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Open AccessArticle

An Engineered Microvirin Variant with Identical Structural Domains Potently Inhibits Human Immunodeficiency Virus and Hepatitis C Virus Cellular Entry

1
Department of Biology, Syed Babar Ali School of Science and Engineering, Lahore University of Management Sciences, Lahore 54792, Pakistan
2
Applied Molecular Virology Laboratory, Discovery Biology Division, Institut Pasteur Korea, 696, Seongnam 13488, Korea
3
Division of Bio-Medical Science and Technology, University of Science and Technology, Daejeon 34141, Korea
*
Author to whom correspondence should be addressed.
These authors contribute equally to this work.
Viruses 2020, 12(2), 199; https://doi.org/10.3390/v12020199
Received: 13 January 2020 / Accepted: 22 January 2020 / Published: 11 February 2020
(This article belongs to the Special Issue Antiviral Agents)
Microvirin (MVN) is one of the human immunodeficiency virus (HIV-1) entry inhibitor lectins, which consists of two structural domains sharing 35% sequence identity and contrary to many other antiviral lectins, it exists as a monomer. In this study, we engineered an MVN variant, LUMS1, consisting of two domains with 100% sequence identity, thereby reducing the chemical heterogeneity, which is a major factor in eliciting immunogenicity. We determined carbohydrate binding of LUMS1 through NMR chemical shift perturbation and tested its anti-HIV activity in single-round infectivity assay and its anti-hepatitis C virus (HCV) activity in three different assays including HCVcc, HCVpp, and replicon assays. We further investigated the effect of LUMS1 on the activation of T helper (Th) and B cells through flow cytometry. LUMS1 showed binding to α(1-2)mannobiose, the minimum glycan epitope of MVN, potently inhibited HIV-1 and HCV with EC50 of 37.2 and 45.3 nM, respectively, and showed negligible cytotoxicity with CC50 > 10 µM against PBMCs, Huh-7.5 and HepG2 cells, and 4.9 µM against TZM-bl cells. LUMS1 did not activate Th cells, and its stimulatory effect on B cells was markedly less as compared to MVN. Together, with these effects, LUMS1 represents a potential candidate for the development of antiviral therapies. View Full-Text
Keywords: microvirin; lectin; human immunodeficiency virus; hepatitis C virus; antiviral inhibitor; non-immunogenic; viral entry; protein drugs; LUMS1 microvirin; lectin; human immunodeficiency virus; hepatitis C virus; antiviral inhibitor; non-immunogenic; viral entry; protein drugs; LUMS1
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MDPI and ACS Style

Shahid, M.; Qadir, A.; Yang, J.; Ahmad, I.; Zahid, H.; Mirza, S.; Windisch, M.P.; Shahzad-ul-Hussan, S. An Engineered Microvirin Variant with Identical Structural Domains Potently Inhibits Human Immunodeficiency Virus and Hepatitis C Virus Cellular Entry. Viruses 2020, 12, 199.

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