NEW YORK (Reuters Health) - Although no longer considered a candidate for treating the common cold, an experimental nasal spray decreases viral shedding and reduces symptoms of experimental rhinoviral infection. And now, new research suggests the drug provides a base for developing drugs to fight severe acute respiratory syndrome (SARS), according to Pfizer scientists.
“This study was monumental, in that it provides the first proof of concept that you can take an inhibitor directed toward a novel virus target and in an experimental setting produce a reduction in symptomology and a reduction in levels of virus,” Dr. Amy K. Patick, at Pfizer in San Diego, told Reuters Health.
The compound, ruprintrivir, inhibits human rhinovirus replication by blocking the 3C protease, according to a study published in the December issue of Antimicrobial Agents and Chemotherapy.
Dr. Patick’s team analyzed the prophylactic potential of ruprintrivir in 103 healthy subjects. When administered 6 hours prior to rhinovirus challenge, ruprintrivir reduced the frequency of having at least one positive viral culture 35% to 37% compared with placebo, and viral titer and RNA levels were significantly reduced. Nasal discharge weights were reduced by 41% to 55% over the 5-day study period.
And in a phase II trial of treatment efficacy, ruprintrivir administered 12 hours after viral challenge reduced symptom scores by 33% compared with placebo (p = 0.01). But Dr. Patick said that in a natural setting, where the drug was administered within 24 to 36 hours of symptom onset, results were disappointing.
“At that point, Pfizer decided to put further research on ruprintrivir on hold,” she said. “We were asking too much of a disease that has such a short window” between rhinovirus infection and symptom onset.
However, that was shortly before the SARS epidemic broke out. In response to an appeal by the U.S. government, Pfizer submitted ruprintrivir along with hundreds of other compounds they had already tested against rhinovirus, to examine their effect against SARS.
It turns out that “quite a few had moderate activity” against the SARS coronavirus, including ruprintrivir, Dr. Patick said.
As a result, Pfizer is attempting to redesign a drug to more effectively inhibit the 3c protease of the SARS coronavirus. Their research team “is working day and night... designing, synthesizing and testing inhibitors in cell culture,” Dr. Patick said.
“If we develop an inhibitor of the SARS 3c protease, there is a good likelihood that we’ll be able to show efficacy in humans,” she added.
Source: Antimicrob Agents Chemother 2003;47:3907-3916. [ Google search on this article ]
MeSH Headings:Clinical Trials: Environment and Public Health: Enzyme Inhibitors: Enzymes, Coenzymes, and Enzyme Inhibitors: Epidemiologic Methods: Evaluation Studies: Health: Health Occupations: Health Services Administration: Medicine: Investigative Techniques: Population Characteristics: Preventive Medicine: Protease Inhibitors: Public Health: Quality of Health Care: Specialties, Medical: Drugs, Investigational: Epidemiologic Study Characteristics: Clinical Trials, Phase II: Health Care Quality, Access, and Evaluation: Health Care Evaluation Mechanisms: Chemical Actions and Uses: Chemical Actions: Analytical, Diagnostic and Therapeutic Techniques and Equipment: Biological Sciences: Chemicals and Drugs: Health CareCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
