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.