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Schematic model of DENV replication based on our results coupling with earlier studies. We propose that the structural rearrangements in both polymerase and the 3′ end region of genomic RNA upon binding of RdRp to the 3′-SL-TL and genomic cyclization play key roles in regulation of viral replication cycle. Accurate mechanisms for recruitment of the 3′ end into the active site of RdRp as well as recognition of the negative stranded genome by RdRp still remain elusive.
