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An Engineered Microvirin Variant with Identical Structural Domains Potently Inhibits Human Immunodeficiency Virus and

Munazza Shahid1, Amina Qadir1, Jaewon Yang2

  • 1Department of Biology, Syed Babar Ali School of Science and Engineering, Lahore University of Management Sciences, Lahore 54792, Pakistan.

Viruses
|February 15, 2020
PubMed

Insights

Engineered microvirin variant LUMS1, with identical domains, potently inhibits HIV-1 and HCV. LUMS1 shows reduced immune cell activation, presenting a promising antiviral therapy candidate.

Area of Science:

  • Virology
  • Immunology
  • Biochemistry

Background:

  • Microvirin (MVN) is a monomeric lectin inhibiting human immunodeficiency virus type 1 (HIV-1) entry.
  • Antiviral lectins can elicit immunogenicity due to chemical heterogeneity.
  • Reducing heterogeneity is key to developing safer antiviral agents.

Purpose of the Study:

  • To engineer a microvirin variant (LUMS1) with reduced immunogenicity by creating identical structural domains.
  • To evaluate LUMS1's carbohydrate binding, antiviral activity against HIV-1 and hepatitis C virus (HCV), and immunomodulatory effects.

Main Methods:

  • Engineered LUMS1 with 100% sequence identity between its two domains.
  • Determined carbohydrate binding using NMR chemical shift perturbation.
  • Assessed anti-HIV and anti-HCV activity via infectivity, HCVcc, HCVpp, and replicon assays.
  • Investigated T helper (Th) and B cell activation using flow cytometry.

Main Results:

  • LUMS1 bound to (1-2)mannobiose, MVN's minimal glycan epitope.
  • LUMS1 potently inhibited HIV-1 (EC50 = 37.2 nM) and HCV (EC50 = 45.3 nM).
  • LUMS1 exhibited low cytotoxicity (CC50 > 10 µM in most cell lines) and significantly less Th and B cell activation compared to MVN.

Conclusions:

  • LUMS1, a homogeneous MVN variant, demonstrates potent broad-spectrum antiviral activity.
  • LUMS1 shows a favorable safety profile with reduced immunomodulatory effects.
  • LUMS1 is a promising candidate for developing novel antiviral therapies against HIV-1 and HCV.
Keywords:
LUMS1antiviral inhibitorhepatitis C virushuman immunodeficiency viruslectinmicrovirinnon-immunogenicprotein drugsviral entry

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