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.