Initial viral load and the outcomes of SARS

Chu, Chung Ming; Poon, Leo L. M.; Cheng, Vincent Chi-Chung; Chan, K. S.; Hung, Ivan; Wong, Maureen Mo-Lin; Chan, Kwok Hung; Leung, Wai Shing; Tang, Bone Siu-Fai; Chan, Vivien; Ng, Woon Leung; Sim, Tiong Chee; Ng, Ping Wing; Law, Kin Ip; Tse, Doris M.W.; Peiris, J. S. Malik; Yuen, Kwok‐Yung

doi:10.1503/cmaj.1040398

Cited by 188 publications

(192 citation statements)

References 18 publications

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“…These compounds with high SI values apparently inhibit SARS-CoV replication with little or no cytotoxicity against Vero E6 cells and thus have good potential as lead compounds in the future development of anti-SARS drugs. Pinusolidic acid (9) has been reported as a platelet-activating factor inhibitor, 30 and forskolin (10), a well-known labdane-type diterpene, was reported to activate adenylate cyclase and increase cyclic AMP levels in several cell types. 31 In this report, we observed potent anti-SARS virus activity for these two compounds.…”

Section: Discussionmentioning

confidence: 99%

“…6,7 The combination therapy of HIV protease inhibitor drugs (lopinavir/ritonavir) plus ribavirin plus corticosteroids may improve some clinical outcomes, but only when administrated in the early phase of the illness. 8,9 Since the emergence of SARS considerable effort has been put into antiviral research to screen and evaluate compounds for anti-SARS-CoV activity in an attempt to prevent a re-emergence of the disease. Glycyrrhizin from licorice roots has been shown to inhibit SARS-CoV replication with a 50% effective concentration (EC 50 ) of 365 µM, 6 and a number of glycyrrhizin derivatives have been shown to possess modestly higher antiviral bioactivity.…”

Section: Introductionmentioning

confidence: 99%

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Specific Plant Terpenoids and Lignoids Possess Potent Antiviral Activities against Severe Acute Respiratory Syndrome Coronavirus

et al. 2007

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In this study, 221 phytocompounds were evaluated for activity against anti-severe acute respiratory syndrome associated coronavirus (SARS-CoV) activities using a cell-based assay measuring SARS-CoV-induced cytopathogenic effect on Vero E6 cells. Ten diterpenoids (1-10), two sesquiterpenoids (11 and 12), two triterpenoids (13 and 14), five lignoids (15-19), curcumin (20), and reference controls niclosamide (21) and valinomycin (22) were potent inhibitors at concentrations between 3.3 and 10 µM. The concentrations of the 22 compounds to inhibit 50% of Vero E6 cell proliferation (CC 50 ) and viral replication (EC 50 ) were measured. The selective index values (SI ) CC 50 /EC 50 ) of the most potent compounds 1, 5, 6, 8, 14, and 16 were 58, >510, 111, 193, 180, and >667, respectively. Betulinic acid (13) and savinin (16) were competitive inhibitors of SARS-CoV 3CL protease with K i values ) 8.2 ( 0.7 and 9.1 ( 2.4 µM, respectively. Our findings suggest that specific abietane-type diterpenoids and lignoids exhibit strong anti-SARS-CoV effects.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Specific Plant Terpenoids and Lignoids Possess Potent Antiviral Activities against Severe Acute Respiratory Syndrome Coronavirus

et al. 2007

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“…A number of clinical/laboratory parameters have been shown have a prognostic value. Poor prognostic factors include advanced age [3,23,31,141], chronic hepatitis B treated with lamivudine [31], severe hepatitis [27], high initial LDH [141], high peak LDH [3], high neutrophil count on presentation [3,141], diabetes mellitus or other co-morbid conditions [5,142], low CD4 and CD8 lymphocyte counts at presentation [143] and a high initial SARS-CoV viral load [97,144].…”

Section: Short-term Outcomementioning

confidence: 99%

SARS: clinical presentation, transmission, pathogenesis and treatment options

2006

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SARS (severe acute respiratory syndrome) appeared as the first emerging infectious disease of this century. It is fortunate that the culprit virus can be grown without much difficulty from a commonly used cell line, allowing an unlimited supply of isolates for further molecular studies and leading to the development of sensitive diagnostic assays. How the virus has successfully jumped the species barrier is still a mystery. The superspreading events that occurred within hospital, hotel and high-density housing estate opens a new chapter in the mechanisms and routes of virus transmission. The old practice of quarantine proved to be still useful in controlling the global outbreak. Despite all the available sophisticated tests, alertness with early recognition by healthcare workers and prompt isolation of suspected cases is still the most important step for containing the spread of the infection. Although the rapidly evolving outbreak did not allow the conducting of systematic clinical trails to evaluate treatment options, the accumulated experience on managing SARS patients will improve the clinical outcome should SARS return. Although SARS led to more than 700 deaths worldwide, the lessons learnt have prepared healthcare systems worldwide to face future emerging and re-emerging infections.

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“…In addition, it is not clear what role host immunity against SARS-CoV played in viral clearance or tissue damage. High initial viral load was shown to be independently associated with severity of the disease, and may be influenced by host immune responses (5). However, recent studies have suggested that type I IFN played a key role in the switch from innate immunity to adaptive immunity during the acute phase of SARS, and patients with poor outcomes showed type I IFN-mediated immunopathological events and deficient adaptive immune responses (6, 7).…”

mentioning

confidence: 99%