TLR4 as a therapeutic target for respiratory and neurological complications of SARS-CoV-2.

INTRODUCTION: The COVID-19 pandemic remains a global challenge. While there are mRNA agents on the horizon as a potential prevention, a definitive drug therapy is an unmet medical need. The hyperinflammatory response, known as the 'cytokine storm', is chiefly responsible for complications and deaths. The binding of spike-glycoprotein of SARS-CoV-2 to TLR4 receptors has been documented in several studies and has been found to play a role in hyperinflammation, hence there is an interest in TLR4 as a potential drug target.Areas Covered:This review discusses the neurological and respiratory complications of SARS-CoV-2 infection and progresses to examine the role of the 'cytokine storm' and the involvement of TLR4 receptors in these complications. The possibility of using TLR4 modulators to curb the complications are considered and finally, a short perspective on future potential drug treatments is offered. Various databases were searched including Pub-Med, Google Scholar, and Medline. The search mainly included research articles, meta-analysis, retrospective studies, reports, and systematic reviews.Expert Opinion:TLR4 modulators are being investigated in clinical trials for COVID-19. Challenges in terms of structural diversity of the agents, their natural origin and efficacy demand extensive research.