Back to Journals » Virus Adaptation and Treatment » Volume 2

Small molecule inhibitors of the SARS-CoV Nsp15 endoribonuclease

Authors Ortiz-Alcantara J, Bhardwaj K, Palaninathan S, Frieman M, Baric R, Kao C

Published 6 September 2010 Volume 2010:2 Pages 125—133


Review by Single-blind

Peer reviewer comments 3

J Ortiz-Alcantara1, K Bhardwaj2, S Palaninathan1, M Frieman3, RS Baric3, CC Kao2

1Department of Biochemistry and Biophysics, Texas A&M University College Station, TX, USA; 2Department of Molecular Cellular Biochemistry, Indiana University, Bloomington IN, USA; 3Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

Abstract: The severe acute respiratory syndrome (SARS) virus encodes several unusual RNA processing enzymes, including Nsp15, an endoribonuclease that preferentially cleaves 3’ of uridylates through a ribonuclease A (RNase A)-like mechanism. Crystal structures of Nsp15 confirmed that the Nsp15 active site is structurally similar to that of RNase A. These similarities and our molecular docking analysis lead us to hypothesize that previously characterized RNase A inhibitors will also inhibit the SARS-CoV Nsp15. Benzopurpurin B, C-467929, C-473872, N-306711, N-65828, N-103019 and congo red were tested for effects on Nsp15 endoribonuclease activity. A fluorescence assay revealed that the IC50 values for inhibiting endoribonuclease activity were between 0.2 µM and 40 µM. These compounds were demonstrated to bind SARS-CoV Nsp15 by a differential scanning fluorimetry assay. Benzopurpurin B also inhibited the endoribonuclease activities of the Nsp15 orthologs from two other coronaviruses: mouse hepatitis virus (MHV) and infectious bronchitis virus (IBV). Benzopurpurin B, C-473872, and congo red reduced infectivity of MHV in L2 cells by 8- to 26- fold. The more effective drugs caused a decrease in MHV RNA accumulation. All three compounds reduced the infectivity of the SARS-CoV in Vero cells.

Keywords: SARS, endoribonuclease, small molecule inhibitors

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF] 


Other articles by this author:

Phosphorylation of the viral coat protein regulates RNA virus infection

Hoover HS, Kao CC

Virus Adaptation and Treatment 2016, 8:13-20

Published Date: 24 November 2016

Mapping protein–RNA interactions

Vaughan R, Running W, Qi R, Kao CC

Virus Adaptation and Treatment 2012, 4:29-41

Published Date: 2 May 2012

Conformations of the monomeric hepatitis C virus RNA-dependent RNA polymerase

Sreedhar Chinnaswamy, Ayaluru Murali, Hui Cai, et al

Virus Adaptation and Treatment 2010, 2:21-39

Published Date: 11 March 2010

Readers of this article also read:

Green synthesis of water-soluble nontoxic polymeric nanocomposites containing silver nanoparticles

Prozorova GF, Pozdnyakov AS, Kuznetsova NP, Korzhova SA, Emel’yanov AI, Ermakova TG, Fadeeva TV, Sosedova LM

International Journal of Nanomedicine 2014, 9:1883-1889

Published Date: 16 April 2014

Methacrylic-based nanogels for the pH-sensitive delivery of 5-Fluorouracil in the colon

Ashwanikumar N, Kumar NA, Nair SA, Kumar GS

International Journal of Nanomedicine 2012, 7:5769-5779

Published Date: 15 November 2012

A novel preparation method for silicone oil nanoemulsions and its application for coating hair with silicone

Hu Z, Liao M, Chen Y, Cai Y, Meng L, Liu Y, Lv N, Liu Z, Yuan W

International Journal of Nanomedicine 2012, 7:5719-5724

Published Date: 12 November 2012

Cross-linked acrylic hydrogel for the controlled delivery of hydrophobic drugs in cancer therapy

Deepa G, Thulasidasan AK, Anto RJ, Pillai JJ, Kumar GS

International Journal of Nanomedicine 2012, 7:4077-4088

Published Date: 27 July 2012

Crystallization after intravitreal ganciclovir injection

Pitipol Choopong, Nattaporn Tesavibul, Nattawut Rodanant

Clinical Ophthalmology 2010, 4:709-711

Published Date: 14 July 2010