Focus on the Flu
Fighting Back: New Drugs against Flu
The traditional advice for treating flu—bed rest and fluids—works quite well in most cases. For the elderly, the very young and people with chronic illness, however, flu and its complications can be life-threatening. While several drugs exist to treat flu, they must be taken within 48 hours of the start of the illness. NIAID grantees, including Jianzhu Chen, Ph.D., and Mang Yu, Ph.D., are exploring ways some futuristic technologies might lead to better flu drugs.
A Welcome Interference
RNA interference (RNAi) is a cellular phenomenon that scientists are just now starting to understand and exploit. Jianzhu Chen, Ph.D., and his colleagues at the Massachusetts Institute of Technology are exploring the possibility of using RNAi to hinder flu's ability to multiply inside the cells it attacks. RNAi can selectively inhibit gene activity in cells. Essentially, the technique allows researchers to turn individual genes "off." Dr. Chen and his team have experimented with a particular form of RNAi, called short interfering RNA (siRNA), specific for genes that flu virus requires to reproduce inside human cells.
In laboratory-grown cells and chicken embryos, the siRNAs exhibited a powerful effect on the virus' ability to make new copies of itself. Moreover, the tested siRNAs worked even at extremely small amounts, opening the possibility that they might prevent the flu virus from gaining a foothold and turning into full-blown disease. Also, as the researchers note in a recent scientific paper, siRNAs are attractive as potential flu preventives or drugs because they could be given through the nose and upper respiratory tract where flu first enters the body.
A recent paper by Dr. Chen and his colleagues is: "RNA interference of influenza virus production by directly targeting mRNA for degradation and indirectly inhibiting all viral RNA transcription," in the Proceedings of the National Academy of Sciences.
Seal Off the Entryways
At the biotech company Nexbio in San Diego, CA, NIAID grantee Mang Yu, Ph.D., is pursuing research on a kind of drug called a fusion protein, which might one day guard against multiple flu strains. If successful, not only could such drug become a strong weapon to fight the annual epidemic flu, but it could be on standby in case of an outbreak of pandemic flu.
Before it can cause disease, the flu virus must first enter a human cell. To enter, the virus passes through any one of a variety of gateways (receptors) on the cell's surface. NexBio is developing fusion proteins that target a cellular process that renders cells inaccessible by flu virus particles; therefore, flu particles have no way to initiate the disease process.
Ultimately, Dr. Yu and his colleagues at NexBio want to develop this fusion-protein drug so it can be inhaled or applied topically for both prevention and treatment of flu viral infections.
Although NexBio is taking a novel approach to fight influenza virus, Dr. Yu and his colleagues are veteran drug developers in the field of respiratory viral infections. They have previously used lab-made antibodies to block the entry of human rhinovirus, the cause of the common cold, into cells. Their cold virus research has led to a promising drug candidate, CFY 196, which was described in the paper titled "Viral receptor blockage by multivalent recombinant antibody fusion proteins: inhibiting human rhinovirus (HRV) infection with CFY196," in the Journal of Antimicrobial Chemotherapy."