, 2003). In view of the weak antiviral activity of protease inhibitors, further studies should be done to ascertain whether

PI3K inhibitor the clinical benefit could be attributed to their anti-apoptotic rather than their antiviral activity ( Matarrese et al., 2003). In the early phase of the SARS epidemic, before the identification of the causative agent, histopathological changes in open lung biopsy specimens suggested the possibility of immunopathological damage (Nicholls et al., 2003). Immunomodulators including corticosteroid, convalescent plasma, and pentaglobulin were therefore empirically used as initial and rescue treatment. As initial therapy, a corticosteroid without antiviral therapy was initiated in 417 (16.4%) of 2546 patients (Chen et al., 2006, Loutfy et al., 2003 and Wang et al., 2004a), while recombinant interferon-alpha was given Y-27632 to 30 (1.2%) (Zhao et al., 2003) and a combination of corticosteroid and interferon was given in 114 (4.5%) (Loutfy et al., 2003 and Zhao et al., 2003). In a preliminary uncontrolled study of 24 patients in Toronto, 13 patients were treated with corticosteroid alone and 9 patients were treated with corticosteroid and interferon alfacon-1. Among the corticosteroid group,

5 (38.5%) required intensive care, 3 required mechanical ventilation, and one died, while there was no mortality among the corticosteroid plus interferon alfacon-1 group and only 3 and 1 patient required intensive care and mechanical ventilation respectively. In addition, the combination of corticosteroid and interferon Urease alfacon-1 appeared to result in improvements in oxygenation requirement and faster resolution of chest radiograph abnormalities

(Loutfy et al., 2003). However, in vitro susceptibility testing of interferons against SARS-CoV showed inconsistent results for interferon-ß1a and interferon-α2b ( Cinatl et al., 2003, Hensley et al., 2004 and Stroher et al., 2004), although inhibition of cytopathic effects of SARS-CoV in culture was observed for interferon-ß, interferon-αn1, interferon-αn3, and leukocytic interferon-α ( Tan et al., 2004). Treatment with both interferon-ß and interferon-γ synergistically inhibited SARS-CoV plaque formation by 30-fold and replication by 3000-fold at 24 h, and by more than 105-fold at 48 and 72 h post-infection in Vero E6 cells ( Sainz et al., 2004). Prophylactic treatment of SARS-CoV-infected macaques with pegylated interferon-alpha reduced viral replication and excretion, and viral antigen expression by type 1 pneumocytes ( Haagmans et al., 2004). Before the longitudinal serial viral load profile of SARS-CoV during the course of infection was known, corticosteroid therapy was often used together with ribavirin.