In vitro Inhibition of HIV-1 by Cyclotide-Enriched Extracts of Viola tricolor

Abstract

Since viral infectious diseases continue to be a global health threat, new antiviral drugs are urgently needed. A unique class of therapeutic compounds are antimicrobial peptides (AMPs). They can be found in humans, bacteria and plants. Plants express a wide variety of such defense peptides as part of their innate immune system to protect from invading pathogens. Cyclotides are non-classical AMPs that share a similar structure. Their unique topology consists of a circular peptide backbone and disulfide bonds. In previous studies they have been attributed to a wide range of biological activities. To identify novel cyclotides with antiviral activity, we established a library of plant extracts largely consisting of cyclotide-rich species and screened them as inhibitors of HIV-1 infection. Subsequent extraction and fractionation revealed four cyclotide-containing subfractions from Viola tricolor with antiviral activity. These subfractions inhibited HIV-1 infection with IC50 values between 0.6 and 11.2 μg/ml, and selectivity indices of up to 8.1. The identification and characterization of antiviral cyclotides and the determination of the antiviral mechanisms may allow to develop novel agents to combat viral infections. Therefore, cyclotides represent a natural source of bioactive molecules with prospects for development as therapeutics.

Discovery and development of macrocyclic peptide modulators of the cannabinoid 2 receptor

“…Driven by the concept of nature-derived peptides as source for identification of new chemical scaffolds to modulate GPCR signaling ( 9 , 18 ), we prepared a peptide-enriched plant extract library comprising nine plant species previously recognized to express a suite of cysteine-rich peptides. This included cyclotides from Carapichea ipecacuanha , Palicourea tomentosa , V. odorata , and Viola tricolor ( 27 , 28 ), knottin-like peptides from Bryonia alba ( 29 ), Salix alba , and Strophanthus kombe , as well as short protease inhibitor-like peptides from Helianthus annuus ( 30 ) and Citrus limon . Using chemical solvent and solid phase extraction, we generated a diverse library containing myriad of unknown or previously identified peptides and documented their mass signals in the range of 2500 to 4000 Da with MALDI-TOF mass spectrometry (MS) analysis ( Fig.…”

Discovery and development of macrocyclic peptide modulators of the cannabinoid 2 receptor

“…Driven by the concept of nature-derived peptides as source for identification of new chemical scaffolds to modulate GPCR signaling 8,17 we prepared a peptide-enriched plant extract library comprising nine plant species previously recognized to express a suite of cysteine-rich peptides. This included cyclotides from Carapichea ipecacuanha, Palicourea tomentosa, Viola odorata, and Viola tricolor 26,27 , knottin-like peptides from Bryonia alba 28 , Salix alba and Strophanthus kombe, as well as short protease inhibitor-like peptides from Helianthus annuus 29 and Citrus limon. Using chemical solvent and solid phase extraction, we generated a diverse library containing myriad of unknown or previously identified peptides and documented their mass signals in the range of 2,500-4,000 Da with matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) analysis (Supplementary Fig.…”

Exploring Immune Modulatory Effects of Cyclotide-Enriched Viola tricolor Preparations

“…Viola tricolor L. (Violaceae), also known as wild pansy or heartsease, is a medicinal plant documented in the Pharmacopoeia of Europe. Several biological activities have been attributed to V. tricolor extracts or isolated compounds, including antioxidant, antitumor, cytotoxic, antimicrobial, immunosuppressive, and anti-HIV activities 1 , 2 .…”