Griffithsin: An Antiviral Lectin with Outstanding Therapeutic Potential

Lusvarghi, Sabrina; Bewley, Carole A.

doi:10.3390/v8100296

Cited by 116 publications

(119 citation statements)

References 54 publications

(152 reference statements)

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“…Among non-legume lectins, griffithsin (GRFT), cyanovirin (CV-N) and banana lectin (BanLec) (Swanson et al, 2010) are known to have antiviral effect. Very often, these lectins are incorporated into vaginal and rectal gels, creams and suppositories to prevent HIV transmission (Lusvarghi and Bewley, 2016). Here, lectins bind viruses and block their entry and fusion to target cells by averting infection.…”

Section: Antiviral Activity Of Lectinsmentioning

confidence: 99%

Structure-function and application of plant lectins in disease biology and immunity

Mishra

Behura

Mawatwal

et al. 2019

Food and Chemical Toxicology

131

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A B S T R A C TLectins are proteins with a high degree of stereospecificity to recognize various sugar structures and form reversible linkages upon interaction with glyco-conjugate complexes. These are abundantly found in plants, animals and many other species and are known to agglutinate various blood groups of erythrocytes. Further, due to the unique carbohydrate recognition property, lectins have been extensively used in many biological functions that make use of protein-carbohydrate recognition like detection, isolation and characterization of glycoconjugates, histochemistry of cells and tissues, tumor cell recognition and many more. In this review, we have summarized the immunomodulatory effects of plant lectins and their effects against diseases, including antimicrobial action. We found that many plant lectins mediate its microbicidal activity by triggering host immune responses that result in the release of several cytokines followed by activation of effector mechanism. Moreover, certain lectins also enhance the phagocytic activity of macrophages during microbial infections. Lectins along with heat killed microbes can act as vaccine to provide long term protection from deadly microbes. Hence, lectin based therapy can be used as a better substitute to fight microbial diseases efficiently in future.

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Section: Antiviral Activity Of Lectinsmentioning

confidence: 99%

Structure-function and application of plant lectins in disease biology and immunity

Mishra

Behura

Mawatwal

et al. 2019

Food and Chemical Toxicology

131

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“…CD4 binding induces changes in gp120 resulting in the exposure of envelope domains, which were previously hidden at the moment it binds to the host cells. 33 Interestingly, several lectins with anti-HIV activity show recognition of different carbohydrates. It is difficult for antibodies to reach the initiallyuncovered surface protein domains efficiently, which also means that efficient vaccines are not available yet for HIV.…”

Section: Discussionmentioning

confidence: 99%

“…Such uncovered domains may then bind to the CXCR4 or CCR5 co-receptors on the cell membrane. 31,34 Griffithsin binds to mannose/glucose structures, cyanovirin N predominantly binds to alphaĲ1,2)-mannose structures, Galanthus nivalis agglutinin (GNA) and Hippeastrum hybrid agglutinin exhibit α(1,3)/α(1,6)-mannose-binding activity 33 and Musa acuminata agglutinin (BanLec) binds to high mannose carbohydrate structures. 31 The HIV surface glycoprotein gp120 is one of the most heavily glycosylated proteins known so far, and its molecular weight consists of ∼50% of glycans.…”

Section: Discussionmentioning

confidence: 99%

“…31 The HIV surface glycoprotein gp120 is one of the most heavily glycosylated proteins known so far, and its molecular weight consists of ∼50% of glycans. 33 They block viral entry as the major mechanism of antiviral activity. 32 Indeed, due to their high specificity for binding to carbohydrate chains on cell surfaces, lectins are widely studied in the glycobiology field, and participate in many important physiological processes.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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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 EC 50 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 EC 50 of 5 nM, and DSclerL, ConBr and ConM showed remarkably low EC 50 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 EC 50 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. 390 | Med. Chem. Commun., 2019, 10, 390-398 This journal is

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“…Griffithsin, a protein from red seaweeds, is another drug with the same mechanism of action. Studies to date are encouraging, as they have demonstrated its activity in picomolar concentrations and absence of irritability and inflammation 60,61. It has also been successfully expressed and purified from transgenic plants, which would make it more economical 60,62–64.…”

Section: Historical Development Of Vaginal Microbicidesmentioning

confidence: 98%

Historical development of vaginal microbicides to prevent sexual transmission of HIV in women: from past failures to future hopes

Notario-Pérez¹,

Ruíz-Caro²,

Veiga-Ochoa³

2017

DDDT

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Infection with human immunodeficiency virus (HIV) remains a global public health concern and is particularly serious in low- and middle-income countries. Widespread sexual violence and poverty, among other factors, increase the risk of infection in women, while currently available prevention methods are outside the control of most. This has driven the study of vaginal microbicides to prevent sexual transmission of HIV from men to women in recent decades. The first microbicides evaluated were formulated as gels for daily use and contained different substances such as surfactants, acidifiers and monoclonal antibodies, which failed to demonstrate efficacy in clinical trials. A gel containing the reverse transcriptase inhibitor tenofovir showed protective efficacy in women. However, the lack of adherence by patients led to the search for dosage forms capable of releasing the active principle for longer periods, and hence to the emergence of the vaginal ring loaded with dapivirine, which requires a monthly application and is able to reduce the sexual transmission of HIV. The future of vaginal microbicides will feature the use of alternative dosage forms, nanosystems for drug release and probiotics, which have emerged as potential microbicides but are still in the early stages of development. Protecting women with vaginal microbicide formulations would, therefore, be a valuable tool for avoiding sexual transmission of HIV.

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Griffithsin: An Antiviral Lectin with Outstanding Therapeutic Potential

Cited by 116 publications

References 54 publications

Structure-function and application of plant lectins in disease biology and immunity

Structure-function and application of plant lectins in disease biology and immunity

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

Historical development of vaginal microbicides to prevent sexual transmission of HIV in women: from past failures to future hopes

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