Ivermectin thwarts aswell viral replication via its binding to RNA-dependent RNA polymerase (RdRp) [61]. The anti-inflammatory properties of ivermectin has been also documented. from adult studies. No randomized controlled trials (RCTs) including pediatric COVID-19 patients have assessed these medications efficacy and safety, among others. Similarly, three novel monoclonal anti-SARS-CoV-2 spike protein antibodies, bamlanivimab, casirivimab and imdevimab, have been recently authorized by the USFDA. Nonetheless, their efficacy has not been exhibited by multiple RCTs. In this review, we aim to dissect the various potential therapeutics used in children with COVID-19. We aspire to provide a comprehensive review of the available evidence and display the mechanisms of action and the pharmacokinetic properties of the analyzed therapeutics. Our evaluate offers an efficient and practical lead for treating children with COVID-19. [36]Their clinical uses are derived from their anti-inflammatory, immunomodulatory, and antimicrobial properties. CQ/HCQ inhibits viral access and intracellular replication (observe Fig.?1). They exert their antiviral effects via (1) the inhibition of sialic acid synthesis, (2) the binding to sialic acid and gangliosides, (3) the impairment of viral cellular conversation, and (4) the interference with intracellular pathways that are key for viral replications such as p38 mitogen-activated protein kinase (MAPK) pathway [36]. Similarly, they boost the dendritic cells activity which, in turn, enhances the activity of cytotoxic T cells. They are known to attenuate the inflammatory response mounted against pathogens and autoimmune triggers. This effect is usually achieved via the downregulation of the release of pro-inflammatory cytokines (such as Il1-, TNF-, and Il6) that can result in hyperinflammation and tissue destruction [36]. Open in a separate windows Fig. 1 The potential therapeutics of COVID-19 and their suggested mechanisms of action. Chloroquine/hydroxychloroquine (CQ/HCQ) is known for its anti-inflammatory and antimicrobial effects. They inhibit viral fusion, endocytosis, and intracellular replication. Similarly, they modulate the inflammatory response mounted against the computer virus by attenuating the excessive uncontrolled release of pro-inflammatory cytokines. Oseltamivir is usually a selective inhibitor of the neuraminidase enzymes of the influenza computer CXCL12 virus. These enzymes are involved in various viral processes including viral access, replication, packaging, and release. Hence, their use in SARS-CoV-2 contamination may thwart the cellular processing of this computer virus at different levels. Remdesivir is usually a potent inhibitor of viral replication. It exerts its effect through the selective inhibition of the RNA-dependent RNA polymerase. Remdesivir, unlike CQ/HCQ, oseltamivir, and ivermectin, is usually a direct inhibitor of RNA-dependent RNA polymerase. CQ/HCQ, oseltamivir, and ivermectin hinder indirectly the replication through a cascade of events. On the contrary, dexamethasone, azithromycin, and tocilizumab are recognized for their anti-inflammatory effects. They control the inflammatory response mounted against the infection and hamper the progression to uncontrolled hyperinflammation and tissue destruction. These medications may alleviate the cytokine storm syndrome that may be associated with severe and complicated SARS-CoV-2 infections. Hence, they attenuate the tissue damage that may accompany viral killing. Similarly, the newly synthesized anti-SARS-CoV-2 spike protein antibodies are inhibitors of viral fusion and internalization. Viral endocytosis is also impeded by azithromycin. Moreover, ivermectin seems to inhibit viral uptake and replication as well as pro-inflammatory cytokines production Pharmacology The removal half-life of HCQ is usually estimated Evatanepag at 40C50?days [37]. The bioavailability of oral CQ and HCQ is usually estimated at 70C80%. Hence, their use in the oral formulation can achieve adequate therapeutic concentrations in most patients [37]. CQ and HCQ display moderate binding to plasma proteins and have high volumes of distribution [36C38]. No dosage adjustment is usually indicated in patients with liver and kidney diseases. However, the drugs are metabolized by the liver and excreted in urine and feces [38]. Hence, caution should be applied when treating patients with liver or kidney dysfunction. Clinical evidence A Evatanepag retrospective cohort study including 582 pediatric patients admitted to 82 European hospitals reported that hydroxychloroquine, remdesivir, and lopinavirCritonavir were the most-used medications [39]. However, up till now, no RCTs have assessed the efficacy of these medications, among Evatanepag others, in treating pediatric COVID-19 patients. The currently available evidence is usually solely derived from adult-targeted studies. Based on the latest evidence deriving from high-quality RCTs, hydroxychloroquine has been found non-superior to standard care in the treatment of adult COVID-19 patients [40, 41]. The SOLIDARITY trial, conducted by the WHO, has the largest quantity of enrolled patients (around 12,000 patients) treated in more than 500 hospitals globally. As per the preliminary results of this trial, little or no benefit can be induced by the addition.