Structure-based drug design for Dengue Virus Non-Structural Protein 3

BOLLINI, MARIELA; SARTO, CAROLINA; ARRAR, MEHRNOOSH; ADLER, NATALIA

Congreso; LatinXChem Twitter Conference 2020; 2020

Dengue represents a substantial public health burden. Non-structural protein 3 (NS3) is a multifunctional protein critical in the virus life cycle that has been identified as a promising anti-viral drug target.1DENV NS3 helicase domain (NS3hel) couples ATPase and helicase activities. Even though the details of this mechanism remains unclear, in our previous work we identified structural nucleotide-dependent differences.2 During the infection, NS3hel interacts with NS5, the viral 5´-RNA methyltransferase/polymerase, via specific residues which were experimentally determined using site-directed mutagenesis and competitive binding assays. Moreover, the ASN570 of the NS3hel is proposed to be essential for the PPI and the NS3N570A mutation, to reduce infectious virus production 3. We use molecular dynamics simulations of NS3hel to examine the residues involved in the NS3hel-NS5 interaction and propose a structure-based drug design approach.