N a fixed-dose combination withAPNACE2 has been identified because the key receptor for SARSCoV both in vitro and in vivo (75, 76). ACE2 not simply acts as the entry receptor of SARS-CoV but additionally protectsFrontiers in Medicine | www.frontiersin.orgMarch 2021 | Volume eight | ArticleYe et al.Advances in COVID-against acute lung injury by minimizing destructive inflammatory reactions (77). The receptor-binding domain (RBD) in the spike protein of SARS-CoV-2 is extremely equivalent for the RBD of SARSCoV, indicating that both viruses possibly use the popular host cell receptor ACE2. Recent research confirmed that the spike protein of SARS-CoV-2 straight contacts ACE2 to enter cells, and SARS-CoV-2 recognizes human ACE2 even more effectively than SARS-CoV, suggesting an enhanced capacity of person-to-person SARS-CoV-2 transmission (6, 78, 79). Remedy with human recombinant soluble ACE2 (hrsACE2) has been proposed to suppress SARS-CoV-2 infections for the reason that excessive ACE2 can not only competitively bind with SARSCoV-2 to block the virus from entering the host cells but in addition protect the lung from injury by recovering cellular ACE2 activity (80). hrsACE2 could properly inhibit SARS-CoV-2 replication in Vero cells, engineered human blood vessels and kidney organoids (77). Hence, APN01 (hrsACE2) developed by Apeiron Biologics has undergone a placebo-controlled, double-blinded, phase II Na+/Ca2+ Exchanger Storage & Stability clinical trial to evaluate its clinical efficacy and safety within the treatment of COVID-19 individuals (ClinicalTrials.gov: NCT04335136).has the potential for combination therapy with direct-acting antivirals, for instance lopinavir/ritonavir or remdesivir, presently getting used and investigated through the COVID-19 pandemic simply because of its minimal interaction together with the relevant cytochrome P450 (CYP) drug-metabolizing enzymes (85). Cantini et al. performed a pilot study on the safety and clinical efficacy of baricitinib therapy combined with lopinavir-ritonavir in patients with moderate COVID-19 pneumonia (86). Even so, the limitations of this study, like its open-label, nonrandomized feature, lack of correctly developed manage group, and restricted patient quantity treated with baricitinib, need larger randomized controlled trials to further demonstrate the efficacy of baricitinib treatment.CONVALESCENT Lipoxygenase Synonyms plasma THERAPYAs a classic passive immunotherapy, convalescent plasma therapy has been utilised to stop and treat a lot of infectious diseases since the 1890s (87). Convalescent plasma therapy was successfully applied to the treatment of SARS, H5N1 influenza, 2009 H1N1 pandemic, and MERS, with enhanced clinical situations and reduced mortality (881). Nonetheless, inside the Ebola virus illness setting, convalescent plasma therapy failed to achieve significant survival improvement (92). Since SARS, MERS, and COVID-19 share related clinical and virological functions (93), convalescent plasma therapy may very well be a possible therapy alternative for COVID-19 sufferers (94). 1 recent laboratory study indicated that sera from several patients can neutralize the COVID-19 virus isolated from the bronchoalveolar lavage fluid of a critically ill patient (1). A systematic review (95) was conducted to assess the clinical efficacy of convalescent plasma therapy for sufferers with COVID-19. Primarily based on five offered clinical research (87, 969), convalescent plasma therapy seems to become promising, with decreased mortality, enhanced clinical status, and virus clearance. Several randomized clinical trials happen to be conducted to evalu.