key: cord-1054965-7xs11vtx
authors: Chakraborty, Chiranjib; Sharma, Ashish Ranjan; Bhattacharya, Manojit; Sharma, Garima; Lee, Sang‐Soo; Agoramoorthy, Govindasamy
title: Consider TLR5 for new therapeutic development against COVID‐19
date: 2020-05-22
journal: J Med Virol
DOI: 10.1002/jmv.25997
sha: 709c0ee3cfa370ae100fb6909a2a06aa684770ac
doc_id: 1054965
cord_uid: 7xs11vtx

TLR5, a member of Toll-like receptors (TLRs), has a significant role to recognize the flagellin or same kind of molecule. After reorganization, it can modulate innate immune responses. In this article, we urge for the development of new therapeutic molecule by targeting TLR5 modulation against SARS-CoV-2. This article is protected by copyright. All rights reserved.

which is very timely.

As of 6 May 2020, 247 503 people died so far due to COVID-19, so an efficient treatment procedure is urgently needed. Therefore, scientists are developing new therapeutics molecules focusing on antiviral drugs and novel vaccines. The toll-like receptor 5 (TLR5) evoke innate immune responses 2 and also act as an immune sensor.

The TLR signaling pathway plays a vital role in various host immune defense mechanisms. For immunotherapeutic development, this pathway modulation identified as a drug target for many antibacterial or antiviral drug development. 3 However, TLR5 is expressed in different immune cells such as dendritic cells, monocytes, and so forth. It is also expressed on the respiratory epithelium cells and pneumonocytes in humans. 4 Therefore, TLR5 can stimulate early signaling that provides protective innate immunity against respiratory infection. Respiratory infection is one of the common symptoms associated with COVID-19 and therefore, TLR5 can incite early signaling to generate protective innate immunity against respiratory infections.

Flagellin, a structural protein of bacteria helps in the process of the adhesion and invasion of pathogenic bacteria into host cells and act as a virulence factor; it is reported as a highly conserved protein. 5 Actually, TLR5 can sense, detect, and binds to natural bacterial flagellin as a ligand. Therefore, an early TLR5 activation through flagellin or similar molecule like flagelin may enhance immunogenicity for immunotherapeutic development. This process is found to be effective in several vaccine models. 6 The new therapeutic strategy by targeting TLR5 modulation may serve as a better choice for vaccine or adjuvant development of SARS-CoV-2. Using the bioinformatics methods, scientists have shown that an epitope-based peptide vaccine component against SARS-CoV-2 docked successfully with TLR5 strengthening the binding affinity. 1 Another study developed SARS-CoV-2 subunit recombinant vaccines using coronaviruses-S1 subunit that was TLR5

agonists. 10 These studies support our conceptualized idea that TLR5 activation can be an effective therapeutic molecule to eradicate SARS-CoV-2.

We recommend the use of active immunomodulation through 12 The elevated neutrophil level is due to the neutrophil extracellular traps (NETs) and increased reactive oxygen species (ROS). Studies suggest that the deoxyribonuclease I-mediated restoration NETs and ROS along with the TLR5 modulation. 13 

Development of epitopebased peptide vaccine against novel coronavirus 2019 (SARS-COV-2): immunoinformatics approach

TLR5: beyond the recognition of flagellin

TLR agonists as modulators of the innate immune response and their potential as agents against infectious disease

Frontline science: nasal epithelial GM-CSF contributes to TLR5-mediated modulation of airway dendritic cells and subsequent IgA response

A conserved TLR5 binding and activation hot spot on flagellin

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Toll-like receptor 5 agonist flagellin reduces influenza A virus replication independently of type I interferon and interleukin 22 and improves antiviral efficacy of oseltamivir

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Microneedle array delivered recombinant coronavirus vaccines: Immunogenicity and rapid translational development

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Harnessing innate immunity to eliminate SARS-CoV-2 and ameliorate COVID-19 disease