A scorpion venom peptide Ev37 restricts viral late entry by alkalizing acidic organelles

Abstract

Viral infections still threaten human health all over the world, and many people die from viral diseases every year. However, there are no effective vaccines or drugs for preventing or managing most viral diseases. Thus, the discovery and development of broad-spectrum antiviral agents remain urgent. Here, we expressed and purified a venom peptide, Ev37, from the scorpion Euscorpiops validus in a prokaryotic system. We found that rEv37 can inhibit dengue virus type 2 (DENV-2), hepatitis C virus (HCV), Zika virus (ZIKV), and herpes simplex virus type 1 (HSV-1) infections in a dose-dependent manner at noncytotoxic concentrations, but that it has no effect on Sendai virus (SeV) and adenovirus (AdV) infections in vitro. Furthermore, rEv37 alkalized acidic organelles to prevent low pH-dependent fusion of the viral membrane-endosomal membrane, which mainly blocks the release of the viral genome from the endosome to the cytoplasm and then restricts viral late entry. Taken together, our results indicate that the scorpion venom peptide Ev37 is a broad-spectrum antiviral agent with a specific molecular mechanism against viruses undergoing low pH-dependent fusion activation during entry into host cells. We conclude that Ev37 is a potential candidate for development as an antiviral drug.

Topology, Antiviral Functional Residues and Mechanism of IFITM1

“…The cDNA was quantitated by qPCR with SeV and GAPDH primers using the Bestar ® SYBR Green qPCR master mix reagent (DBI ® Bioscience, Shanghai, China). The primers of ZIKV, SeV Viruses 2020, 12, 295 4 of 14 and GAPDH were synthesized as our laboratory previously described [18]. qPCR experiments were performed on an ABI 7500 system (Shanghai, China) according to the instructions.…”

A broad-spectrum virus- and host-targeting peptide against respiratory viruses including influenza virus and SARS-CoV-2

“…We have also reported different types of antiviral peptides which inhibit influenza virus by delivering defective interfering gene 14 , zika virus by targeting envelope protein 15 , MERS-CoV by blocking viral fusion 16 . Other groups have reported the broad-spectrum antiviral peptide BanLec which inhibits HIV, hepatitis C virus (HCV) and influenza virus 17 , the theta-defensin retrocylin 2, which inhibits influenza virus, Sindbis virus, and baculovirus 18 , the typical cationic and amphipathic tetradecapeptide mastoparan which inhibits enveloped viruses 19 , two scorpion venom peptide variants including mucroporin-M1 which inhibits measles, SARS-CoV and H5N1 virus 20 , and the Ev37 which inhibits dengue virus, HCV, zika virus, and herpes simplex virus 21 , and other host defense peptides which inhibit different enveloped and non-enveloped viruses with documented or unknown mechanism 22 – 24 . Since the first anti-HIV peptide enfuvirtide was approved by FDA for the treatment of HIV in 2003 25 , other peptides with antiviral activity have been approved by FDA 26 .…”

Doratoxylon apetalum, an Indigenous Medicinal Plant from Mascarene Islands, Is a Potent Inhibitor of Zika and Dengue Virus Infection in Human Cells

“…While D. apetalum extract could inactivate the ZIKV particles, we do not believe that a direct lysis effect of the viral membrane is responsible for their effects, since ZIKV attachment to the cell membrane can occur with D. apetalum . Future experiments using confocal microscopy will be undertaken to validate our assumption that D. apetalum -mediated ZIKV inhibition essentially relates to a lack of virus internalisation into the host cell [38].…”