Novel Drugs Targeting Toll-Like Receptors for Antiviral Therapy

Abstract

Toll-like receptors (TLRs) are sentinel receptors of the host innate immune system that recognize conserved ‘pathogen-associated molecular patterns’ of invading microbes, including viruses. The activation of TLRs establishes antiviral innate immune responses and coordinates the development of long-lasting adaptive immunity in order to control viral pathogenesis. However, microbe-induced damage to host tissues may release ‘danger-associated molecular patterns’ that also activate TLRs, leading to an overexuberant inflammatory response and, ultimately, to tissue damage. Thus, TLRs have proven to be promising targets as therapeutics for the treatment of viral infections that result in inflammatory damage or as adjuvants in order to enhance the efficacy of vaccines. Here, we explore recent advances in TLR biology with a focus on novel drugs that target TLRs (agonists and antagonists) for antiviral therapy.

Cytosolic Sensors of Viral RNA Are Involved in the Production of Interleukin-6 via Toll-Like Receptor 3 Signaling in Human Glomerular Endothelial Cells

“…On the other hand, it is notably that TLR3 signaling has both protective and deleterious effects in the pathogenesis of virus and “pseudoviral” infections [24]. Also, TLR3 agonist poly IC used in this experiment sometimes promote apoptosis and increase cellular permeability in some cell types [24]. Thus, we should be careful to interpret our preliminary findings.…”

Toll-like Receptors in the Vascular System: Sensing the Dangers Within

“…Specific TLR agonists with low toxicity and high potency are preferred over other adjuvants for the development of prophylactic vaccines (Wille-Reece et al, 2005;Halperin et al, 2006;Gupta et al, 2014;Bortolatto et al, 2015). Furthermore, preclinical data support the use of TLR3, TLR4, TLR7, and TLR7/8 agonists to enhance vaccines against cancer and viral diseases (Patel et al, 2014;Zhao et al, 2014;Shirota et al, 2015). TLR agonists that induce a shift in T H 2/T H 1 ratio have also been developed for treatment of allergic diseases and asthma (Asai et al, 2008;Horak, 2011;Aryan et al, 2014).…”

Peripheral blood toll-like receptor 4 correlates response to candida immunotherapy of warts

“…They recognize microbial antigens, including viruses. TLRs activation causes antiviral innate immune responses with subsequent development of adaptive immunity (Patel et al, 2014). After the characterization of the first mammalian TLR, TLR4, several proteins that are structurally related to TLR4 were identified and named TLRs (Rock, Hardiman, Timans, Kastelein, & Bazan, 1998).…”