Antiviral Potential of Sea Urchin Aminated Spinochromes against Herpes Simplex Virus Type 1

Abstract

Herpes simplex virus type 1 (HSV-1) is one of the most prevalent pathogens worldwide requiring the search for new candidates for the creation of antiherpetic drugs. The ability of sea urchin spinochromes—echinochrome A (EchA) and its aminated analogues, echinamines A (EamA) and B (EamB)—to inhibit different stages of HSV-1 infection in Vero cells and to reduce the virus-induced production of reactive oxygen species (ROS) was studied. We found that spinochromes exhibited maximum antiviral activity when HSV-1 was pretreated with these compounds, which indicated the direct effect of spinochromes on HSV-1 particles. EamB and EamA both showed the highest virucidal activity by inhibiting the HSV-1 plaque formation, with a selectivity index (SI) of 80.6 and 50.3, respectively, and a reduction in HSV-1 attachment to cells (SI of 8.5 and 5.8, respectively). EamA and EamB considerably suppressed the early induction of ROS due to the virus infection. The ability of the tested compounds to directly bind to the surface glycoprotein, gD, of HSV-1 was established in silico. The dock score of EchA, EamA, and EamB was −4.75, −5.09, and −5.19 kcal/mol, respectively, which correlated with the SI of the virucidal action of these compounds and explained their ability to suppress the attachment and penetration of the virus into the cells.

Spinochrome Identification and Quantification in Pacific Sea Urchin Shells, Coelomic Fluid and Eggs Using HPLC-DAD-MS

“…Spinochromes, the quinonoid pigments of sea urchins, are known for their diverse pharmacological effects: antioxidant [ 8 , 9 , 10 , 11 ], antimicrobial [ 12 , 13 ], antiviral [ 14 ], cardioprotective [ 15 ], neuroprotective, among others [ 16 , 17 , 18 ]. Despite numerous biochemical studies of spinochromes and examples of their use in medicinal practice, the physiological functions of these compounds in sea urchins are far from understood.…”

Influence of the Structural Features of Carrageenans from Red Algae of the Far Eastern Seas on Their Antiviral Properties

“…The interaction of the HSV-1 surface glycoprotein gD protein with the cellular receptors (nectin-1, 3-O-sulphated heparan sulphate (3-OS HS) and HVEM) triggers the adhesion of the virus to the cell and fusion with the cell membrane [44,45]. The putative binding site for 3-OS-HS of the glycoprotein gD HSV-1 was used for molecular docking of tetrasaccharides [46]. Virucidal compounds may affect gD protein and that inhibit the initial stages of HSV-1 infection.…”

Multifaceted Clinical Effects of Echinochrome

“…Second, Ech A has the ethyl side chain that makes the molecule lipophilic and able to enter membranous structures. Due to these structural features Ech A also become ionizable under physiological conditions and forms eight possible protomeric structures [ 81 ]. Most likely that such a variety of strong effects is explained exactly by the unicity of the structure of Ech A.…”