Virucidal Activity of World Health Organization–Recommended Formulations Against Enveloped Viruses, Including Zika, Ebola, and Emerging Coronaviruses

Siddharta, Anindya; Pfaender, Stephanie; Vielle, Nathalie Jane; Dijkman, Ronald; Friesland, Martina; Becker, Britta; Yang, Jaewon; Engelmann, Michael; Todt, Daniel; Windisch, Marc P.; Brill, Florian H.; Steinmann, Joerg; Steinmann, Jochen; Becker, Stephan; Alves, Marco P.; Pietschmann, Thomas; Eickmann, Markus; Thiel, Volker; Steinmann, Eike

Work with infectious EBOV is restricted to biosafety level 4 laboratories, significantly limiting studies with these viruses. In 2014, Watt et al reported a novel life cycle modelling approach for EBOV, which can be performed at biosafety level 2 laboratories [9] . Inactivation of these transcriptionand replication-competent virus-like particles (trVLPs) with WHO formulations showed a dose-dependent reduction of trVLP reporter activity with increasing WHO formulation I and II concentrations ( Figure 2A ). Next, we tested full infectious EBOV cultured at biosafety level 4 for its susceptibility to WHO formulations for potential usage in outbreak situations. Interestingly, viral titers of 10 7 TCID 50 /mL in the control were reduced to background levels at concentrations of 40% with WHO formulation II and 60% with WHO formulation I, showing again a superior virucidal activity of WHO formulation II compared with WHO formulation I ( Figure 2B ). We also included the influenza A virus H1N1 in these inactivation experiments because of its importance in causing viral respiratory epidemics and pandemics. H1N1 could be inactivated at concentrations of 60% with WHO formulation I and 40% with WHO formulation II (Supplementary Figure 1B) . Furthermore, MVA was studied for its susceptibility to WHO formulations because it is the chosen test virus for all enveloped viruses in the European Guideline. In line with EBOV and H1N1, similar inactivation profiles could be observed with increasing WHO formulation I and II concentrations (Supplementary Figure 1C) .