C O M P U T E R S I N C H E M I S T R Y

VIRTUAL HUNT FOR SMALLPOX DRUGS Massive search using idle computer time turns up drug candidates

T HE SEARCH FOR A DRUG TO combat the smallpox virus got a boost last week, as a

public-private consortium turned over several dozen promising can­didates from its massive virtual screening effort to the Depart­ment of Defense.

DOD's U.S. Army Medical Re­search Institute of Infectious Dis­eases, which funded the smallpox project, hopes the leads will ease the search for drugs against this potential bioweapon.

Using screensaver software to harness the idle time of 2.5 million computers, the consortium— which includes Oxford University, Accelrys, IBM, and United De­vices—screened a database of 35 million molecules as potential in­

hibitors of a key smallpox enzyme. Personal computer users in over 190 countries voluntarily down­loaded the screensaver software.

This collective effort, previ­ously used to search for anthrax drugs (C&EN, Jan. 28, 2002 , page 12), has "opened up areas of discovery and analysis in time frames that were previously im­possible," according to Oxford chemistry professor W Graham Richards. In this case, a screen that would take 39,000 years on a single computer was completed in just six months.

lies on this enzyme to "unwind" its tightly coiled genome. Topo-isomerase I binds the tightly coiled genom­ic DNA and snips one strand of the D N A duplex. The DNA can then be unwound and eventually stitched back together.

This process is es­sential for viral repli­cation, suggesting that topoisomerase I inhi­bitors might make good smallpox drugs. The consortium's vir­tual screening effort turned up 44 mole­cules that bind at the active site of a model of smallpox topoisom­erase I. These methods also are be­ing used to sift out molecules that inhibit viral topoisomerase I but not its human counterpart.

The consortium is now search­ing for partners to fund other vir­tual drug screens, including ones for tuberculosis, malaria, and SARS.-AMANDAYARNELL

SMALLPOX TARGET Molecules that bind in the active site of viral topoisomerase I (shown in green with catalytic residues in green ball-and-stick form) but don't interact with the human enzyme (shown in purple and pink) might make the best drugs.

B U S I N E S S

AGBIOTECH WINS ON MANY FRONTS Monsanto stays its course while it and others see favorable rulings

FOR NEARLY 3 Ο YEARS, MON-santo relied on Roundup herbicide as its major prof­

it generator. Now, after more than a decade spent building a genet­ic traits and crop seeds business, the firm is seeing its profits driv­en largely by its agbiotech side.

This year, the gross profit gen­erated by the seeds and traits business, at just over $1 billion, will surpass the roughly $750 mil­lion brought in by Roundup, CEO Hugh Grant recently told analysts and investors.

Still, even 12 years after key patents expired, the herbicide con­tributes significantly to Monsan-

to's cash position. It's taking the steps to "ensure that the Roundup business is focused on maximizing cash, while at the same time pro­viding an opportunity for our R&D investments in seeds and traits to grow," Grant said.

Merrill Lynch analyst Donald D. Carson says Monsanto's rapid transformation into a "high-mar­gin, high-growth agbiotech com­pany" will lead to an estimated 23% increase in 2004 earnings. Wider adoption of Monsanto crops, higher technology use fees, and a significant recovery in South American markets will offset de­clining herbicide prices, he says.

Last week, Brazil's government signed a provisional measure le­galizing the planting of herbicide-tolerant soybeans this year. Even though full legislative approval of the technology has yet to occur, genetically engineered crops are becoming entrenched in the large Brazilian market. Meanwhile, Europe's moratorium on engineered crops might soon be lifting.

The Brazilian ac­tion noted that farm­ers may have to pay technology use fees. In the U.S., such fees are the crux of a 1999 lawsuit brought by farmers against Monsanto, Syn-genta, Aventis, and DuPont's Pio­neer Hi-Bred unit. Last week, a district court judge denied class-action status related to price-fix­ing after previously throwing out claims that agbiotech products disrupted corn and soybean mar­kets and caused economic loss.— ANN THAYER

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