(PTFS11-02-23) Antiviral and Immunomodulatory Effect of Pistachio (Pistacia vera L.) Kernels

Objectives: The current study aimed to investigate the potential role in inhibiting the entry of both HSV-1 and Sars-Cov-2 viruses and the immunomodulatory effect of pistachio kernels on human monocytic cells during HSV-1 replication.

Methods: Polyphenolic extracts from natural raw (NRRE) and roasted unsalted (RURE) pistachio kernels were obtained by two different extraction methods and characterized by RP-HPLC-DAD. The antiviral activity against HSV-1 replication was performed on VERO epithelial cells. THP-1 cells were employed to test the immunomodulatory role of NRRE and RURE by controlling the transcription factor NF-kB. Finally, in order to evaluate the inhibitory effect of NRRE and RURE on SARS-CoV-2, a pseudovirus generated on HEK293T cells was used to test the inhibition of the related luciferase activity.

Results: Both NRRE and RURE exhibited an antiviral effect against HSV-1 through i) partial block of the HSV-1 binding to the cell surface; ii) reduction of viral DNA accumulation and transcripts; iii) modulation of viral proteins expression. Similarly, HSV-1 replication was abrogated by both NRRE and RURE in THP-1 cell lines. In addition, NRRE and RURE downregulated the accumulation of NF-kB transcripts during HSV-1 replication/inflammation. NRRE and RURE exhibited ≥ 50% viral entry inhibition activity at 0.6 mg/mL against SARS-CoV-2.

Conclusions: These data suggest that the antiviral activity of polyphenol-rich extracts from pistachios may be relevant for the formulation of the adjuvant drug against acyclovir-resistant HSV-1 strains and anti-SARS-CoV-2, thus encouraging clinical studies. In the THP-1 cellular model, the control of NF-kB mediated by the pistachio extracts can be relevant as an immunomodulator effect for HSV-1 replication/inflammation.

Funding Sources: The work was funded by American Pistachio Growers (APG, CA, US).