Small molecules targeting severe acute respiratory syndrome human coronavirus

Proceedings of the National Academy of Sciences of the United States of America
Chung-Yi WuChi-Huey Wong

Abstract

Severe acute respiratory syndrome (SARS) is an infectious disease caused by a novel human coronavirus. Currently, no effective antiviral agents exist against this type of virus. A cell-based assay, with SARS virus and Vero E6 cells, was developed to screen existing drugs, natural products, and synthetic compounds to identify effective anti-SARS agents. Of >10,000 agents tested, approximately 50 compounds were found active at 10 microM; among these compounds, two are existing drugs (Reserpine 13 and Aescin 5) and several are in clinical development. These 50 active compounds were tested again, and compounds 2-6, 10, and 13 showed active at 3 microM. The 50% inhibitory concentrations for the inhibition of viral replication (EC(50)) and host growth (CC(50)) were then measured and the selectivity index (SI = CC(50)/EC(50)) was determined. The EC(50), based on ELISA, and SI for Reserpine, Aescim, and Valinomycin are 3.4 microM (SI = 7.3), 6.0 microM (SI = 2.5), and 0.85 microM (SI = 80), respectively. Additional studies were carried out to further understand the mode of action of some active compounds, including ELISA, Western blot analysis, immunofluorescence and flow cytometry assays, and inhibition against the 3CL protease and vi...Continue Reading

References

Aug 1, 1974·European Journal of Pharmacology·J A Schneider, N Sperelakis
Oct 1, 1984·Contraception·S Y Chan, L C Tang
Jan 1, 1996·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·K S KhabarM N al-Ahdal
Oct 1, 1996·Clinical Pharmacology and Therapeutics·H S Fraser
Sep 1, 2001·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·C R Sirtori
Feb 6, 2003·Archives of Pharmacal Research·Young Joo LeeSeung Ki Lee
Apr 3, 2003·The New England Journal of Medicine·Susan M PoutanenUNKNOWN Canadian Severe Acute Respiratory Syndrome Study Team
Apr 3, 2003·The New England Journal of Medicine·Kenneth W TsangKar N Lai
Apr 16, 2003·The New England Journal of Medicine·Nelson LeeJoseph J Y Sung
Apr 12, 2003·The New England Journal of Medicine·Thomas G KsiazekUNKNOWN SARS Working Group
Apr 25, 2003·Lancet·J S M PeirisUNKNOWN SARS study group
May 6, 2003·Science·Marco A MarraRachel L Roper
May 8, 2003·JAMA : the Journal of the American Medical Association·Christopher M BoothAllan S Detsky
Aug 2, 2003·Lancet·J CinatlH W Doerr
Aug 22, 2003·Organic & Biomolecular Chemistry·Michael D Burkart
Aug 22, 2003·Organic & Biomolecular Chemistry·Ashraf Brik, Chi-Huey Wong
Aug 30, 2003·American Journal of Respiratory and Critical Care Medicine·James C HoKenneth W Tsang
Oct 2, 2003·Emerging Infectious Diseases·Ping Tim TsuiSik To Lai
Oct 31, 2003·Proceedings of the National Academy of Sciences of the United States of America·Haitao YangZihe Rao
Nov 14, 2003·The Journal of Antimicrobial Chemotherapy·Harri Hemilä
Dec 10, 2003·Archives of Pharmacal Research·Choon Sik JeongYeong Shik Kim
Jan 31, 2004·Science·UNKNOWN Chinese SARS Molecular Epidemiology Consortium
Apr 28, 2004·Biochemistry·Usman BachaErnesto Freire
May 19, 2004·Biochemical and Biophysical Research Communications·Chih-Jung KuoPo-Huang Liang
Jun 18, 2004·Emerging Infectious Diseases·Emily L C TanLawrence W Stanton
Mar 14, 2014·The Chinese Journal of Physiology·Wen-Hui TsaiChung-Hung Shih

❮ Previous
Next ❯

Citations

Dec 14, 2004·Applied Microbiology and Biotechnology·Julia MagdenTero Ahola
Mar 8, 2005·Drug Discovery Today·Yossef KligerDoron Gerber
Mar 16, 2005·The Lancet Infectious Diseases·David A GronebergPeter Zabel
Dec 13, 2006·Biochemistry·Jennifer BarrilaErnesto Freire
Dec 4, 2004·Nature Medicine·J S M PeirisK Y Yuen
Jan 26, 2012·Natural Product Research·Sabira BegumBina Shaheen Siddiqui
Aug 22, 2007·Antimicrobial Agents and Chemotherapy·Cheng-Wei YangShiow-Ju Lee
May 26, 2006·Antimicrobial Agents and Chemotherapy·Krzysztof PyrcLia van der Hoek
Oct 16, 2007·Clinical Microbiology Reviews·Vincent C C ChengKwok Yung Yuen
Oct 16, 2010·PloS One·Chi-Pang ChuckKam-Bo Wong
Jul 19, 2011·Future Virology·Dale L Barnard, Yohichi Kumaki
May 2, 2007·Proceedings of the National Academy of Sciences of the United States of America·Yanmei LiXiaojiang Hao
Dec 5, 2006·Veterinary Microbiology·Zhi-Gang WangQi-Yu Bao
Dec 7, 2005·Biochemical and Biophysical Research Communications·Ping WeiLuhua Lai
Oct 1, 2006·Drug Discovery Today. Technologies·Shuai ChenHualiang Jiang
Jul 20, 2006·Journal of Virological Methods·Yih-Shyun E ChengChi-Huey Wong
Jul 14, 2006·Antiviral Research·Bart L Haagmans, Albert D M E Osterhaus
Nov 3, 2005·Current Opinion in Structural Biology·Mark BartlamZihe Rao
Aug 30, 2005·Current Opinion in Microbiology·Erik De Clercq
Sep 14, 2012·Biological & Pharmaceutical Bulletin·Ji-Young ParkYoung Bae Ryu
Jun 19, 2008·Chemistry & Biology·Koen H G VerschuerenRolf Hilgenfeld
Nov 27, 2007·Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology·Hye-Young KimKyongmin Kim
Jul 6, 2014·Current Opinion in Virology·Adeyemi O Adedeji, Stefan G Sarafianos
Sep 10, 2013·Antiviral Research·Rolf Hilgenfeld, Malik Peiris
Oct 19, 2004·Chemistry & Biology·Jan E BlanchardEric D Brown

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.