Potential drugs can aim at a newly-discovered enzyme that the parasite uses to metabolise energy at every stage of its infection in humans, they said.
The finding, published in the journal Nature, is important because only a tiny handful of weaknesses have been found that apply to every stage of the complex process by which the Plasmodium parasite grows and multiplies in the body.
Most drugs aim at specific stages in the parasite's cycle, not all.
They notably fail to wipe out early forms of the parasite called hypnozoites that remain dormant in the liver and then revive, triggering a malarial relapse.
The new target, called phosphatidylinositol-4-kinase, or PI4K, is an enzyme that the parasite needs to survive in host cells.
"Most drugs selectively work on certain stages of the (parasite's) life cycle, but not all stages," said Case McNamara, a genomics specialist at the Novartis Research Foundation in San Diego, California.
"Inhibitors of this drug target have the potential to not only cure individuals of a malaria infection, but also to prevent infections and even block transmission of the parasite back to the mosquito."
The only drug that is currently licensed to wipe hypnozoites is primaquine.
Licensed more than half a century ago, the formula is considered a last-throw-of-the-dice option, as it can cause potentially life-threatening anaemia for people with an inherited genetic mutation.
According to the UN's World Health Organisation (WHO), 219 million people became infected with malaria in 2010, of whom 660,000 died, most of them African children under the age of five.