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1、Review Development of chemical inhibitors of the SARS coronavirus: Viral helicase as a potential target Young-Sam Keum a, Yong-Joo Jeong b,* aCollege of Pharmacy, Dongguk University, Goyang, Gyeonggi-do 410-820, Republic of Korea bDepartment of Bio and Nanochemistry, Kookmin University, Seoul 136-70
2、2, Republic of Korea Contents 1. A novel coronavirus as a culprit for severe acute respiratory syndrome (SARS) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1351 2. Characterization of the SCV helicase protein . . . . . . . . . . . . . . . . . . . . . .
3、. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1352 3. Unwinding of double-stranded nucleic acids (dsNAs) mediated by SCV helicase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1352 4. NTP hydrolysis
4、 activity of the SCV helicase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1355 5. Development of chemical inhibitors of the SCV helicase, nsP13 . . . . . . . . . . . . . . . . . . . . . . . . .
5、. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1355 6. Future perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1356 Acknowledge
6、ments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1357 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
7、. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1357 1. A novel coronavirus as a culprit for severe acute respiratory syndrome (SARS) Severe acute respiratory syndrome (SARS) is an atypical contagious respiratory illness primarily trans
8、mitted by respiratory droplets or close personal contact 1. It emerged at the end of 2002 from Guangdong province in Southern China and rapidly spread to Canada and to Southeast Asian countries, including Singapore, Vietnam, Hong Kong, and Taiwan. The affected patients initially showed mild fl u-lik
9、e symptoms, such as cough, sore throat, and fever, and the incubation period for this disease was usually about 27 days. The symptoms progressed to acute respiratory distress syndrome (ARDS) in about 25% of the affected patients, which necessitated mechanical ventilation for survival. More than 50%
10、of the patients who developed ARDS eventually died. The global SARS pandemic was brought under control in July of 2003 by undertaking public health measures, including isolation of patients. A total of 8096 patients were diagnosed with SARS, of which 774 died (total mortality rate, 9.6%). Another im
11、portant clinical feature of SARS is that compared to elderly patients, young patients had a favorable prognosis (mortality rates for elderly patients: up to 50%) 2. The total number of SARS patients and casualties worldwide are available on the offi cial website of the World Health Organization (WHO
12、): http:/www.who.int/csr/sars/ country/en. During the SARS outbreak, clinicians were unaware of which treatments were required to treat SARS patients, because they had no prior experience in dealing with this disease. After the SARS Biochemical Pharmacology 84 (2012) 13511358 A R T I C L E I N F O A
13、rticle history: Received 30 May 2012 Accepted 15 August 2012 Available online 23 August 2012 Keywords: Severe acute respiratory syndrome (SARS) Coronavirus nsP13 Myricetin Scutellarein A B S T R A C T Severe acute respiratory syndrome (SARS) was the fi rst pandemic in the 21st century to claim more
14、than 700 lives worldwide. However, effective anti-SARS vaccines or medications are currently unavailable despite being desperately needed to adequately prepare for a possible SARS outbreak. SARS is caused by a novel coronavirus, and one of its components, a viral helicase, is emerging as a promising
15、 target for the development of chemical SARS inhibitors. In the following review, we describe the characterization, family classifi cation, and kinetic movement mechanisms of the SARS coronavirus (SCV) helicasensP13. We also discuss the recent progress in the identifi cation of novel chemical inhibi
16、tors of nsP13 in the context of our recent discovery of the strong inhibition of the SARS helicase by natural fl avonoids, myricetin and scutellarein. These compounds will serve as important resources for the future development of anti-SARS medications. ? 2012 Elsevier Inc. All rights reserved. * Corresponding author. Tel.: +82 2 910 5454; fax: +82 2 910 4415. E-mail addresses: , jeongyjkookmin.ac.kr (Y.-J. Jeong). Contents lists available at SciVerse ScienceDirect Biochemical Pharmaco
