Simple structure, complex life cycle (Photo: Phil Moyer)

In the beginning of this year the Journal of Medicinal Chemistry published an article by a group of US American scientists which gives new insights into the interaction between the fatal Ebolavirus and other molecules. Possibly, this innovation in the field will provide a basis for future developments in antiviral drug production.

Ebola was first recognized in Central Africa where most of its outbreaks have been prevalent. The Ebolavirus is transmitted from an animal host, most likely bats, to humans who can then infect others via their body fluids. Infected individuals develop the typical symptoms of a viral hemorrhagic fever which includes high fever, diarrhea and a severe rash all over the body. This will consequently lead to a hypovolemic shock and in up to 90% of the cases to death of the individual.

Although the disease spreads easily, especially in countries with limited hygienic standards, neither effective prevention methods nor treatments have been developed so far. The danger of the Ebolavirus does not only lie in its high virulence and mortality rate but that it is silently carried in other animal species making it impossible to monitor its incidence. Amongst other strains, Ebola presents a further threat to human survival as it possesses the potential to be used as a bioterrorism weapon.

Motivated by the threats which viruses present to human survival, scientists have been undertaking extensive research in the field since 1892. Viruses are masters in effectively packaging themselves into the smallest unit possible which normally is no bigger than a hundred nanometers. Despite their simplicity in structure, their mechanisms of taking advantage of their hosts are sophisticated. Once they have entered the host cell, they are capable of replicating by using the required components from their host.

An Ebolavirus, for example, replicates at an alarming rate, releasing thousands of new viruses until the invaded cell dies. It contains an RNA genome surrounded by a protective coat. This coat surrounding the viral genetic information has become the main target for research.

By finding molecules which are able to bind to the coat, the coat structure can be changed in a way that makes it impossible for the virus to either enter the cell or carry out its replication process after having invaded the host cell. Many molecules capable of binding to the viral coat have been identified but they only bind to the coat after the virus has entered the host cell. In order to ensure that no viral replication has occurred, it is however necessary to prevent the entry of the virus.

The two scientists Warburg and Rong were now lucky to identify one out of 230 screened molecules with this desired ability. They used a modified, and therefore less virulent, type of virus whose coat is identical to the Ebola coat. Interestingly, the molecule which belongs to the isoxazole family not only binds effectively to the Ebola but the Marburg virus suggesting that both types of viruses share a common mechanism of invading the human host cell.

Warburg and Rong expect that their findings will encourage other scientists to find answers to questions how Ebola and Marburg viruses manage to enter the human cell on a molecular basis and whether the identified molecule works in the same way in animal organisms. Doubtlessly, these findings represent a milestone in virology research as they have for the first time shown that Ebola and Marburg virus entry into the cell can be prevented.

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