A multidisciplinary team from The University of Texas Medical Branch (UTMB) at Galveston has uncovered a new mechanism for designing antiviral drugs for the dengue virus. The results of the new study were published online on July 15, 2020 in PNAS. The article is titled “A Cocrystal Structure of Dengue Capsid Protein in Complex of Inhibitor.” Dengue virus is a very important mosquito-transmitted viral pathogen, causing 390 million human infections each year. Dengue is common in more than 100 countries and forty percent of the world's population is at risk of infection. When someone becomes ill with dengue, symptoms that can range from mild to severe may include fever, nausea/vomiting, rash, and muscle/bone/joint aches. Despite this, there are no clinically approved drugs currently available to people who become infected. In this study, the UTMB team has solved the co-crystal structure of the dengue capsid protein, which forms the interior of the virus, in complex with an inhibitor. The co-crystal structure has provided atomic details of how the inhibitor binds the capsid protein and blocks its normal function, leading to the inhibition of viral infection. The structural information has opened new avenues to rationally design inhibitors for antiviral development. "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, PhD, the 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."
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