4.6 Article

The Bovine Seminal Plasma Protein PDC-109 Possesses Pan-Antiviral Activity

Journal

VIRUSES-BASEL
Volume 14, Issue 9, Pages -

Publisher

MDPI
DOI: 10.3390/v14092031

Keywords

SARS-CoV-2; VSV replicon; PDC-109; Bovine seminal plasma; Fn-type 2 proteins

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Funding

  1. Open Access Publication Fund of the University of Duisburg-Essen

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Mammalian seminal plasma contains various bioactive components that play important roles in fertilization. The seminal plasma protein PDC-109 not only affects sperm function but also exhibits antimicrobial and antiviral activity, potentially limiting the sexual transmission of infectious diseases. Recent research has found that PDC-109 inhibits the membrane fusion activity of influenza virus particles and significantly impairs viral infections, including SARS-CoV-2. These findings suggest that PDC-109 has broad antiviral activity against multiple virus species and families.
Mammalian seminal plasma contains a multitude of bioactive components, including lipids, glucose, mineral elements, metabolites, proteins, cytokines, and growth factors, with various functions during insemination and fertilization. The seminal plasma protein PDC-109 is one of the major soluble components of the bovine ejaculate and is crucially important for sperm motility, capacitation, and acrosome reaction. A hitherto underappreciated function of seminal plasma is its anti-microbial and antiviral activity, which may limit the sexual transmission of infectious diseases during intercourse. We have recently discovered that PDC-109 inhibits the membrane fusion activity of influenza virus particles and significantly impairs viral infections at micromolar concentrations. Here we investigated whether the antiviral activity of PDC-109 is restricted to Influenza or if other mammalian viruses are similarly affected. We focused on Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), the etiological agent of the Coronavirus Disease 19 (COVID-19), thoroughly assessing PDC-109 inhibition with SARS-CoV-2 Spike (S)-pseudotyped reporter virus particles, but also live-virus infections. Consistent with our previous publications, we found significant virus inhibition, albeit accompanied by substantial cytotoxicity. However, using time-of-addition experiments we discovered a treatment regimen that enables virus suppression without affecting cell viability. We furthermore demonstrated that PDC-109 is also able to impair infections mediated by the VSV glycoprotein (VSVg), thus indicating a broad pan-antiviral activity against multiple virus species and families.

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