Targeting Multiple Signal Transduction Pathways of SARS-CoV-2: Approaches to COVID-19 Therapeutic Candidates

Abstract

Due to the complicated pathogenic pathways of coronavirus disease 2019 (COVID-19), related medicinal therapies have remained a clinical challenge. COVID-19 highlights the urgent need to develop mechanistic pathogenic pathways and effective agents for preventing/treating future epidemics. As a result, the destructive pathways of COVID-19 are in the line with clinical symptoms induced by severe acute coronary syndrome (SARS), including lung failure and pneumonia. Accordingly, revealing the exact signaling pathways, including inflammation, oxidative stress, apoptosis, and autophagy, as well as relative representative mediators such as tumor necrosis factor-α (TNF-α), nuclear factor erythroid 2-related factor 2 (Nrf2), Bax/caspases, and Beclin/LC3, respectively, will pave the road for combating COVID-19. Prevailing host factors and multiple steps of SARS-CoV-2 attachment/entry, replication, and assembly/release would be hopeful strategies against COVID-19. This is a comprehensive review of the destructive signaling pathways and host–pathogen interaction of SARS-CoV-2, as well as related therapeutic targets and treatment strategies, including potential natural products-based candidates.

In silico evaluation of food‐derived carotenoids against SARS‐CoV ‐2 drug targets: Crocin is a promising dietary supplement candidate for COVID ‐19

“…Nevertheless, human beings cannot biosynthesize carotenoids, which makes them a group necessary for diet supplementation (Olson & Krinsky, 1995 ). Carotenoids have also been reported to hold significant potential in the development of effective therapeutics for the treatment and prophylaxis of COVID‐19 (Fakhri et al, 2021 ). They attracted special attention due to their involvement in various steps of the viral life cycle and host proteins (Santoyo et al, 2011 ).…”

Potential Therapeutic Use of the Rosemary Diterpene Carnosic Acid for Alzheimer’s Disease, Parkinson’s Disease, and Long-COVID through NRF2 Activation to Counteract the NLRP3 Inflammasome

“…Viral proteins are subject to modification in the intracellular membrane of the ER and contribute to ER stress [ 85 , 86 ]. Replication of SARS-CoV-2 requires a large number of proteins, and after multiple replication cycles, budding leads to viral release from the host cell [ 87 , 88 ].…”

“…To effectively combat the positive feedback loop that contributes to COVID-19 pathogenesis, NRF2 activators have been proposed as a potential therapeutic [ 90 , 91 ]. Until now, however, most proposed therapeutic interventions have focused on overcoming each stress individually rather than the complex positive feedback loop [ 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 ]. For example, dexamethasone is a steroid anti-inflammatory drug, while hydrogen gas or high concentrations of vitamin C are potential free radical scavengers [ 83 , 84 ].…”

Modulation of TLR/NF-κB/NLRP Signaling by Bioactive Phytocompounds: A Promising Strategy to Augment Cancer Chemotherapy and Immunotherapy

“…The considerable volume of reported data proposed that diets rich in phenolic compounds could decrease the incidence of several cancers. Curcumin (Figure 4) is a well-known phytochemical with several important biological activities, including anticarcinogenic, neuroprotective, anti-inflammatory, and anti-SARS-CoV-2 effects (6,13,(80)(81)(82)(83)(84)(85). Curcumin suppressed the proliferation of MHCC97H liver cancer cells in vitro by promoting the formation of intracellular ROS, increasing apoptosis, and activating caspase-3, caspase-8, and TLR4/MyD-88 signaling (86).…”