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

Retrovirology
Ruxia RenLin Li

Abstract

Semen 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. Here, 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. Incorporation 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.

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Citations

Mar 3, 2019·European Journal of Drug Metabolism and Pharmacokinetics·Dan LouJia-Yang He
May 20, 2020·Frontiers in Immunology·Allan BowenRohan Fernandes
Jan 7, 2020·Journal of Nutritional Science and Vitaminology·Lu WangWenbin Dong
Dec 19, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Xiaominting SongJin Pei
Dec 17, 2020·International Journal of Molecular Sciences·Ignacio Relaño-Rodríguez, Maria Ángeles Muñoz-Fernández

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Methods Mentioned

BETA
transmission electron microscopy
circular dichroism
surface plasmon resonance
chip
flow cytometry
fluorescence microscopy
pull-down
ELISA
confocal microscopy
electrophoresis

Software Mentioned

BIAcore
GraphPad Prism
UCSF Chimera
AutoDock
PyMOL
Protein
PICUP
CalcuSyn
– Ligand Interaction Profiler

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