Suppression of Drug Resistance in Dengue Virus

摘要: ABSTRACT Dengue virus is a major human pathogen responsible for 400 million infections yearly. As with other RNA viruses, daunting challenges to antiviral design exist due the high error rates of RNA-dependent synthesis. Indeed, treatment dengue infection nucleoside analog resulted in expected genetic selection resistant viruses tissue culture and mice. However, when function oligomeric core protein was inhibited, no detectable drug resistance or mice detected, despite presence drug-resistant variants population. Suppressed correlated cooligomerization targeted drug-susceptible proteins. The concept “dominant targets,” which inhibition viral assemblages leads formation chimeras, can therefore be used prevent outgrowth during infection. IMPORTANCE Drug hurdle development effective antivirals, especially those directed at viruses. We have found that one use dominance defective subunits “turn cousins into enemies,” i.e., thwart genomes as soon they are generated. This requires deliberate targeting larger assemblages, would otherwise rarely considered by researchers.