Researchers at the University of Texas Medical Branch at Galveston have uncovered a new antiviral mechanism for the new dengue virus.
Findings were published in Proceedings of the National Academy of Sciences.
The dengue virus is a mosquito-transmitted pathogen leading to 390 million human infections annually. The virus is prevalent in more than 100 countries with about forty percent of the global population at risk of infection. Symptoms of the dengue virus infection can range from mild to severe. To this present day, there has not been any clinically proven drugs, such as inhibitors, to target the virus activity.
"There are four types of dengue virus, all of which can cause epidemics and disease in humans. The current inhibitor does not inhibit all types of dengue virus. Our co-crystal structure explains why this is the case," said Pei-Yong Shi, I.H. Kempner professor of Human Genetics at UTMB. "Using this new information, we will be able to design new drugs that can inhibit all types of dengue virus. In addition, the structural information will also enable us to make compounds with improved potency and drug-like properties."
Researchers were able to determine the structure of the dengue capsid protein and from there detail how an inhibitor can bind and thwart its normal function.
"The inhibitor binds four capsid molecules to form a tetramer. Such capsid tetramers are assembled into dengue virus," said Mark White, Associate Professor at UTMB who co-senior authored the study. "However, such a tetramer-containing virus is not able to productively infect new cells. Our study also explains how resistance emerges when dengue virus is treated with the inhibitor. A resistant virus emerges through one amino acid change that weakens the compound binding to the viral capsid protein."
Learn more about the dengue virus:
"The World Health Organization lists dengue virus as one of the top ten public health threats and as such requires the urgent development of effective vaccine and therapeutics," said Hongjie Xia, UTMB postdoctoral fellow and lead author of the study. "Although we are currently coping with COVID-19 pandemic, Singapore and other regions are experiencing a record number of dengue human cases. This motivates our team to develop clinical treatments for this devastating disease."
Source: Science Daily
