Lectins as Promising Therapeutics for the Prevention and Treatment of HIV and Other Potential Coinfections.

Milena Mazalovska,J Calvin Kouokam

doi:10.1155/2018/3750646

Abstract

Human immunodeficiency virus-acquired immunodeficiency syndrome (HIV/AIDS) remains a global health problem. Current therapeutics specifically target the viral pathogen at various stages of its life cycle, although complex interactions between HIV and other pathogenic organisms are evident. Targeting HIV and concomitant infectious pathogens simultaneously, both by therapeutic regimens and in prevention strategies, would help contain the AIDS pandemic. Lectins, a ubiquitous group of proteins that specifically bind glycosylated molecules, are interesting compounds that could be used for this purpose, with demonstrated anti-HIV properties. In addition, potential coinfecting pathogens, including other enveloped viruses, bacteria, yeasts and fungi, and protozoa, display sugar-coated macromolecules on their surfaces, making them potential targets of lectins. This review summarizes the currently available findings suggesting that lectins should be further developed to simultaneously fight the AIDS pandemic and concomitant infections in HIV infected individuals.

Highlights

Human immunodeficiency virus (HIV) infection remains a leading public health problem, due to the rapid mutation of the virus, resistance to existing therapies, lack of a vaccine, and inadequate use of physical prophylaxis, for example, resistance to condom use for cultural or religious reasons [1]
Current antiretroviral drugs (ARVs) greatly improve the clinical outcomes of HIV positive individuals and limit disease transmission with improved safety, elevated tolerability, and high potency, especially if used early in the infection [5]
Truvada was the first FDA approved drug for HIV preexposure prophylaxis (PrEP) in an attempt to reduce and prevent HIV infection among high risk individuals; its consistent intake is highly effective in preventing HIV infection [6]

Summary

Introduction

Human immunodeficiency virus (HIV) infection remains a leading public health problem, due to the rapid mutation of the virus, resistance to existing therapies, lack of a vaccine, and inadequate use of physical prophylaxis, for example, resistance to condom use for cultural or religious reasons [1]. A number of plant and microbial lectins have been researched in recent years, including griffithsin (GRFT), actinohivin (AH), concanavalin-A (ConA), cyanovirin-N (CV-N), microvirin (MVN), and banana lectin (BanLec) Speaking, these lectins contain multiple sugarbinding sites allowing them to form multivalent interactions with gp120. Similar to the above carbohydrate-binding proteins, BanLec inhibits HIV infection at the viral entry step by binding to high-mannose structures present on the heavily glycosylated gp120 in a concentration dependent manner, preventing attachment of the virus to the cell. GRFT is currently the leading lectin candidate for clinical use as an HIV prophylactic, neutralizing HIV with IC50 in the picomolar range [45] This lectin is more potent than broadly neutralizing antibodies (bNAbs), including 2G12 which binds to high-mannose-type glycans. GRFT has an excellent safety profile when tested in a rabbit vaginal irritancy model [46], with minimal toxicity when administered in single or chronic subcutaneous doses in mice and guinea pigs [47]

Lectins Are Active against Viruses Other Than HIV

Findings

Conclusion