Antiviral Activities of Human Host Defense Peptides

Abstract

Peptides with broad-spectrum antimicrobial activity are found widely expressed throughout nature. As they participate in a number of different aspects of innate immunity in mammals, they have been termed Host Defense Peptides (HDPs). Due to their common structural features, including an amphipathic structure and cationic charge, they have been widely shown to interact with and disrupt microbial membranes. Thus, it is not surprising that human HDPs have activity against enveloped viruses as well as bacteria and fungi. However, these peptides also exhibit activity against a wide range of non-enveloped viruses as well, acting at a number of different steps in viral infection. This review focuses on the activity of human host defense peptides, including alpha- and beta-defensins and the sole human cathelicidin, LL-37, against both enveloped and non-enveloped viruses. The broad spectrum of antiviral activity of these peptides, both in vitro and in vivo suggest that they play an important role in the innate antiviral defense against viral infections. Furthermore, the literature suggests that they may be developed into antiviral therapeutic agents.

Type I interferon and interferon‐stimulated gene expression in oral epithelial cells

“…(a) “Ready” OECs are not stimulated by danger‐associated molecular patterns (DAMPs) and, therefore, do not express pro‐inflammatory cytokines. However, despite not expressing the full repertoire of either type I interferon (type I IFN) or antimicrobial peptides (also known as host defense peptides, HDPs), OECs do express some of these proteins constitutively, leading to direct antiviral activity mediated by human beta defensin 1 (HBD1) (Brice & Diamond, ; Zhao, Wang, & Lehrer, ) and certain interferon‐stimulated genes (ISGs) that target early aspects of the viral lifecycle. (b) OECs become “active” when stimulated with DAMPs, leading to transcription of a larger number of pro‐inflammatory cytokines, HDPs, and type I IFN, each with their own antiviral effects…”

“…While these PRRs bind to a wide variety of molecular patterns, each with their own degree of promiscuity for ligands (Seong & Matzinger, ), their activation pathway includes a number of similar transcription factors: nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB), activator protein 1 (AP‐1), and interferon regulatory factors (IRFs) (Brubaker et al, ). These transcription factors translocate to the nucleus upon activation and lead to the expression of genes encoding for pro‐inflammatory cytokines and interferons (Parkin & Cohen, ) as well as antimicrobial peptides, which exhibit antiviral activity (Brice & Diamond, ).…”

Network Medicine Approach for Analysis of Alzheimer’s Disease Gene Expression Data

“…Notably, this hub contains the aforementioned BPI gene, as well has the haptoglobin genes (HP) and the DEFA4 gene. BPI and DEFA4 both code for components of the immune system; the latter is a defensin, which are known for disrupting microbial membranes, while the former is a protein involved in enhancing immune-cell bacterial recognition [33,34]. There may in fact be a connection between these immune genes and the haptoglobin gene, as findings suggest that haptoglobin has a role in the regulation of the immune system; haptoglobin deficient mice have a reduction in the presence of T and B cells, and they exhibit overall inhibited adaptive immune responses [35].…”

A broad-spectrum virus- and host-targeting antiviral peptide against SARS-CoV-2 and other respiratory viruses

“…We have also reported antiviral peptides against influenza virus by delivering defective interfering gene 14 , zika virus by targeting envelope protein 15 , MERS-CoV by blocking viral fusion 16 . Other groups have reported the broad-spectrum antiviral peptide BanLec inhibiting HIV, hepatitis C virus (HCV) and influenza virus 17 , retrocyline 2 inhibiting influenza virus, Sindbis virus, and baculovirus 18 , mastoparan inhibiting enveloped viruses 19 , mucroporin-M1 inhibiting measles, SARS-CoV and H5N1 virus 20 , Ev37 inhibiting dengue virus, HCV, zika virus, and herpes simples virus 21 , and other host defense peptides inhibiting different enveloped and no-enveloped viruses with documented or unknown mechanism [22][23][24] . Since the first anti-HIV peptide enfuvirtide was approved by FDA for the treatment of HIV in 2003 25 , other peptides with antiviral activity have been approved by FDA 26 .…”