Identification of Inhibitors of Chikungunya virus nsP2 ATPase

Hernan Navarro; John E Scott; Ginger R Smith; Pegah Ghiabi; Elisa Gibson; Peter Loppnau; Rachel J Harding; Mohammad Anwar Hossain; Muthu Ramalingam Bose; Kenneth H Pearce; Eric M Merten; Timothy M Willson; Peter J Brown

doi:10.1101/2024.12.02.625520

Identification of Inhibitors of Chikungunya virus nsP2 ATPase

bioRxiv [Preprint]. 2024 Dec 6:2024.12.02.625520. doi: 10.1101/2024.12.02.625520.

Authors

Hernan Navarro^{1

2}, John E Scott^{1

2}, Ginger R Smith^{1

2}, Pegah Ghiabi^{3

2}, Elisa Gibson^{3

2}, Peter Loppnau^{3

2}, Rachel J Harding^{3

2}, Mohammad Anwar Hossain^{2

4}, Muthu Ramalingam Bose^{2

4}, Kenneth H Pearce^{2

5}, Eric M Merten^{2

5}, Timothy M Willson^{2

4}, Peter J Brown^{2

4}

Affiliations

¹ Department of Pharmaceutical Sciences, Biomanufacturing Research Institute and Technology Enterprise (BRITE), North Carolina Central University, Durham, NC 27707, USA.
² READDI AViDD Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
³ Structural Genomics Consortium, University of Toronto, Toronto, Ontario, M5G 1L7, Canada.
⁴ Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁵ UNC Eshelman School of Pharmacy, Center for Integrative Chemical Biology and Drug Discovery, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Abstract

Non-structural protein 2 (nsP2), which plays an essential role in replication of CHIKV, contains a protease, helicase, and methyltransferase-like domain. We executed a simple a screen using malachite green to detect compounds that decreased ATP hydrolysis and tested a library of diverse compounds to find inhibitors of CHIKV nsP2 helicase.

Publication types

Preprint

Grants and funding

U19 AI171292/AI/NIAID NIH HHS/United States