Potent antiviral activity of carbohydrate-specific algal and leguminous lectins from the Brazilian biodiversity.

Ana C S Gondim,Sam Noppen,Jan Balzarini,Leen Mathys,Celso S Nagano,Peter J Sadler,Cintia Renata Costa Rocha,Alexandre Holanda Sampaio,Benildo S Cavada,Kyria S Nascimento,Sandra Liekens,Suzete Roberta Da Silva

doi:10.1039/c8md00508g

Abstract

Brazil has one of the largest biodiversities in the world. The search for new natural products extracted from the Brazilian flora may lead to the discovery of novel drugs with potential to treat infectious and other diseases. Here, we have investigated 9 lectins extracted and purified from the Northeastern Brazilian flora, from both leguminous species: Canavalia brasiliensis (ConBr), C. maritima (ConM), Dioclea lasiocarpa (DLasiL) and D. sclerocarpa (DSclerL), and algae Amansia multifida (AML), Bryothamniom seaforthii (BSL), Hypnea musciformis (HML), Meristiella echinocarpa (MEL) and Solieria filiformis (SfL). They were exposed to a panel of 18 different viruses, including HIV and influenza viruses. Several lectins showed highly potent antiviral activity, often within the low nanomolar range. DSclerL and DLasiL exhibited EC50 values (effective concentration of lectin required to inhibit virus-induced cytopathicity by 50%) of 9 nM to 46 nM for HIV-1 and respiratory syncytial virus (RSV), respectively, DLasiL also inhibited feline corona virus at an EC50 of 5 nM, and DSclerL, ConBr and ConM showed remarkably low EC50 values ranging from 0.4 to 6 nM against influenza A virus strain H3N2 and influenza B virus. For HIV, evidence pointed to the blockage of entry of the virus into its target cells as the underlying mechanism of antiviral action of these lectins. Overall, the most promising lectins based on their EC50 values were DLasiL, DSclerL, ConBr, ConM, SfL and HML. These novel findings indicate that lectins from the Brazilian flora may provide novel antiviral compounds with therapeutic potential.

Highlights

Biological activity has been studied intensely.[1,2,3,4,5] In this context, Brazilian biodiversity can potentially provide a wealth of novel unknown lectins, which can be mined for novel bioactivity
The purified algal and leguminous lectins were initially investigated for their inhibitory activity against two different strains of human immunodeficiency virus (HIV), HIV-1 (NL4.3) and HIV-2 (ROD)
HIV-1 and HIV-2 infection was performed in human CD4+ T-lymphocyte (CEM) cell cultures

Summary

Introduction

Biological activity has been studied intensely.[1,2,3,4,5] In this context, Brazilian biodiversity can potentially provide a wealth of novel unknown lectins, which can be mined for novel bioactivity. Many lectins agglutinate red blood cells derived from several animal species such as mice, rats, rabbits, but not of human origin.[11,14] Microvirin, an alphaIJ1,2)-mannose-specific lectin from Microcystis aeruginosa has been shown to have comparable anti-HIV activity as cyanovirin, but a much higher safety profile It proved 50-fold less cytotoxic than cyanovirin, and it did not increase the level of activation markers in CD4+ T lymphocytes.[15] the highly potent antiviral red algal lectin griffithsin was reported to have an outstanding safety and efficacy profile as a potential microbicidal drug candidate.[16] It induces only minimal changes in secretion of inflammatory cytokines and chemokines by epithelial cells and human PBMCs, does not markedly upregulate T cell activation markers and gene expression, and has no measurable effect on cell viability. Castillo-Acosta et al.[27] recently demonstrated that Pradimicin, a mannosespecific agent purified from Actinomyces madura, can cure mice suffering from acute sleeping sickness caused by trypanosomes

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