Onychomycosis is a therapeutically challenging fungal infection. Systemic antifungals are limited by adverse effects and drug interactions, while topical therapies may fail to achieve therapeutic nail bed concentrations. Nitric oxide (NO), a small, diffusible free radical with broad-spectrum antimicrobial activity, offers a novel approach to overcoming these barriers. We assessed the penetration and subsequent efficacy of a nitric oxide–releasing gel (NORG) in the treatment of onychomycosis. Ex vivo human nail models assessed NORG’s transungual penetration and antifungal activity via colorimetric, immunohistochemical, and microbiological assays. NORG eradicated Trichophyton mentagrophytes completely (0 CFU/g), outperforming terbinafine (3.58 ± 0.2 log₁₀ CFU/g). In an ex vivo infection model, NORG achieved fungal clearance within 14 days, continuing to Day 30 treatment end, with no regrowth during 21 days of incubation post-treatment. Clinical data from patients with onychomycosis who received topical NORG therapy show that NORG penetrated the nail plate and nail bed, as evidenced by s-nitrosothiol accumulation and progressive discoloration. The NORG formulation demonstrates in vitro efficacy; controlled trials are warranted to fully assess clinical efficacy and safety of this NORG formulation in humans, and establish optimal treatment protocols.

Respiratory viruses such as SARS-CoV-2, influenzas A and B, respiratory syncytial virus (RSV), human metapneumovirus (hMPV), human parainfluenza virus type 3 (HPIV-3), and rhinoviruses remain major causes of global morbidity. Their rapid evolution, high transmissibility, and limited therapeutic options, together with the absence of approved vaccines for several pathogens, highlight the need for broad-acting and pathogen-independent antiviral strategies. Nitric oxide exhibits antiviral activity through redox-dependent mechanisms, including S-nitrosylation of cysteine-containing viral proteins and disruption of redox-sensitive structural domains. Clinical studies conducted during the SARS-CoV-2 pandemic demonstrated that a nitric oxide nasal spray (NONS) rapidly reduced nasal viral load and transmission. In this study, we evaluated the in vitro virucidal activity of the NONS against a panel of clinically relevant respiratory viruses representing four major virus families. Virus suspensions of approximately 10⁴ CCID₅₀ were exposed to a full-strength NONS for contact times ranging from 5 s to 2 min at room temperature, followed by neutralization and quantification of residual infectivity using endpoint dilution assays. The NONS rapidly reduced viral infectivity across all viruses tested, achieving >3 log₁₀ reductions within 2 min. SARS-CoV-2 variants including Alpha, Beta, Gamma, Delta, Omicron BA.1, and XBB 2.0 were reduced to levels at or below the assay detection limit within 30 s to 2 min. Influenza A and B viruses showed the fastest loss of infectivity, reaching detection limits within 10–15 s. RSV, hMPV, HPIV-3, and human rhinovirus 14 were similarly inactivated within 1–2 min. These findings demonstrate that the NONS exhibits rapid and broad-spectrum virucidal activity against diverse respiratory viruses and supports its potential role in pandemic preparedness but also seasonal use.

A commercially available nitric oxide (NO)-releasing solution (NORS) has demonstrated in vitro efficacy for dermatophytosis, but a NO-releasing gel (NORG) may be more suitable for patient self-application. We present a preliminary investigation of NORS for tinea pedis and an in vitro investigation of NORG for dermatophyte infection, to complement the existing published data and expand support for a possible role of NO formulations in superficial dermatophyte infection. In vitro usage of NORS and NORG is reviewed. The antifungal efficacy of NORG was assessed via time-kill assays, zone of inhibition tests with synthetic dermal membrane permeation, and scanning electron microscopy. A randomized, controlled pilot study of NORS for tinea pedis investigated the safety and efficacy of treatment over three consecutive days, with a day-31 follow-up. The NORG demonstrated rapid fungicidal activity against T. rubrum and T. mentagrophytes and effective dermal membrane penetration while retaining antifungal action. Significant morphological damage to fungal cells was noted, indicating possible fungicidal activity. The clinical NORS treatment reduced the clinical symptom severity score by 67% on average, with no significant safety findings. These findings, in addition to existing publications, support NO-releasing formulations as potential therapies that warrant further clinical investigation for superficial fungal infection.