Inosine pranobex (BAN; also known as inosine acedoben dimepranol (INN), methisoprinol, inosiplex or Isoprinosine) is an antiviral drug that is a combination of inosine and dimepranol acedoben (a salt of acetamidobenzoic acid and dimethylaminoisopropanol) in a ratio of 1 to 3. It is used primarily in European countries, especially as a treatment for acute viral infections, such as the common cold.
Mechanism of action
Immunomodulatory effects Inosine pranobex acts as an immunostimulant, an analog of thymus hormones. It is indicated for an entire spectrum of patients with clinical manifestations of immune deficiency. It modulates the immune system by immunostimulation or immunooptimisation of defensive inflammation at the cellular level, e.g. by interfering with energy metabolism, cell signalling and proliferation. One of the main immunostimulatory effects of inosine pranobex lies in T-cell modulation. Its administration has been shown both in vivo and in vitro to induce Th1 cell-type response, as evidenced by the increase in pro-inflammatory cytokines (e.g. IL-2, ILN-γ) in mitogen- or antigen-activated cells. As such, T-cell maturation and differentiation is further fostered. The increase of ILN-γ in serum is proven to inhibit the production of IL-10, which could explain the drug's suppressive effect on anti-inflammatory cytokines. It also modulates components of innate immunity. In respect to natural killer cells, both population and activity increased as a result of inosine pranobex therapy. It has also been proven that other cells of the innate immunity are affected, as neutrophil, monocyte and macrophage chemotaxis and phagocytosis were enhanced in cancer patients.
Antiviral properties Inosine pranobex also has direct antiviral properties. Several hypotheses have been formed over time, but all of them agree that the drug has direct effect on viral RNA synthesis via inhibiting transcription and translation of the genetic code at cellular level. In fact, cellular RNA and protein synthesis are markedly depressed shortly after viral infection, as the cell is instructed to focus resources on producing viral RNA instead. Inosine pranobex is believed to override this mechanism and incentivize cellular RNA synthesis over viral. It has been suggested that the drug itself, or any one of its components, directly acts on the ribosomes of infected cells providing an advantage to cellular RNA in competition for synthesis. This could also result in errors in the viral RNA transcription, which would hinder viral proliferation as well. Another hypothesis suggests that inosine itself has direct antiviral properties, as evidenced by the rather fast metabolism of the compound.It is assumed that the drug breaks down metabolically into its constituents, therefore permitting direct inosine action. Inosine is proven to act on ribosome directly, as such one theory suggests that it inhibits the synthesis of phosphoribosyl pyrophosphate from ribose phosphate, the former being an intermediate in the biosynthesis of purine nucleotides such as adenylate and guanylate. A 2014 study has also shown that inosine affects DNA and RNA directly, as such the wobble mechanism, in which inosine replaces adenine, might result in errors in viral RNA furthermore. It is apparent that inosine pranobex acts on the viral replication through many mechanisms, and is as such pleiotropic in nature. Most of these mechanisms are not specific to certain viruses and as such the drug is potent in treating a wide spectrum of viral infections, something that is rather uncommon for antivirals, as they tend to be very specific in their target. These mechanisms are also so general that no virus has been ever shown to develop resistance to them. Macroscopically, antiviral activity has been documented in vivo on several animal models, and experimentally tested on the cytomegalovirus and influenza disease strains. In vitro, there is antiviral activity documented for many RNA and DNA viruses including, but not limited to: herpes simplex virus, cytomegalovirus, adenovirus, poliovirus, and influenza A and B viruses.
Clinical applications
Preventative use For patients with sub-optimally functioning immune systems, inosine pranobex can also be helpful in managing and decreasing the incidence of common viral infections, such as the common cold or influenza. As such, it is commonly prescribed preventatively, albeit at a lower dose. Several studies have investigated the benefits of inosine pranobex therapy in frequently ill children and returned positive results in both clinical and immunological outcomes.
Herpesvirus infections Inosine pranobex has been suggested as an antiviral for herpesviruses, such as herpes simplex virus types 1 and 2, cytomegalovirus (CMV), and Epstein-Barr virus (EBV), The drug also proved helpful in managing complicated cases of lengthy reactivations of herpesviruses such as EBV, and subsequent post-viral fatigue.
Human papilloma virus (HPV) infections Inosine pranobex may be prescribed for the treatment of HPV infections both benign and oncogenic, as a very safe and effective alternative therapy. Usually it is administered in combination with other treatment methods, such as CO2 laser and podophyllotoxin. It was proven to be effective at treating genital warts in combination with conventional non-surgical treatments. It can also be used to treat vulvar HPV infection, and cervical dysplasia. It was also suggested as a possible alternative treatment for young women with chronic vulvodynia. Several long-term studies have shown efficacy even compared to surgical method at treating oral HPV-positive proliferative verrucous leucoplakia (PVL).
Influenza and rhinovirus infections The evidence in treating rhinovirus infections is mixed. While no statistically significant effect was observed in rhinovirus 44 or 32 infection, its administration in rhinovirus 21 infection led to statistically improved health outcomes in patients, shortened infectivity and decreased viral shedding. In Influenza and Influenza-like (RSV, adenovirus and parainfluenza virus) infections, inosine pranobex did lower the symptom severity and duration.
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