is a safe, potential pharmaceutical readily available for cases of resistance to antiviral and if an IAV infection pandemic emerges.


After reading this, I searched the NIH National Library of Medicine for further research and found surprisingly few studies pursuing this promising lead. However, I found a few more studies that back up these findings from 2015, 2018, and the most recent from 2019.

Naproxen Exhibits Broad Anti-influenza Virus Activity in Mice by Impeding Viral Nucleoprotein Nuclear Export. – PubMed – NCBI May 2019 

Naproxen is a non-steroidal anti-inflammatory drug that has previously been shown to exert antiviral activity against influenza A virus by inhibiting nucleoprotein (NP) binding to RNA. Here, we show that naproxen is a potential broad, multi-mechanistic anti-influenza virus therapeutic, as it inhibits influenza B virus replication both in vivo and in vitro.

This study reveals a crucial mechanism of broad-spectrum anti-influenza virus activity of naproxen, suggesting that the existing drug naproxen may be used as an anti-influenza drug.

From Naproxen Repurposing to Naproxen Analogues and Their Antiviral Activity against Influenza A Virus. – PubMed – NCBI Aug 2018 

The nucleoprotein (NP) of influenza A virus (IAV) required for IAV replication is a promising target for new antivirals. We previously identified by in silico screening naproxen being a dual inhibitor of NP and cyclooxygenase COX2, thus combining antiviral and anti-inflammatory effects.

Here we designed and synthesized two new series of naproxen analogues called derivatives 2, 3, and 4 targeting highly conserved residues of the RNA binding groove, stabilizing NP monomer without inhibiting COX2

Structure-based design of novel naproxen derivatives targeting monomeric nucleoprotein of Influenza A virus – free full-text /PMC4548311/Sep 2015

We recently identified naproxen as a drug competing with RNA binding to NP with antiinflammatory and antiviral effects against influenza A virus.

Here, we designed novel derivatives of naproxen by fragment extension for improved binding to NP.

Naproxen C0 is a potential antiviral candidate blocking influenza nucleoprotein function.

 

5 thoughts on “Naproxen shows anti-viral activity against flu

  1. Kathy C

    Naproxin may have some effect on the flu, but there are a lot of people on it, and there has been no visible effect. This is anecdotal, but I know several people who take daily doses of naproxin, and still got the flu this year. These bit of research are interesting, but there is so much misinformation going around about the flu and the corona virus. A lot things kill or block viruses in a lab or in a certain species, but have no effect in a population. Perhaps the mechanism involved could be studied,and lead to a new drug, but in the meantime a lot of this is industry funded and dangerous.

    Liked by 1 person

    Reply
    1. Zyp Czyk Post author

      I was suspicious too, so I did a search on PubMed and found this:

      Best matches for “naproxen antiviral”:

      From Naproxen Repurposing to Naproxen Analogues and Their Antiviral Activity against Influenza A Virus.
      Dilly S et al. J Med Chem. (2018)
      https://www.ncbi.nlm.nih.gov/pubmed/30028133

      Naproxen Exhibits Broad Anti-influenza Virus Activity in Mice by Impeding Viral Nucleoprotein Nuclear Export.
      Zheng W et al. Cell Rep. (2019)
      https://www.ncbi.nlm.nih.gov/pubmed/31067470

      Novel Antiviral Properties of Naproxen against the Nucleoprotein of Influenza A Virus (2018)
      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3632891/

      But you’re right, a new drug based on this newly-discovered mechanism is what’s needed.

      Also, while naproxen certainly does not and cannot *prevent* the flu, it can reduce the viral load. (I know 2 people who got the flu right after getting the vaccination – it hadn’t taken effect yet) The people who got the flu while taking naproxen may have suffered worse symptoms if they weren’t taking it.

      With all the lies and propaganda about health issues these days and the sole focus on profits, it’s hard to find the few nuggets of truth. I try not to post things that are only media-hype without pointing them out to be exactly that, so if you find such a post, please let me know.

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      Reply
  2. Kathy C

    I am skeptical of Chinese research and most of the industry funded advertised “research” going on. There are all sorts of marketers attempting to cash in on the Corona Virus. The stock hyping shows, are promoting stocks that might go up, if we have a pandemic. Even on NPR, they were talking about the corporation making the face masks as a good investment. Their stock went up, as stores sold out of face masks. It is ghoulish, cashing in on the death and despair. They did the same thing with opiates, back in 2012, they were hyping treatment centers as a good investment, while peddling “choice’ and faith based abstinence programs.

    We live in dangerous times, when one deceptive lie can go “viral” and get regurgitated across all media.

    Liked by 1 person

    Reply

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