Toll-like receptor (TLRs) agonists and antagonists for COVID-19 treatments

Abstract

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) rapidly infects humans and animals which make coronavirus disease 2019 (COVID-19) a grievous epidemic worldwide which broke out in 2020. According to data analysis of the other coronavirus family, for instance severe acute respiratory syndrome SARS coronavirus (SARS-CoV), can provide experience for the mutation of SARS-CoV-2 and the prevention and treatment of COVID-19. Toll-like receptors (TLRs) as a pattern recognition receptor (PRRs), have an indispensable function in identifying the invader even activate the innate immune system. It is possible for organism to activate different TLR pathways which leads to secretion of proinflammatory cytokines such as Interleukin 1 (IL-1), Interleukin 6 (IL-6), Tumor necrosis factor α (TNFα) and type Ⅰ interferon. As a component of non-specific immunity, TLRs pathway may participate in the SARS-CoV-2 pathogenic processes, due to previous works have proved that TLRs are involved in the invasion and infection of SARS-CoV and MERS to varying degrees. Different TLR, such as TLR2, TLR4, TLR7, TLR8 and TLR9 probably have a double-sided in COVID-19 infection. Therefore, it is of great significance for a correctly acknowledging how TLR take part in the SARS-CoV-2 pathogenic processes, which will be the development of treatment and prevention strategies.

Toll‐like receptors in health and disease

“…Their therapeutic use is expected as well, considering the important function played by the molecules in the TLR pathway in the innate immune system; however, this is probably because immune cells and/or cancer cells activate distinct TLRs and downstream signaling cascades; alternatively, because of the temporal sequence of TLR activation in cancer cells or immune cells, studies on the role of TLR antagonists and agonists in inflammation and even cancer have been controversial (Table 2 ). 41 , 321 , 322 , 323 …”

Interplay of host and viral factors in inflammatory pathway mediated cytokine storm during RNA virus infection

“…IL-6 antagonists such as Tocluzimab and IL-6 inhibitors such as Chloroquine were also shown to be efficient in the treatment of CS associated with virus diseases (multicenter collaboration group of Department of, Technology of Guangdong, and Health Commission of Guangdong Province for chloroquine in the treatment of novel coronavirus 2020 ; Tanaka et al, 2016 ). TLR agonists and antagonists were also shown to have therapeutic potential against CS associated with RNA virus infection ( Liu et al, 2022 ).…”

Cellular Sensors and Viral Countermeasures: A Molecular Arms Race between Host and SARS-CoV-2

“…Therefore, targeting PRRs and related pathways could attenuate the hyperactivation of immune response and reduce cytokine storm. Indeed, several studies have demonstrated that PRR antagonists have beneficial roles and might be used as potential therapeutic drugs for COVID-19, though the exact dosage and duration should be carefully evaluated and tested before clinical use [ 141 , 142 , 143 ]. Timing is crucial for effective treatment against inflammation caused by viral infection [ 144 ].…”