Experiments and simulation on ZIKV NS2B-NS3 protease reveal its complex folding

Highlights: • Folding dynamics of NS2B-NS3 protease of Zika virus. • NS2B-NS3 protease has high structure stability at wide pH range and temperature. • HFIP and TFE induces helix rich secondary structure in NS2B-NS3 protease. • The NS2B-NS3 protease structure is susceptible to malleable folding. Zika virus has been identified in various body fluids such as semen, urine, saliva, cerebrospinal fluid, and vaginal secretion of an infected individual. The pH of these fluids varies from mildly acidic to mildly alkaline. So it is imperative to understand the impact of these conditions on viral protein functioning. We investigated the NS2B-NS3 protease stability and its activity in different denaturing environments. Finding indicates that NS2B-NS3 protease maintains stability at pH 4.8–8.7. Thus it suggests that the complex remains functionally active to hydrolyze the polyprotein within a diverse environmental condition such as variable pH. Despite a stable structure at a broad pH range, a change in environmental conditions dramatically influence its protease activity. Moreover, it is susceptible to structural transformation leading to increased β-strand or helix content in the presence of alcohol. This study may help further to understand the folding-function relationship of the general flaviviral protease complex.