Comparative analyses of small molecule and antibody inhibition on glycoprotein‐mediated entry of Měnglà virus with other filoviruses

Abstract

The ability of viruses in the Filoviridae family (Ebola virus [EBOV] and Marburg virus [MARV]) to cause severe human disease and their pandemic potential makes all emerging filoviral pathogens a concern to humanity. Měnglà virus (MLAV) belonging to the new genus Dianlovirus was recently discovered in the liver of bats from Měnglà County, Yunnan Province, China. The capacity of MLAV to utilize NPC1 as an endosomal receptor, to transduce mammalian cells, and suppress IFN response suggests that this potential pathogen could cause human illness. Despite great effort by researchers, only the viral genome has been recovered and isolation of live MLAV had been unsuccessful. Here using a pseudovirus model baring the MLAV glycoprotein (GP), we studied the protease dependence of the MLAV-GP, and the ability of small molecules and antibodies to inhibit MLAV viral entry. Like EBOV and MARV, the MLAV-GP requires proteolytic processing but like MARV it does not depend on cathepsin B activity for viral entry. Furthermore, previously discovered small-molecule inhibitors and antibodies are MLAV inhibitors and show the possibility of developing these inhibitors as broad-spectrum filovirus antivirals.Overall, the findings in the study confirmed that MLAV viral entry is biologically distinct but has similarities to MARV.

Synthesis and Antiviral Properties of Camphor-Derived Iminothiazolidine-4-Ones and 2,3-Dihydrothiazoles

“…Sertraline was used as a reference substance in this work; this substance is capable of inhibiting the penetration of various filoviruses, presumably at the stage of entry [ 32 ]. The analysis of the biological tests on the activity of compounds against Marburg virus entry shows that the toxicity of compounds on the HEK293FT cell line does not always correlate with the toxicity of compounds on the Vero cell line.…”