Strategies Tackling Viral Replication and Inflammatory Pathways as Early Pharmacological Treatment for SARS-CoV-2 Infection: Any Potential Role for Ketoprofen Lysine Salt?

Abstract

COVID-19 is an infective disease resulting in widespread respiratory and non-respiratory symptoms prompted by SARS-CoV-2 infection. Interaction between SARS-CoV-2 and host cell receptors prompts activation of pro-inflammatory pathways which are involved in epithelial and endothelial damage mechanisms even after viral clearance. Since inflammation has been recognized as a critical step in COVID-19, anti-inflammatory therapies, including both steroids and non-steroids as well as cytokine inhibitors, have been proposed. Early treatment of COVID-19 has the potential to affect the clinical course of the disease regardless of underlying comorbid conditions. Non-steroidal anti-inflammatory drugs (NSAIDs), which are widely used for symptomatic relief of upper airway infections, became the mainstay of early phase treatment of COVID-19. In this review, we discuss the current evidence for using NSAIDs in early phases of SARS-CoV-2 infection with focus on ketoprofen lysine salt based on its pharmacodynamic and pharmacokinetic features.

Modulation of innate immunity related genes resulting in prophylactic antimicrobial and antiviral properties

“…In this regard, the viral propagation has been reported to be promoted by oxidative stress and several viruses ( e.g., SARS-CoV-2 [ 123 ]), once entered into the host cells, can trigger reactive oxygen species (ROS) and, subsequently, COX-2 activation [ 124 ]. Indeed, COX-2 levels have been reported as increased in response to RSV [ 125 ], FLU-A [ 126 ] and SARS-CoV-2 [ 127 ]. Here, RNAseq data analyses obtained from Caco-2-infected cells show diminished levels of COX-2 and COX-3 in those Solution-3-pre-treated cells (COX2: Fold Changes − 2.8; p-value, 6.35E-11; COX3: Fold Changes − 4.06; p-value, 3.34E-16; Additional file 8 ).…”

Potential Anti-SARS-CoV-2 Molecular Strategies

“…Moreover, even after the virus has been eradicated, the previous SARS-CoV-2 interaction with host cell receptors and consequent activation of pro-inflammatory pathways may still be responsible for endothelial and epithelial damage mechanisms. In this context, anti-inflammatory treatments, such as steroidal and non-steroidal drugs, as well as cytokine inhibitors, have been suggested in the treatment of COVID-19 patients, since inflammation treatment has been identified as a crucial step in the recovery process [7]. The complications observed in COVID-19 patients are numerous, especially in cases of the more severe forms of the diseases.…”

“…By screening 171 candidates obtained from the DrugBank database (http://www.drugbank.ca/ accessed on 17 February 2023), other in silico studies identified possible organic triazole compounds such as bemcentinib, and bisoctrizole, as M pro inhibitors whose pharmacokinetic characteristics were also evaluated, and their complex stability and conformation were examined using molecular dynamics simulation [11]. Non-steroidal anti-inflammatory drugs, which are frequently used to treat upper airway infections symptomatically, are of crucial importance when administered in the early stages of SARS-CoV-2 infection and, in this context, ketoprofen lysine salt is a non-steroidal anti-inflammatory drug which was suggested to offer notable benefits in early COVID-19 therapy, based on the pharmacodynamic and pharmacokinetic characteristics of this drug [7].…”

Extracellular Vesicle-Based SARS-CoV-2 Vaccine

“…It needs a parasite to enter a host cell, and then uses the functions of that cell to multiply itself with the following steps. (i) Absorption: Viruses must first bind to receptors on animal cell surfaces [ 35 , 36 , 37 ]. In SARS-CoV-2, this life cycle begins when the surface-protruding S protein binds to the receptor of ACE2, an enzyme protein on the cell surface.…”