Anti-HSV-1 activity of Aspergillipeptide D, a cyclic pentapeptide isolated from fungus Aspergillus sp. SCSIO 41501

Abstract

Background: Herpes simplex virus 1, an enveloped DNA virus belonging to the Herpesviridae family, spreads to neurons and causes pathological changes in the central nervous system. The purpose of this study was to investigate the potency and mechanism of antiviral activity of Aspergillipeptide D, a cyclic pentapeptide isolated from a culture broth of marine gorgonian-derived fungus Aspergillus sp. SCSIO 41501, At present, there are many studies on the anti-tumor, anti-clotting, anti-oxidant and immunoinflammatory effects of Aspergillipeptide D, but little research has been done on the anti-HSV-1 activity of Aspergillipeptide D. Methods: The anti-HSV-1 activity of Aspergillipeptide D was evaluated by plaque reduction assay. The mechanism of action against HSV-1 was determined from the effective stage. Then we assayed the viral DNA replication, viral RNA synthesis and protein expression, respectively. We also identified the proteins that interact with gB by mass spectrometry, and assayed the effect of Aspergillipeptide D on the interaction between the virus gB protein and cell proteins. Results: Plaque reduction experiments showed that Aspergillipeptide D did not affect HSV-1 early infection events, including viral inactivation, attachment and penetration. Interestingly, Aspergillipeptide D dramatically reduced both the gene and protein levels of viral late protein gB, and suppressed its location in the endoplasmic reticulum and Golgi apparatus. In contrast, overexpression of gB restored viral production. Finally, proteomic analysis revealed that the numbers of cellular proteins that interacted with gB protein was largely decreased by Aspergillipeptide D. These results suggested that Aspergillipeptide D inhibited gB function to affect HSV-1 intercellular spread. Conclusions: Our results indicated that Aspergillipeptide D might be a potential candidate for HSV-1 therapy, especially for ACV-resistant strains.

Three New Metabolites From the Marine-Derived Fungus Aspergillus sp. WHUF03110

“…In conclusion, twelve compounds, including three new compounds (1-3), and nine known compounds (4)(5)(6)(7)(8)(9)(10)(11)(12) were isolated by fractionation of the EtOAc extract prepared from a rice fermentation culture of Aspergillus sp. WHUF03110.…”

Structure-Function Characteristics of SARS-CoV-2 Proteases and Their Potential Inhibitors from Microbial Sources

“…As shown in Table 1, the promising compounds for 3CLpro-CoV2 or PLpro-CoV2 inhibitors are dominated from Aspergillus groups. Antiviral activity of Aspergillus groups against some viruses are widely reported [102][103][104][105], nevertheless no report for experimental evidence on the antiviral properties of this group against living SARS-CoV-2 exists. Interestingly, Koehler et al [106] reported that COVID-19 patients are more susceptible towards invasive pulmonary aspergillosis (IPA).…”

An Updated Overview of Herpes Simplex Virus-1 Infection: Insights from Origin to Mitigation Measures

“…Further, a compound name apigenin is found to create obstacles in the cell to cell virus spread [153]. Research on Aspergillipeptide D revealed that though it doesn't interrupt in HSV-1 viral infection stages but dramatically it reduces both gene and protein levels including viral late protein gB and found to suppress its location on endoplasmic reticulum and Golgi apparatus [154]. Besides, Omeprazole was found to increase the anti-cancer effect of nucleoside analog 5-fluorouracil without affecting ribavirin in nontoxic concentration (up to 80 mg/mL).…”