DOI: 10.1128/aac.46.3.841-847.2002. RFI-641, a Potent Respiratory Syncytial Virus Inhibitor

RFI-641, a Potent Respiratory Syncytial Virus Inhibitor

10.1128/aac.46.3.841-847.2002

Crossref journal-article

American Society for Microbiology

Antimicrobial Agents and Chemotherapy (235)

Abstract

ABSTRACT Human respiratory syncytial virus (RSV), a paramyxovirus, is a major cause of acute upper and lower respiratory tract infections in infants, young children, and adults. RFI-641 is a novel anti-RSV agent with potent in vitro and in vivo activity. RFI-641 is active against both RSV type A and B strains. The viral specificity and the large therapeutic window of RFI-641 (>100-fold) indicate that the antiviral activity of the compound is not due to adverse effects on normal cells. The potent in vitro activity of RFI-641 can be translated to efficacy in vivo: RFI-641 is efficacious when administered prophylactically by the intranasal route in mice, cotton rats, and African green monkeys. RFI-641 is also efficacious when administered therapeutically (24 h postinfection) in the monkey model. Mechanism of action studies indicate that RFI-641 blocks viral F protein-mediated fusion and cell syncytium formation.

Bibliography

Huntley, C. C., Weiss, W. J., Gazumyan, A., Buklan, A., Feld, B., Hu, W., Jones, T. R., Murphy, T., Nikitenko, A. A., OâHara, B., Prince, G., Quartuccio, S., Raifeld, Y. E., Wyde, P., & OâConnell, J. F. (2002). RFI-641, a Potent Respiratory Syncytial Virus Inhibitor. Antimicrobial Agents and Chemotherapy, 46(3), 841â847.

Authors 15

Clayton C. Huntley (first)
William J. Weiss (additional)
Anna Gazumyan (additional)
Aron Buklan (additional)
Boris Feld (additional)
William Hu (additional)
Thomas R. Jones (additional)
Timothy Murphy (additional)
Antonia A. Nikitenko (additional)
Bryan O'Hara (additional)
Gregory Prince (additional)
Susan Quartuccio (additional)
Yuri E. Raifeld (additional)
Philip Wyde (additional)
John F. O'Connell (additional)

References 31 Referenced 59

Aulabaugh, A., W. Ding, G. Ellestad, A. Gazumyan, C. Hess, G. Krishnamurthy, B. Mitsner, and J. Zacardi. 2000. Inhibition of respiratory syncytial virus by a new class of chemotherapeutic agents. Drugs Future25:287-294. (10.1358/dof.2000.025.03.572014) / Drugs Future (2000)
Aylward, B., and D. Burdge. 1991. Ribavirin therapy of adult respiratory syncytial virus pneumonitis. Arch. Intern. Med.151:2303-2304. (10.1001/archinte.1991.00400110139027) / Arch. Intern. Med. (1991)
10.1128/jvi.71.12.8973-8982.1997
Ding, W., B. Mitsner, G. Krishnamurthy, A. Aulabaugh, C. Hess, J. Zaccardi, M. Cutler, B. Feld, A. Gazumyan, Y. Raifeld, A. Nikitenko, S. Lang, Y. Gluzman, B. O'Hara, and G. Ellestad. 1998. Novel and specific respiratory syncytial virus inhibitors that target virus fusion. J. Med. Chem.41:2671-2675. (10.1021/jm980239e) / J. Med. Chem. (1998)
10.1093/infdis/174.3.456
10.1128/CMR.13.3.371
10.2174/1381612003400704
Hall, C. 1999. Respiratory syncytial virus: a continuing culprit and conundrum. J. Pediatr.135:2-7. / J. Pediatr. (1999)
10.1006/viro.1994.1245
10.1073/pnas.94.25.13961
Kimpen, J. 1996. Experimental models for respiratory syncytial virus infections. Rev. Med. Microbiol.7:115-122. (10.1097/00013542-199604000-00006) / Rev. Med. Microbiol. (1996)
10.1007/s007050050156
10.1073/pnas.93.5.2186
LaVia, W., M. Marks, and H. Stutman. 1992. Respiratory syncytial virus puzzle: clinical features, pathophysiology, treatment and prevention. J. Pediatr.121:503-510. (10.1016/S0022-3476(05)81135-7) / J. Pediatr. (1992)
LaVia, W., S. Grant, H. Stutman, and M. Marks. 1993. Clinical profile of pediatric patients hospitalized with respiratory syncytial virus infection. Clin. Pediatr.8:450-454. / Clin. Pediatr. (1993)
10.1021/bi000471y
10.1128/JVI.74.13.5911-5920.2000
McIntosh, K. 1997. Respiratory syncytial virus, p. 691-705. In A. Evans and R. Kaslow (ed.), Viral infections of humans, 4th ed. Plenum Medical Book Company, New York, N.Y. / Viral infections of humans (1997)
Nikitenko, A., Y. Raifeld, and T. Wang. 2001. The discovery of RFI-641 as a potent and selective inhibitor of the respiratory syncytial virus. Bioorg. Med. Chem. Lett.11:1041-1044. (10.1016/S0960-894X(01)00150-0) / Bioorg. Med. Chem. Lett. (2001)
Ohmit, S., F. Moler, A. Monto, and A. Khan. 1996. Ribavirin utilization and clinical effectiveness in children hospitalized with respiratory syncytial virus infection. J. Clin. Epidemiol.49:963-967. (10.1016/0895-4356(96)00137-0) / J. Clin. Epidemiol. (1996)
10.1038/71503
Prince, G., B. Jenson, R. Horswood, E. Camargo, and R. Chanock. 1978. The pathogenesis of respiratory syncytial virus infection in cotton rats. Am. J. Pathol.93:771-783. / Am. J. Pathol. (1978)
10.1016/S1074-5521(01)00042-4
10.1517/13543784.9.2.221
10.1177/095632029901000305
10.1128/jvi.47.1.171-177.1983
10.1089/aid.1993.9.1051
10.1016/S0166-3542(98)00029-1
10.1016/S0166-3542(98)00002-3
10.1073/pnas.260499197
Zolnai, A., E. Toth, R. Wilson, and V. Frenyo. 1998. Comparison of 3H-thymidine incorporation and CellTiter 96 aqueous colorimetric assays in cell proliferation of bovine mononuclear cells. Acta Vet. Hung.46:191-197. / Acta Vet. Hung. (1998)

Dates

Type	When
Created	23 years ago (July 27, 2002, 5:56 a.m.)
Deposited	3 years, 6 months ago (Feb. 21, 2022, 12:37 p.m.)
Indexed	3 months, 2 weeks ago (May 10, 2025, 12:28 a.m.)
Issued	23 years, 5 months ago (March 1, 2002)
Published	23 years, 5 months ago (March 1, 2002)
Published Print	23 years, 5 months ago (March 1, 2002)

Funders 0

None

BibTeX

@article{Huntley_2002, title={RFI-641, a Potent Respiratory Syncytial Virus Inhibitor}, volume={46}, ISSN={1098-6596}, url={http://dx.doi.org/10.1128/aac.46.3.841-847.2002}, DOI={10.1128/aac.46.3.841-847.2002}, number={3}, journal={Antimicrobial Agents and Chemotherapy}, publisher={American Society for Microbiology}, author={Huntley, Clayton C. and Weiss, William J. and Gazumyan, Anna and Buklan, Aron and Feld, Boris and Hu, William and Jones, Thomas R. and Murphy, Timothy and Nikitenko, Antonia A. and O’Hara, Bryan and Prince, Gregory and Quartuccio, Susan and Raifeld, Yuri E. and Wyde, Philip and O’Connell, John F.}, year={2002}, month=mar, pages={841–847} }

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}