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A cure for the common cold?

An experimental drug has shown broad antiviral effects on a large number of the picornaviruses against which it has been tested. The tests, say scientists, while still preliminary, could yield the first drug capable of treating this family of disease agents, whose members can cause a wide variety of illnesses ranging in seriousness from polio, hepatitis A, viral meningitis and neonatal sepsis (a generally fatal disease affecting newborns) to those mild rhinovirus infections responsible for half of all common colds.

Based on the efficacy demonstrated thus far in animals and cell-culture experiments, the drug--known as WN 51,711--"holds the potential for curing the common cold" and a broad spectrum of other previously untreatable infections, says Guy Diana, group leader for medicinal chemistry at the Sterling-Winthrop Research Institute in Rensselaer, N.Y. Diana reported on relationships between the drug's chemical structure and its antiviral activity in a presentation last week at the American Chemical Society's 189th national meeting in Miami.

To reproduce, an infectious virus first adheres to a cell's membrane. Then it penetrates the cell, shedding its own outer protein covering and releasing its store of genetic material. If allowed to replicate and reencapsulate, this genetic material would form new viruses that could infect other cells. The new drug halts the reproduction and spread of a virus by preventing the initial uncoating of the protein shell that encapsulates its genetic material.

By halting viral reproduction so early in the viral-uncoating phase, the drug's mechanism of action may be unique, says Mark A. McKinlay, a virologist on the project. Exactly why it selectively binds with viruses and prevents their uncoating, however, is not fully understood.

Used therapeutically, the drug halted development of paralysis in mice that had recently been infected with polio-2 or a paralytic ECHO-9 picornavirus. Used prophylactically, the drug prevented viral infection altogether when given to mice immediately before and again immediately after their exposure to various picornaviruses.

Since there are no animal models other than chimpanzees for studying rhinovirus infections. McKinlay says tests of the drug's efficacy against these cold viruses were performed using several types of cultured human cells. To date, WIN 51,711 appears rhinoviruses tested. Testing isn't over, however; there are more than 120 rhinoviruses capable of causing colds.

So far, McKinlay says WIN 51,711 is somewhat more effective against enteroviruses -- the picornavirus family's major class of nonrhinoviruses causing human disease -- than against cold viruses. Last week Diana reported data on a close analog of the drug that showed the opposite effect -- slightly better action against rhinviruses. This leads to speculation that the end product of the research may not be a single antipicornavirus drug but instead a group of related compounds, each of whose activity has been optimized for a target class of the viruses.

Initial toxicity tests suggest the new drug is safe. The next step is clinical trials. A critical question to be answered there will be whether, by the time symptoms appear, these viral diseases are already too advanced to treat.
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Title Annotation:WIN 51,711
Author:Raloff, Janet
Publication:Science News
Date:May 11, 1985
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