The Scorpion Venom Peptide Smp76 Inhibits Viral Infection by Regulating Type-I Interferon Response

Abstract

Dengue virus (DENV) and Zika virus (ZIKV) have spread throughout many countries in the developing world and infect millions of people every year, causing severe harm to human health and the economy. Unfortunately, there are few effective vaccines and therapies available against these viruses. Therefore, the discovery of new antiviral agents is critical. Herein, a scorpion venom peptide (Smp76) characterized from Scorpio maurus palmatus was successfully expressed and purified in Escherichia coli BL21(DE3). The recombinant Smp76 (rSmp76) was found to effectively inhibit DENV and ZIKV infections in a dose-dependent manner in both cultured cell lines and primary mouse macrophages. Interestingly, rSmp76 did not inactivate the viral particles directly but suppressed the established viral infection, similar to the effect of interferon (IFN)-b. Mechanistically, rSmp76 was revealed to upregulate the expression of IFN-b by activating interferon regulatory transcription factor 3 (IRF3) phosphorylation, enhancing the type-I IFN response and inhibiting viral infection. This mechanism is significantly different from traditional virucidal antimicrobial peptides (AMPs). Overall, the scorpion venom peptide Smp76 is a potential new antiviral agent with a unique mechanism involving type-I IFN responses, demonstrating that natural AMPs can enhance immunity by functioning as immunomodulators. Keywords Dengue virus (DENV) Á Zika virus (ZIKV) Á Scorpion venom peptide Á Smp76 Á Antiviral mechanism Á Type-I interferon response Electronic supplementary material The online version of this article (

Scorpion-Derived Antiviral Peptides with a Special Focus on Medically Important Viruses: An Update

“…The virus particles are spherical and small in size, with an envelope protein and membrane proteins. It causes microcephaly and Guillain-Barre syndrome [ 45 ].…”

“…rSmp76 is able to inactivate established infection effectively with an IC 50 of 6.63 μ mol/l. rSmp76 suppresses the established infection of ZIKV by triggering interferon regulatory transcription factor 3 phosphorylation, leading to the upregulation of IFN- β expression and inhibition of viral infection [ 45 , 47 ].…”

Scorpion Venom: Detriments and Benefits

“…Although the detailed molecular mechanisms of the rSmp76-induced inhibitory effects need to be elucidated, it seems that the mechanism of inhibition did not include direct inactivation of the viral particles. It has been suggested that rSmp76 suppresses an established viral infection by upregulating interferon-β expression through the phosphorylation of the interferon regulatory factor 3, which enhances type-I IFN responses and thus inhibits viral infection [131]. Since the achievement of viral clearance is very difficult, antiviral agents, such as rSmp76, that can suppress established viral infections are considered to be more efficient than traditional antiviral therapeutics, which exert their antiviral effects through the direct inactivation of viral particles or the inhibition of viral cell entry [131].…”

Smp76, a Scorpine-Like Peptide Isolated from the Venom of the Scorpion Scorpio maurus palmatus, with a Potent Antiviral Activity Against Hepatitis C Virus and Dengue Virus

“…Interestingly, the recombinant Smp76 was shown to inhibit DENV and ZIKV infections in cultured cell lines and primary mouse macrophages. However, rSmp76 did not inactivate the viral particles directly but suppressed the established viral infection by upregulating the expression of IFN-β (Ji et al 2018). This mechanism is significantly different from the virucidal effect of native Smp76 peptides.…”