2.3 Anti-viral properties of furosemide
Besides its anti-inflammatory properties and positive effects in dyspnoea, furosemide has also been shown to exhibit anti-viral properties. Voss et al. (1996) concluded that furosemide inhibited the Na+/K+/2Cl-cotransporter and thereby blocked the cytopathic effects of alterations in intracellular cation concentration induced by the human immunodeficiency virus (HIV), a single-stranded, positive-sense, enveloped RNA virus member of the genus Lentivirus , part of the family Retroviridae . In cells infected with a cytopathic strain of HIV-1, the activity of the Na+/K+/2Cl-cotransporter was significantly increased, leading to a higher Na+ and K+ concentrations and thereby to an increased cell volume. This pathological swelling can then lead to membrane disruption and ultimately cell death. Inhibition of the Na+/K+/2Cl-cotransporter by furosemide, however, was able to reduce this pathological process, prolonging the survival of cells by 2-4 weeks.
Ulug et al. (1989) studied the influence of cation gradients in the release of Sindbis virus, a positive-sense, single-stranded RNA virus, from infected cells. The cell volume of Sindbis virus infected cells is reduced and the activity of the Na+/K+ ATPase is decreased, presumably to maintain a higher, intracellular concentration of monovalent cations. Especially in low salt media, but also, with reduced extent, in isotonic media, the treatment of infected cells with furosemide inhibited the release of Sindbis virus from these cells through the inhibition of the Na+/K+/2Cl-cotransporter. In another study by Hartley et al. (2006), the effect of furosemide-induced inhibition of the Na+/K+/2Cl-cotransporter in DNA and RNA viruses was explored. According to these authors, DNA viruses are dependent upon K+ for replication, thus stopping K+ influx by inhibition of the Na+/K+/2Cl-cotransporter would have broad-spectrum anti-viral effects. While reduced replication was indeed observed for DNA viruses, the replication of the RNA virus was not inhibited. These multiple studies all conclude that the pathologic alteration of intracellular cation concentrations mediated by viral action can be blocked by furosemide through inhibition of the Na+/K+/2Cl-cotransporter.
Finally, it is important to note that furosemide’s anti-viral activities do not require systemic administration of the drug. Indeed, topical and locally administered furosemide gel has demonstrated efficacy against warts caused by the human papillomavirus.