However, there are some differences between these two agents regarding the mode of action, receptor affinity and dose of administration. by inhibiting the SARS-CoV-2 entry and interacting with glycosylation of ACE2 receptor and it’s binding with RBD [10,30]. HCQ may help s to destroy the computer AG-126 virus into the cytoplasm, through the action of lysosomes and blocks its presentation through the major histocompatibility complex (MHC) to T-cells [31]. Both drugs were used widely in the first days of the pandemic, but the results of the trials were inconclusive [11,32]. (3) studies [33]. It is approved by the FDA for the treatment of adult hospitalized COVID-19 patients and in pediatric populace aged? ?12 years. It has been studied in many clinical trials with promising results in some patients [33], AG-126 [34], [35], [36]. Other antiviral brokers have been proposed and used in hospitalized COVID-19 patients such as, lopinavir and/or ritonavir in combination with ribavirin. (4) em Lopinavir-Ritonavir /em In a randomized controlled open-label trial involving hospitalized adult COVID-19 patients, Cao et?al. evaluated the effectiveness of lopinavir-ritonavir (400?mg and 100?mg) in addition to standard of care (SC), twice daily for 14 days versus SC alone. A total of 199 patients were randomized in which 99 were assigned to lopinavir-ritonavir group, while 100 to the SC group. No benefit was observed with lopinavir-ritonavir treatment beyond SC [37]. (5) em Triple therapy /em An open-label randomized, phase-2 trial using triple combination of interferon beta-1b, lopinavir-ritonavir and ribavirin conducted by Hung et?al. in hospitalized patients with moderate to moderate COVID-19 disease. At that time, 86 patients were assigned to receive combination triple therapy, while 41 were assigned to receive lopinavir-ritonavir alone. Triple antiviral therapy was superior to lopinavir-ritonavir in alleviating symptoms AG-126 and shortening the duration of viral shedding and hospital stay in patients with moderate to moderate COVID-19 [38]. Other antiviral agents have been AG-126 investigated in several clinical trials for the treatment of COVID-19 and some of them have received emergency use authorization from the FDA for the treatment of nonhospitalized patients. (6) em Ritonavir-boosted nirmatrevil /em Ritonavir-boosted nirmatrevil, is an orally used drug for high risk non-hospitalized adults with COVID-19. Treatment of symptomatic COVID-19 ritonavir-boosted nirmatrevil resulted in high risk progression to severe COVID-19 that was 89% lower than placebo [39]. (7) em Molnupiravir /em Molnupiravir, is an orally used drug for several RNA viruses, including SARS-CoV-2. It is used in high risk nonhospitalized patients. Indeed, early treatment with molnupiravir reduced the risk of hospitalization or death in unvaccinated COVID-19 adult patients [40]. (B) Targeting cell membrane receptors, sensors and signaling (1) em Colchicine /em It is a tricyclic alkaloid, a potent anti-inflammatory AG-126 agent used in rheumatology for TSPAN9 many years to treat gout, pseudogout and Familial Mediterranean Fever (FMF) as well as some heart disorders [41]. Colchicine is usually a potent inhibitor of tubulin polymerization. Microtubules are the main tools of cytoskeleton involved in many cellular processes [42]. Furthermore, colchicine inhibits neutrophil and monocyte chemotaxis and the expression of adhesion molecules in the setting of inflammation. It inhibits also Nod-Like Receptor (NLR) protein-3 inflammasome (NLRP3) suppressing Caspase-1 activation, resulting in inhibition of IL-1 [41,42]. Colchicine used in patients with gout and FMF, who contracted SARS-CoV-2 contamination, may mitigate the COVID-19 computer virus and its outcome [43,44]. Given the above mechanism of action, colchicine was studied in non-hospitalized and hospitalized patients with COVID-19, and the results showed some beneficial effects on disease outcome [45]. In a large placebo-controlled trial (COLCORONA), Tardif et?al. evaluated the use of colchicine (0,5?mg twice daily) in patients with positive test for SARS-CoV-2 contamination at the time of inclusion, regardless of symptoms, with at least one risk factor for COVID-19. The study included 4488 patients of which.