|
|
| Type |
Poster Presentation |
| Area |
의약화학 |
| Room No. |
포스터발표장 |
| Time |
4월 20일 (목요일) 11:00~12:30 |
| Code |
MEDI.P-459 |
| Subject |
A Novel Class of Highly Potent Small Molecule Inhibitors of Rhinovirus Replication
|
| Authors |
김진우, 정영식1,*
한국화학연구원 의약화학연구센터, Korea
1한국화학연구원 신물질연구단, Korea
|
| Abstract |
Human rhinovirus (hRV) is a main causative agent of upper respiratory illness, namely common colds. The hRV infection also has been known to exacerbate asthma, acute otitis media and chronic obstructive pulmonary diseases (COPD), accompanying airway obstruction and hyperresponsiveness. The development of anti-hRV drugs has been hampered by the extreme diversity in hRV serotypes. Although several compounds have been shown anti-hRV activity, none of them have been approved yet.
In this study, we disclose a novel series of 6-{[2-(methylcarbamoyl)pyridin-4-yl]oxy}benzo[b]thiophene-2-carboxylic ester derivatives against viral replication of hRV-A and hRV-B species. We found that compound KR-25763 have 2-digit nanomolar reactivity against both hRV species (EC50 = 0.053, 0.08 and 0.016 μM for hRV-B14, hRV-A21 and hRVA71, respectively). Time-of-addition study revealed that KR-25763 act as the early stage of the replication, namely the viral entry. Mutation study showed a single point mutation on Leu25 of viral capsid protein 3 (VP3) and computational study suggested the key interaction between KR-25763 and VP3 N-terminal chain. Cross resistance experiments displayed only partial cross resistance with pleconaril and vapendavir, previously reported potent capsid binding inhibitors. In addition, anti-poliovirus 3 (PV3) reactivity of KR-25763 implies its potential for the braod-spectrum reactivity against hRVs and other enterovirus species.
|
| E-mail |
sidera@krict.re.kr |
|
119th General Meeting of the KCS