Commonly used antibiotic shows promise for combating Zika virus

2020

Challenge

Zika virus, which is primarily transmitted through the bite of an infected Aedes aegypti mosquito, emerged as a global public health emergency in 2015. The virus has been linked to severe birth defects, including brain abnormalities and microcephaly — underdevelopment of the head and brain — in children, as well as a variety of neurological disorders in adults. Currently, there is no specific treatment for the Zika virus.

Advance

Successful Zika infection depends largely on a protein that permits the virus to multiply in the body. IRP researchers led by Rachel Abrams, Ph.D., Avindra Nath, M.D., and Anton Simeonov, Ph.D., tested a library of 10,000 small molecules to find one that could inhibit this protein. When the research team tested potential inhibitors, they determined that the antibiotic tetracycline and related compounds could inhibit the virus. In mouse models, methacycline, the most potent member of the tetracycline family of antibiotics, reduced the amount of Zika virus present in the brain and lessened neurological damage caused by the virus.

Impact

Since tetracycline antibiotics have already been approved by the U.S. Food and Drug Administration, these drugs could be quickly translated to the clinic and deployed to treat the neurological complications of Zika infection. These common antibiotics also have the potential to be used as preventive medications when traveling to regions where the Zika virus is commonly found.

Publications

Abrams RPM, Yasgar A, Teramoto T, Hwa Lee M, Dorjsuren D, Eastman ET, Malik N, Zakharov AV, Li W, Bachani M, Brimacombe K, Steiner JP, Hall MD, Balasubramanian A, Jadhav A, Radmanabhan R, Simeonov A, Nath A. (2020). Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors. Proc Natl Acad Sci U S A. Dec 8;117(49):31365-31375. doi: 10.1073/pnas.2005463117.