In Ovo Delivered Toll-Like Receptor 7 Ligand, Resiquimod Enhances Host Responses against Infectious Bronchitis Corona Virus (IBV) Infection

Abstract

M.A.); arunavetlk@gmail.com (A.A.); mohamedsarjoon.moham@ucalgary.ca (M.S.A.-C.); mmczub@ucalgary.ca (M.C.)Abstract: Toll-like receptor (TLR) 7 ligand, resiquimod, has been studied as an adjuvant and antiviral agent against several pathogens in chicken. Yet, the effectiveness of resiquimod against infectious bronchitis virus (IBV) infection has not been evaluated. In this study, we investigated the effectiveness of resiquimod delivered pre-hatch (in ovo) against IBV infection post-hatch identifying key mechanisms involved in resiquimod driven immune activation. First, we found an upregulation of interleukin (IL)-1β and interferon (IFN)-γ mRNA levels and considerable expansions of macrophage and cluster of differentiation (CD) 8α+ T cell populations in lungs of chicken as early as day one post-hatch, following pre-hatch delivery of resiquimod. Second, we observed that resiquimod was able to act as an adjuvant when resiquimod was delivered pre-hatch along with an inactivated IBV vaccine. Finally, when the resiquimod pretreated one-day-old chickens were infected with IBV, reduction in viral shedding via oral and fecal routes was observed at 3 days postinfection. Overall, this study shows that the pre-hatch delivered resiquimod increases cell-mediated immune responses in lungs with an advantage of reduction in IBV shedding.

Toll-like Receptor Ligands Enhance Vaccine Efficacy against a Virulent Newcastle Disease Virus Challenge in Chickens

“…Imiquimod has also been tested as one of the many adjuvant components for enhancing inactivated vaccines against avian influenza in chickens and ducks, but its individual role in enhancing vaccine efficacy is unclear [28,29]. Resiquimod (R848), a structurally related immunomodulator, has been more frequently tested in chickens (compared with imiquimod) [30][31][32][33][34] and tested as an adjuvant for an inactivated NDV vaccine, where an enhanced humoral and cellular immune response was observed [35,36].…”

Design and synthesis of heterocyclic azole based bioactive compounds: Molecular structures, quantum simulation, and mechanistic studies through docking as multi-target inhibitors of SARS-CoV-2 and cytotoxicity

“…CQ and HCQ are also suggested to block the virus entry through glycosylation of host ACE-2 receptor. Remdesivir showed inhibition activity against a variety of non-structural proteins such as RdRp [ 4 , 5 ].…”

“…To date, due to its high toxicity and the virus resistance to the drug, no effective dedicated treatments are approved for treating such CoVs. The development of new therapeutic anticorona agents made so far has also been limited [ 4 , 5 ]. Heterocyclic compounds such as triazole, thiazole, pyrrole, pyridine, quinolone, etc., and their derivatives are characterized as important classes of organic compounds that exhibit various biological and medicinal properties such as antitumor [ 6 , 7 ], EGFR inhibitory [8] , antioxidant [ 9 , 10 ], antianalgesic, antiinflammatory [11] , antibacterial [12] , antifungal [13] , antimicrobial [14] , etc .…”