Towards the Application of Human Defensins as Antivirals

Abstract

Defensins are antimicrobial peptides that participate in the innate immunity of hosts. Humans constitutively and/or inducibly express α- and β-defensins, which are known for their antiviral and antibacterial activities. This review describes the application of human defensins. We discuss the extant experimental results, limited though they are, to consider the potential applicability of human defensins as antiviral agents. Given their antiviral effects, we propose that basic research be conducted on human defensins that focuses on RNA viruses, such as human immunodeficiency virus (HIV), influenza A virus (IAV), respiratory syncytial virus (RSV), and dengue virus (DENV), which are considered serious human pathogens but have posed huge challenges for vaccine development for different reasons. Concerning the prophylactic and therapeutic applications of defensins, we then discuss the applicability of human defensins as antivirals that has been demonstrated in reports using animal models. Finally, we discuss the potential adjuvant-like activity of human defensins and propose an exploration of the ‘defensin vaccine’ concept to prime the body with a controlled supply of human defensins. In sum, we suggest a conceptual framework to achieve the practical application of human defensins to combat viral infections.

The human α-defensin-derived peptide HD5(1-9) inhibits cellular attachment and entry of human cytomegalovirus

“…Arginine (Arg) residues were suggested to participate in HD5-membrane interactions, and hence HD5-mediated antimicrobial effects (30). Furthermore, Cysteine (Cys) at positions three and five are involved in forming disulfide bridges in the context of the full length protein and contribute to the biological activity of defensins (7, 16, 31). Therefore, we ordered three HD5(1-9) modified peptides: HD5(1-9)[R>A], where two Arg residues were mutated to alanine (Ala); HD5(1-9)[C>S] where both Cys were mutated to serine (Ser) and HD5(1-9)[C3S; C5R] where Cys3 was mutated to Ser and Cys5 to Arg.…”

“…Defensins have been described as antiviral effector molecules of various viruses with different potential modes of action (16, 34). Nevertheless, this is the first comprehensive report demonstrating antiviral activity of a defensin against HCMV and in particular of the α-defensin HD5-derived peptide HD5(1-9).…”

“…Although less studied, defensins also have antiviral activity (15, 16). For instance, α-defensins inhibit herpes simplex virus-2 (HSV-2) by interacting directly with viral particles or cellular heparan sulfates (17, 18).…”

Subversion of host immune responses by otopathogens during otitis media

“…α‐Defensins are expressed in granulocytes and intestinal Paneth cells . When first discovered, α‐defensins were named after the former function, that is, human neutrophil peptide (HNP).…”

New methods of prevention and treatment of acute respiratory viral infections in children. Local protection factors of the respiratory mucosa

“…Дефензины -это пептиды с широким спектром антимикробной активности (противовирусной, антибактериальной, противогрибковой, антипротозойной) [10,11]. Будучи самыми распространенными антимикробными пептидами человека, дефензины играют важную роль в обеспечении врожденного иммунитета [12].…”