Work

A 2-Hydroxyisoquinoline-1,3-Dione Active-Site RNase H Inhibitor Binds in Multiple Modes to HIV-1 Reverse Transcriptase

Year: 2017

Type: article

Abstract: ABSTRACT The RNase H (RNH) function of HIV-1 reverse transcriptase (RT) plays an essential part in the viral life cycle. We report the characterization of YLC2-155, a 2-hydroxyisoquinoline-1,3-dione (HID)-based active-site RNH inhibitor. YLC2-155 inhibits both polymerase (50% inhibitory concentration [IC 50 ] = 2.6 μM) and RNH functions (IC 50 = 0.65 μM) of RT but is more effective against RNH. X-ray crystallography, nuclear magnetic resonance (NMR) analysis, and molecular modeling were used to show that YLC2-155 binds at the RNH-active site in multiple conformations.

Source: Antimicrobial Agents and Chemotherapy

DOI: 10.1128/aac.01351-17

Authors: Karen A. Kirby, Nataliya A. Myshakina, Martin T. Christen, Yue-Lei Chen, Hilary A. Schmidt, Andrew D. Huber, Zhaoyong Xi, Seongmi Kim, Rohit K. Rao, Skyler T. Kramer, Qiongying Yang, Kamalendra Singh, Michael A. Parniak, Zhengqiang Wang, Rieko Ishima, Stefan G. Sarafianos

Institutions: University of Missouri, University of Pittsburgh, Chatham University, University of Minnesota

Language: English

Topic: HIV/AIDS drug development and treatment

Subfield: Infectious Diseases

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: National Institutes of Health, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases

Awards: Conformational Dynamics and inhibitor responses of HIV-1 RT RNase H in solution, Acylhydrazone inhibitors of HIV-1 ribonuclease H, Novel antivirals targeting the RNase H activity of HIV reverse transcriptase

OpenAlex ID: W2740835342

FWCI: 1.684

Cites: 32

Cited by: 21

Related to: 10