Lectins are carbohydrate-binding proteins that are highly specific for sugar groups that are part of other molecules, so cause agglutination of particular cells or precipitation of glycoconjugates and polysaccharides. Lectins have a role in recognition at the cellular and molecular level and play numerous roles in biological recognition phenomena involving cells, carbohydrates, and proteins. Lectins also mediate attachment and binding of bacteria, viruses, and fungi to their intended targets.
Influenza hemagglutinin (HA) or haemagglutinin[p] is a homotrimeric glycoprotein found on the surface of influenza viruses and is integral to its infectivity.
DC-SIGN also known as CD209 is a protein which in humans is encoded by the CD209 gene.
Envelope glycoprotein GP120 is a glycoprotein exposed on the surface of the HIV envelope. It was discovered by Professors Tun-Hou Lee and Myron "Max" Essex of the Harvard School of Public Health in 1984. The 120 in its name comes from its molecular weight of 120 kDa. Gp120 is essential for virus entry into cells as it plays a vital role in attachment to specific cell surface receptors. These receptors are DC-SIGN, Heparan Sulfate Proteoglycan and a specific interaction with the CD4 receptor, particularly on helper T-cells. Binding to CD4 induces the start of a cascade of conformational changes in gp120 and gp41 that lead to the fusion of the viral membrane with the host cell membrane. Binding to CD4 is mainly electrostatic although there are van der Waals interactions and hydrogen bonds.
Viral infectivity factor, or Vif, is an accessory protein found in HIV and other lentiviruses. Its role is to disrupt the antiviral activity of the human enzyme APOBEC by targeting it for ubiquitination and cellular degradation. APOBEC is a cytidine deaminase enzyme that mutates viral nucleic acids.
Viral entry is the earliest stage of infection in the viral life cycle, as the virus comes into contact with the host cell and introduces viral material into the cell. The major steps involved in viral entry are shown below. Despite the variation among viruses, there are several shared generalities concerning viral entry.
Cyanovirin-N (CV-N) is a protein produced by the cyanobacterium Nostoc ellipsosporum that displays virucidal activity against several viruses, including human immunodeficiency virus (HIV). A cyanobacterial protein called cyanovirin-N (CV-N) has strong anti-human immunodeficiency virus (HIV) neutralizing properties. The virucidal activity of CV-N is mediated through specific high-affinity interactions with the viral surface envelope glycoproteins gp120 and gp41, as well as to high-mannose oligosaccharides found on the HIV envelope. In addition, CV-N is active against rhinoviruses, human parainfluenza virus, respiratory syncytial virus, and enteric viruses. The virucidal activity of CV-N against influenza virus is directed towards viral haemagglutinin.
Entry inhibitors, also known as fusion inhibitors, are a class of antiviral drugs that prevent a virus from entering a cell, for example, by blocking a receptor. Entry inhibitors are used to treat conditions such as HIV and hepatitis D.
Galectins are a class of proteins that bind specifically to β-galactoside sugars, such as N-acetyllactosamine, which can be bound to proteins by either N-linked or O-linked glycosylation. They are also termed S-type lectins due to their dependency on disulphide bonds for stability and carbohydrate binding. There have been about 15 galectins discovered in mammals, encoded by the LGALS genes, which are numbered in a consecutive manner. Only galectin-1, -2, -3, -4, -7, -7B, -8, -9, -9B, 9C, -10, -12, -13, -14, and -16 have been identified in humans. Galectin-5 and -6 are found in rodents, whereas galectin-11 and -15 are uniquely found in sheep and goats. Members of the galectin family have also been discovered in other mammals, birds, amphibians, fish, nematodes, sponges, and some fungi. Unlike the majority of lectins they are not membrane bound, but soluble proteins with both intra- and extracellular functions. They have distinct but overlapping distributions but found primarily in the cytosol, nucleus, extracellular matrix or in circulation. Although many galectins must be secreted, they do not have a typical signal peptide required for classical secretion. The mechanism and reason for this non-classical secretion pathway is unknown.
Langerin (CD207) is a type II transmembrane protein which is encoded by the CD207 gene in humans. It was discovered by scientists Sem Saeland and Jenny Valladeau as a main part of Birbeck granules. Langerin is C-type lectin receptor on Langerhans cells (LCs) and in mice also on dermal interstitial CD103+ dendritic cells (DC) and on resident CD8+ DC in lymph nodes.
C-type lectin domain family 4 member M is a protein that in humans is encoded by the CLEC4M gene. CLEC4M has also been designated as CD299.
Neutral alpha-glucosidase C is an enzyme that in humans is encoded by the GANC gene.
Viral neuraminidase is a type of neuraminidase found on the surface of influenza viruses that enables the virus to be released from the host cell. Neuraminidases are enzymes that cleave sialic acid groups from glycoproteins. Viral neuraminidase was discovered by Alfred Gottschalk at the Walter and Eliza Hall Institute in 1957. Neuraminidase inhibitors are antiviral agents that inhibit influenza viral neuraminidase activity and are of major importance in the control of influenza.
CCR5 receptor antagonists are a class of small molecules that antagonize the CCR5 receptor. The C-C motif chemokine receptor CCR5 is involved in the process by which HIV, the virus that causes AIDS, enters cells. Hence antagonists of this receptor are entry inhibitors and have potential therapeutic applications in the treatment of HIV infections.
BanLec is a lectin from the jacalin-related lectin family isolated from the fruit of the bananas Musa acuminata and Musa balbisiana. BanLec is one of the predominant proteins in the pulp of ripe bananas and has binding specificity for mannose and mannose-containing oligosaccharides. A 2010 study reported that BanLec was a potent inhibitor of HIV replication.
In molecular biology, the CVNH domain is a conserved protein domain. It is found in the sugar-binding antiviral protein cyanovirin-N (CVN) as well as proteins from filamentous ascomycetes and in the fern Ceratopteris richardii.
In molecular biology, the jacalin-like lectin domain is a mannose-binding lectin domain with a beta-prism fold consisting of three 4-stranded beta-sheets, with an internal pseudo 3-fold symmetry. Some lectins in this group stimulate distinct T- and B-cell functions, such as Jacalin, which binds to the T-antigen and acts as an agglutinin. This domain is found in 1 to 6 copies in lectins. The domain is also found in the salt-stress induced protein from rice and an animal prostatic spermine-binding protein.
Scytonema varium is a cultured cyanobacterium of the genus Scytonema. It is one of many anti viral protein producing algae. In a similar manner to Cyanovirin-N from Nostoc Ellipsosporum and griffithsin from the red algae Griffithsia, Scytonema varium secretes the broad-spectrum antiviral protein scytovirin which can inactivate both the HIV virus, and Ebola virus, offering hope of treatment for many diseases with viral etiology (cause). It is currently being investigated as a topical microbicide for HIV prophylaxis.
Scytovirin is a 95-amino acid antiviral protein isolated from the cyanobacteria Scytonema varium. It has been cultured in E. coli and its structure investigated in detail. Scytovirin is thought to be produced by the bacteria to protect itself from viruses that might otherwise attack it, but as it has broad-spectrum antiviral activity against a range of enveloped viruses, scytovirin has also been found to be useful against a range of major human pathogens, most notably HIV / AIDS but also including SARS coronavirus and filoviruses such as Ebola virus and Marburg virus. While some lectins such as cyanovirin and Urtica dioica agglutinin are thought likely to be too allergenic to be used internally in humans, studies so far on scytovirin and griffithsin have not shown a similar level of immunogenicity. Scytovirin and griffithsin are currently being investigated as potential microbicides for topical use.
In the management of HIV/AIDS, HIV capsid inhibitors are antiretroviral medicines that target the capsid shell of the virus. This is in contrast to most current antiretroviral drugs used to treat HIV, which do not directly target the viral capsid. These have also been termed "Capsid-targeting Antivirals", "Capsid Effectors", and "Capsid Assembly Modulators (CAMs)". Because of this, drugs that specifically inhibit the HIV capsid are being developed in order to reduce the replication of HIV, and treat infections that have become resistant to current antiretroviral therapies.
