Regulators of innate immunity as novel targets for panviral therapeutics

Abstract

Interferons (IFNs) have long been used as an immunomodulatory therapy for a large array of acute and chronic viral infections. However, IFN therapies have been plagued by severe side effects. The discovery of pathogen recognition receptors (PRR) rejuvenated the interest for immunomodulatory therapies. The successes obtained with Toll-like receptor (TLR) agonists in activating immune cells and as adjuvant for prophylactic vaccines against different viruses paved the way to targeted immunomodulatory therapy. Better characterization of pathogen-induced immune disorders and newly discovered regulators of innate immunity have now the potential to specifically withdraw prevailing subversion mechanisms and to transform antiviral treatments by introducing panviral therapeutics with less adverse effects than IFN therapies.

Inhibition of Pyrimidine Biosynthesis Pathway Suppresses Viral Growth through Innate Immunity

“…They also tend to escape drugs that target viral proteins through mutations, thus calling for innovative therapeutic approaches. Among possible strategies, chemical modulators of host pathways [3], [4], [5], [6], and in particular stimulators of innate immune response that boost cellular defenses to eliminate viral pathogens are of growing interest [7], [8], [9], [10]. In principle, such molecules would be efficient against a large panel of viral pathogens since the host immune response relies on a multiplicity of antiviral effectors that block viruses at several steps of their replication, and cover the variety of replication strategies they use.…”

Broad-spectrum inhibition of common respiratory RNA viruses by a pyrimidine synthesis inhibitor with involvement of the host antiviral response

“…Nonetheless, modulation of host pathways for enhancement of the innate immune response through chemicals could be a viable strategy for the development of antiviral therapy, and has been of growing interest recently [25,26]. It can be expected that such immunomodulators are effective against a range of different viral pathogens through the many facets of the host immune response.…”

TLR4 and TLR9 Polymorphisms Effect on Inflammatory Response in End-Stage Renal Disease Patients

“…The TLRs specificity in recognizing most classes of pathogens and their role in the pathogenesis of multiple diseases represents the strongest evidence that TLRs are valuable therapeutic targets. TLR targeted drugs have been approved and small-molecule compounds are being investigated in the treatment of viral infections (29). However, therapeutic modulation by TLRs could cause unexpected unsafe responses that could be avoided with an accurate knowledge about each TLR in the pathophysiology of several diseases (12).…”

“…TLR agonists have been an extensively explored area in the development ofvaccine adjuvants for prophylactic and therapeutic applications, by linking innate and adaptive immune systems (29). The negative regulation of TLR-induced responses is important for suppressing inflammation and deleterious immune responses (11).…”