Ramping Up Antimicrobial Peptides Against Severe Acute Respiratory Syndrome Coronavirus-2.

Santosh K Ghosh,Aaron Weinberg

doi:10.3389/fmolb.2021.620806

Abstract

Human-derived antimicrobial peptides (AMPs), such as defensins and cathelicidin LL-37, are members of the innate immune system and play a crucial role in early pulmonary defense against viruses. These AMPs achieve viral inhibition through a variety of mechanisms including, but not limited to, direct binding to virions, binding to and modulating host cell-surface receptors, blocking viral replication, and aggregation of viral particles and indirectly by functioning as chemokines to enhance or curb adaptive immune responses. Given the fact that we are in a pandemic of unprecedented severity and the urgent need for therapeutic options to combat severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), naturally expressed AMPs and their derivatives have the potential to combat coronavirus disease 2019 (COVID-19) and impede viral infectivity in various ways. Provided the fact that development of effective treatments is an urgent public health priority, AMPs and their derivatives are being explored as potential prophylactic and therapeutic candidates. Additionally, cell-based platforms such as human mesenchymal stem cell (hMSC) therapy are showing success in saving the lives of severely ill patients infected with SARS-CoV-2. This could be partially due to AMPs released from hMSCs that also act as immunological rheostats to modulate the host inflammatory response. This review highlights the utilization of AMPs in strategies that could be implemented as novel therapeutics, either alone or in combination with other platforms, to treat CoV-2–infected individuals.

Highlights

The ongoing coronavirus disease 2019 (COVID-19) pandemic, the result of infection by SARS-CoV2, continues to spread worldwide and has already claimed the lives of over three million people (John Hopkins University, 2020)
HMSC-related antimicrobial peptides (AMPs), which could include additional yet-to-be–discovered peptides, could be interacting in synergy with other beneficial agents secreted by human mesenchymal stem cell (hMSC), such as exosomal agents that limit immune thrombosis, increase fibrinolytic activity, re-stabilize endothelial integrity, reduce lymphocyte trafficking, and promote recruitment of M2 macrophages and regulatory T cells (Gomzikova et al, 2019; Jamshidi et al, 2021; Moradinasab et al, 2021; Su et al, 2021)
The saying that “desperate diseases call for desperate treatments” cannot be more appropriate during these trying times when a worldwide pandemic is wreaking havoc on mankind

Summary

INTRODUCTION

The ongoing coronavirus disease 2019 (COVID-19) pandemic, the result of infection by SARS-CoV2, continues to spread worldwide and has already claimed the lives of over three million people (John Hopkins University, 2020). Ramping Up AMPs Against SARS-CoV-2 direct activity involving a variety of mechanisms, including membrane permeation, disruption of electrochemical gradients, and inhibition of metabolic processes (Brogden, 2005; Prasad et al, 2019) These peptides interact with multiple receptors on host cells, such as toll-like receptors (TLRs) and chemokine receptors, as well as inflammasomes and members of the host’s complement system, thereby providing a bridge between innate and adaptive immunity (Hancock et al, 2016; Prasad et al, 2019; Mookherjee et al, 2020).

RSV HAdV HRV

CONCLUSION AND PERSPECTIVES