1. Introduction
Coronaviruses are a group of single-stranded RNA viruses that are
characterized by a spherical shape, which provides them the typical
”crown” appearance. These viruses, which were first identified in the
mid-1960s, can be categorized into four subfamilies:
α−/β−/γ−/δ-Coronavirus. Gamma and delta-coronaviruses are more inclined
to infect birds, while alpha and beta-coronaviruses mainly infect
mammals [1 ]. Specifically, β−coronaviruses include the
Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and the Middle
East Respiratory Syndrome Coronavirus (MERS-CoV), detected in Guangdong
in 2002 and in Saudi Arabia in 2012, respectively. On December 2019, a
novel β−Coronavirus, SARS-CoV-2 (Severe Acute Respiratory Syndrome
Coronavirus 2 ), has emerged in Wuhan (Hubei province, China) where it
was found to be responsible of the new COVID-19 [2 ]. After
a rapid spread worldwide of the disease, the World Health Organization
(WHO) announced COVID-19 outbreak a pandemic. According to current
evidence, the epidemic started with animal to human transmission
[3 ]. A phylogenetic analysis has demonstrated that the new
coronavirus significantly clustered with the sequence of bat SARS-like
coronavirus [3 ]. It has envelopes, and the particles are
round or oval with diameter from 60 to 140 nm [4 ]. As for
other coronaviruses, the replication of SARS-CoV-2 starts with the
attachment to the host cell through interactions between the Spike
protein (S protein) and its receptor. In this phase, the virus interacts
with ACE2 receptor and the serine protease TMPRSS2. Once into the cell,
replication and transcription phases start [5,6 ].
The transmission among people occurs through respiratory droplets ad the
incubation time ranges from 3 days to 2 weeks [7 ]. In mild
cases SARS-Cov-2 infection can occur with fever, fatigue and dry cough,
while severe cases frequently occur with pneumonia, respiratory and
kidney failure. Apart from respiratory and flu-like symptoms, this
infection may be complicated by lymphopenia and interstitial pneumonia
with high levels of pro-inflammatory cytokines, such as IL-1, IL-2,
IL-6, G-CSF, IP-10, and TNFα. This condition leads to the so-called
”cytokine storm” which, in turn, can induce acute respiratory distress
syndrome (ARDS), organ failure, sepsis, potentially progressing to
patient’s death [8 ]. Patients with mild form of COVID-19
shall be eligible for isolation and, sometimes, symptomatic treatments
(mainly paracetamol for fever control). On the other hand, patients
presenting severe pneumonia require hospitalizations and frequently the
access to intensive care units where mechanical ventilation can be
provided. For these patients pharmacological treatments is strongly
needed. Nowadays, no specific drug therapies neither vaccines are
available for the treatment of COVID-19. Since there is no time to
evaluate new drug therapies, drug repositioning may offer a strategy to
efficiently control clinical course of the disease and the spread of
pandemic [9 ].
In this paper we aim to provide an overview of treatments currently
administered in patients with COVID-19, mainly focusing on antivirals
and drugs with immune-modulatory and/or anti-inflammatory properties,
their pharmacological features and achievement in term of patients’
clinical outcomes. A close examination of drugs that are currently under
clinical development is provided as well. The mechanism of action, main
safety concerns and drug-drug interactions of antiviral,
immune-modulatory and anti-inflammatory agents currently used or under
clinical development for the treatment of COVID-19 are reported in table
1.