Therapeutic Targeting of Innate Immune Receptors Against SARS-CoV-2 Infection

Abstract

The innate immune system is the first line of host’s defense against invading pathogens. Multiple cellular sensors that detect viral components can induce innate antiviral immune responses. As a result, interferons and pro-inflammatory cytokines are produced which help in the elimination of invading viruses. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to Coronaviridae family, and has a single-stranded, positive-sense RNA genome. It can infect multiple hosts; in humans, it is responsible for the novel coronavirus disease 2019 (COVID-19). Successful, timely, and appropriate detection of SARS-CoV-2 can be very important for the early generation of the immune response. Several drugs that target the innate immune receptors as well as other signaling molecules generated during the innate immune response are currently being investigated in clinical trials. In this review, we summarized the current knowledge of the mechanisms underlying host sensing and innate immune responses against SARS-CoV-2 infection, as well as the role of innate immune receptors in terms of their therapeutic potential against SARS-CoV-2. Moreover, we discussed the drugs undergoing clinical trials and the FDA approved drugs against SARS-CoV-2. This review will help in understanding the interactions between SARS-CoV-2 and innate immune receptors and thus will point towards new dimensions for the development of new therapeutics, which can be beneficial in the current pandemic.

Ectopic expression of SARS-CoV-2 S and ORF-9B proteins alters metabolic profiles and impairs contractile function in cardiomyocytes

“…Viral infection occurs through the binding the surface spike protein (i.e., S protein) with angiotensin-converting enzyme 2 (ACE2), which acts as the primary receptor for the virus. ACE2 is highly expressed in the lungs and also present in large amounts in the heart, causing cardiovascular complications via binding with the S protein of the virus (Hoffmann et al, 2020;Redondo et al, 2021;Farooq et al, 2022). However, the exact mechanisms underlying the cardiovascular complications induced by individual SARS-CoV-2 subunits remain largely unknown.…”

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

“…In animal experiments, TLR2 inhibitor oxPAPC protects against viral pathology in mice [ 15 ], famotidine inhibited expression of TLR3 and downstream TLR3-dependent signaling processes [ 145 ], and aptamers blocking Spike-TLR4 interaction developed by Yang et al exhibited robust anti-inflammatory potential [ 146 ]. There are several potential drugs targeting TLRs under evaluation in clinical trials including resveratrol targeting TLR4, and M5049 targeting TRL7/8 [ 147 ]. Besides TLRs, NLRP3 and inflammasome are also involved in cytokine storm in COVID-19 infections as NLRP3 inflammasome facilitates inflammation by producing IL-1β/18 and causing pyroptosis [ 148 ].…”

Computational Investigation of Selected Spike Protein Mutations in SARS-CoV-2: Delta, Omicron, and Some Circulating Subvariants

“…High-performance computational and mathematical tools have the potential to aid the ongoing efforts that are aimed at identifying appropriate therapeutic targets for these pathogenic variants [6][7][8][9]. In this regard, structure-based computational immunology and bioinformatics-based methods play a critical role in detecting proper drug targets as well as in designing new vaccines [10][11][12][13][14][15]. In prior reports, the author has discussed the time-based structures of various immunologically significant proteins and their structure-function relationships [16][17][18][19].…”