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M. Irfan et al.
its zinc metalloprotease activity. LF toxicity cascade can be disrupted by blocking
the interaction between LF and MEK1. AssDNA aptamerML12 was selected against
LF with strong inhibitory activity. ML12 prevented the protease activity by blocking
the active site of LF, hence served as a promising drug candidate for neutralization
of LF toxicity [65].
Botulism is an important syndrome induced by botulinum neurotoxins (BoNT)
secreted by Clostridium botulinum. The main causes of human illness are types A,
B, and E BoNTs and type A is the strongest one and even considered as bio-weapon
among other serotypes. BoNT is secreted as an inactive protein of 150 kDa, which is
cleaved into heavy chains (HCs) of 100 kDa and light chains of 50 kDa linked by a
single disulfide bond. The HCs protein is non-toxic subunit with zinc-endopeptidase
activity and involved in endocytosis of toxin molecule by target nerve cells. The LCs
protein blocks the neurotransmission at peripheral cholinergic synapses by arresting
the protein-mediated release of acetylcholine. Three aptamers were reported against
BoNT as inhibitors of LCs and endopeptidase activity [66].
Mycobacterium tuberculosis (MTB) is another important human pathogen with
smart developed mechanisms of drug resistance and survives in the lungs by
confusing our immune system [67]. MTB persistence is due to the intracellular
metabolism of inorganic polyphosphate (polyP) which is regulated by polyphosphate kinase (PPK) gene. The inhibition of PPK activity by aptamer G9 resulted
in the obstruction of polyP-dependent processes. A concentration of 1 μM of G9
aptamer as therapeutic agent could completely inhibit PPK2 protein of bacteria [68].
7.2.2.2 Aptamer Against Viral Diseases
The treatment of viral infections is an intractable problem for human health, which
highlighted the application of aptamers in antiviral therapy in recent years. The entry
of virus into host cell can be blocked by occupying the viral receptor-binding domain
(RBD) or cell surface receptors (Fig. 7.4). For example, nucleolin is a cell surface
protein used for viral attachment and leads to the cell entry [69, 70]. Nucleolin
takes part in the development of infectious particles after binding with dengue virus
capsid protein. This interaction was reported to be blocked by AS1411, an RNA
aptamer, which interacted with nucleolin [71]. With reference to the approach of
blocking the viral surface proteins taking part in receptor binding, an RNA aptamer
(HA12-16) impeded influenza virus infection in susceptible cells by occupying the
RBD of glycoprotein HA which is responsible for attachment of virus to sialic acid
receptor on the host cell [72–74]. Also, C7-35 M, a modified DNA aptamer which
was designed to target the AIV H9-type HA protein’s globular region suppressed the
viral attachment to host cells [75]. The gD envelope protein of herpes simplex virus
is a key player in the penetration process as it recognizes two protein receptors on
target cells, nectin-1, and herpes virus entry mediator [76]. By considering this theory,
two RNA aptamers against herpes simplex virus-1 were selected, which blocked the
interaction of herpes virus entry mediator with gD protein. It was also observed that
M. Irfan et al.
its zinc metalloprotease activity. LF toxicity cascade can be disrupted by blocking
the interaction between LF and MEK1. AssDNA aptamerML12 was selected against
LF with strong inhibitory activity. ML12 prevented the protease activity by blocking
the active site of LF, hence served as a promising drug candidate for neutralization
of LF toxicity [65].
Botulism is an important syndrome induced by botulinum neurotoxins (BoNT)
secreted by Clostridium botulinum. The main causes of human illness are types A,
B, and E BoNTs and type A is the strongest one and even considered as bio-weapon
among other serotypes. BoNT is secreted as an inactive protein of 150 kDa, which is
cleaved into heavy chains (HCs) of 100 kDa and light chains of 50 kDa linked by a
single disulfide bond. The HCs protein is non-toxic subunit with zinc-endopeptidase
activity and involved in endocytosis of toxin molecule by target nerve cells. The LCs
protein blocks the neurotransmission at peripheral cholinergic synapses by arresting
the protein-mediated release of acetylcholine. Three aptamers were reported against
BoNT as inhibitors of LCs and endopeptidase activity [66].
Mycobacterium tuberculosis (MTB) is another important human pathogen with
smart developed mechanisms of drug resistance and survives in the lungs by
confusing our immune system [67]. MTB persistence is due to the intracellular
metabolism of inorganic polyphosphate (polyP) which is regulated by polyphosphate kinase (PPK) gene. The inhibition of PPK activity by aptamer G9 resulted
in the obstruction of polyP-dependent processes. A concentration of 1 μM of G9
aptamer as therapeutic agent could completely inhibit PPK2 protein of bacteria [68].
7.2.2.2 Aptamer Against Viral Diseases
The treatment of viral infections is an intractable problem for human health, which
highlighted the application of aptamers in antiviral therapy in recent years. The entry
of virus into host cell can be blocked by occupying the viral receptor-binding domain
(RBD) or cell surface receptors (Fig. 7.4). For example, nucleolin is a cell surface
protein used for viral attachment and leads to the cell entry [69, 70]. Nucleolin
takes part in the development of infectious particles after binding with dengue virus
capsid protein. This interaction was reported to be blocked by AS1411, an RNA
aptamer, which interacted with nucleolin [71]. With reference to the approach of
blocking the viral surface proteins taking part in receptor binding, an RNA aptamer
(HA12-16) impeded influenza virus infection in susceptible cells by occupying the
RBD of glycoprotein HA which is responsible for attachment of virus to sialic acid
receptor on the host cell [72–74]. Also, C7-35 M, a modified DNA aptamer which
was designed to target the AIV H9-type HA protein’s globular region suppressed the
viral attachment to host cells [75]. The gD envelope protein of herpes simplex virus
is a key player in the penetration process as it recognizes two protein receptors on
target cells, nectin-1, and herpes virus entry mediator [76]. By considering this theory,
two RNA aptamers against herpes simplex virus-1 were selected, which blocked the
interaction of herpes virus entry mediator with gD protein. It was also observed that