5. DISCUSSION
The novel SARS-CoV-2 infection is straining global health systems. The massive spread of the virus is requiring new response paradigms from the scientific community. The first step of the pharmacological strategy was to consider molecules already on the market for a reasoned use in the treatment of viral pneumonia COVID-19 (Li and De Clercq, 2020). As a consequence, most of the antiviral drugs currently registered in clinical trials are medicines with other indications, but which can potentially benefit patients affected by COVID-19.
Based on clinical experience from SARS and MERS, and considering the characteristic of this single-stranded RNA beta-coronavirus, a number of antiviral nucleoside analogue drugs, such as favilavir, which selectively inhibits viral RNA-dependent RNA polymerase, or ritonavir, a protease inhibitor used against the hepatitis C virus, are currently in trials. Other specific antiviral drugs are being analysed in order to find a specific pharmacological response to this pandemic (Li and de Clercq, 2020).
Alongside this approach, some non-specific pharmacological strategies with secondary mechanisms of action against the virus have been considered, such as the immune modulator chloroquine (Touret and de Lamballerie, 2020). This strategy has shown promising in vivo andin vitro data and some clinical evidence, the latest reported by Gao et al. (2020) describing the superiority of chloroquine over the control group in a Chinese clinical trial. Now, a number of clinical trials are starting in order to best delineate these first evidence (Touret and de Lamballerie, 2020). Others non-specific pharmacological approaches are currently under investigation including the use of inhaled medicines (table 1). For example, nitric oxide gas is a selective pulmonary vasodilator administered to COVID-19 patients as a rescue therapy for refractory hypoxemia due to acute respiratory distress syndrome (ARDS). Some evidence from in vitro and clinical data have pointed out that inhaled nitric oxide gas (iNO) has exerted nonspecific antiviral activity (ClinicalTrial.gov id: NCT04290871).
Here, the possibility of a nonspecific pharmacological effect focused on the pulmonary site of action has been discussed. In addition to pharmaceutical aerosols targeting drugs to the lower respiratory tract, here the possibility of exploiting the pulmonary elimination mechanism to concentrate molecules with non-specific action in the lungs is considered (fig. 3). The limitations of this strategy are defined by the particular characteristics that the candidate molecules must possess; on the other hand, the pulmonary elimination process favours a local concentration of the xenobiotic, which consequently can better reach a dose-dependent pharmacological effect. This peculiar pharmacokinetic aspect linked to the characteristics of a non-specific antiviral molecule may provide a therapeutic advantage to reach and treat this aggressive viral pneumonia.