Myricetin antagonizes semen-derived enhancer of viral infection (SEVI) formation and influences its infection-enhancing activity

Abstract

BackgroundSemen is a critical vector for human immunodeficiency virus (HIV) sexual transmission and harbors seminal amyloid fibrils that can markedly enhance HIV infection. Semen-derived enhancer of viral infection (SEVI) is one of the best-characterized seminal amyloid fibrils. Due to their highly cationic properties, SEVI fibrils can capture HIV virions, increase viral attachment to target cells, and augment viral fusion. Some studies have reported that myricetin antagonizes amyloid β-protein (Aβ) formation; myricetin also displays strong anti-HIV activity in vitro.ResultsHere, we report that myricetin inhibits the formation of SEVI fibrils by binding to the amyloidogenic region of the SEVI precursor peptide (PAP248–286) and disrupting PAP248–286 oligomerization. In addition, myricetin was found to remodel preformed SEVI fibrils and to influence the activity of SEVI in promoting HIV-1 infection. Moreover, myricetin showed synergistic effects against HIV-1 infection in combination with other antiretroviral drugs in semen.ConclusionsIncorporation of myricetin into a combination bifunctional microbicide with both anti-SEVI and anti-HIV activities is a highly promising approach to preventing sexual transmission of HIV.Electronic supplementary materialThe online version of this article (10.1186/s12977-018-0432-3) contains supplementary material, which is available to authorized users.

Nanoparticle-Based Immunoengineered Approaches for Combating HIV

“…Another approach utilized semen-derived enhancer of viral infection (SEVI), which is a type of amyloid fibril present in human semen that enhances HIV-1 infection of target cells by capturing HIV-1 virions, resulting in increased viral fusion (84). SEVI serves as a mediator for HIV-1 viral attachment due to its highly cationic nature (84,85). In their study, Sheik et al, synthesized a hydrophobic polymeric nanoparticle to reduce SEVI fibril-mediated infection (58).…”

Ultra-small micelles based on polyoxyl 15 hydroxystearate for ocular delivery of myricetin: optimization, in vitro, and in vivo evaluation

“…Bioactive compounds from plant sources, generally categorized as natural antioxidants, have attracted increased attention for their health-promoting characteristics including anti-inflammatory and neuroprotective effects, as well as, free radical scavenging (Al-Juhaimi et al., 2018). Myricetin (Myr) is a naturally occurring flavonoid commonly found in medicinal herbs, vegetables, fruits, and tea, and it has been found to display a wide variety of biological activities such as antioxidant and anti-inflammatory effects (Ren et al., 2018). Myr was shown to function as a potent and effective neuroprotective agent for photoreceptor cells against A2E and light damage, mainly via its antioxidative activity (Laabich et al., 2007).…”

Emergence of Nanotechnology to Fight HIV Sexual Transmission: The Trip of G2-S16 Polyanionic Carbosilane Dendrimer to Possible Pre-Clinical Trials

“…These SEVI capture HIV virions, thus, promoting their adhesion to target cells and increasing their ability to infect human cells, regardless of the cell type involved [ 43 , 44 , 45 ]. Reports specify that exposure of HIV particles to a concentration of 10% semen increases HIV infectivity up to 10-fold, and also shortens the exposure time to microbicides acting outside of the cell, which aim to avoid virus entry by impeding accessibility to virus membrane and glycoproteins [ 41 , 45 , 46 , 47 , 48 ]. This might explain why many microbicides that show high efficacy in vitro fail to be effective in clinical trials, and thereby, no commercially topical microbicide is available yet [ 49 ].…”