Set up of an in vitro platform for the study of the therapeutic potential of helminth molecules against viruses

[Background] Helminth parasites like the trematode Fasciola hepatica, a veterinary parasite with an important zoonotic potential, have adapted to their mammalian hosts during long co-evolution processes by establishing host-parasite relationships that modulate different aspects of the host physiology. In line with this, previous data from our lab showed that F. hepatica newly excysted juveniles (FhNEJ) modulate cellular routes within host cells related to vesiclemediated transport and components of the innate immune response, which could potentially be relevant during the course of viral infections. Therefore, the aim of the present study was to set up an in vitro platform based on the use of viral particles pseudotyped with the envelope protein of highly pathogenic human viruses to screen for the capability of F. hepatica molecules to alter their infective potential.
[Methods] We produced viral particles derived from the vesicular-stomatitis virus (VSV) pseudotyped with Spike, the envelope protein of the recently emerged severe acute respiratory syndrome 2 (SARS-CoV-2), to test for the applicability of this in vitro platform, and validated the results using genuine SARS-CoV-2 infections in Vero cells. Results: Our compound screen revealed that a tegument-enriched antigenic fraction of FhNEJ contains proteins with antiviral potential against both Spike-pseudotyped VSV viral particles and live SARS-CoV-2.
[Conclusions] First, our results revealed that FhNEJ express molecules that are capable of mediating virus entry and/or replication of SARS-CoV-2 virus and potentially other enveloped viruses with zoonotic potential. Second, our results evidenced that the in vitro platform that we established for virus pseudotyping is valid for the interrogation of antiviral molecules from F. hepatica. Altogether, this platform could lead to the identification of antiviral molecules in helminth parasites and encourage their production in a safe, synthetic format for their application as therapeutics against viruses of growing public health concern.