Sudan Journal of Medical Sciences
Volume 18, Issue no. 1, DOI 10.18502/sjms.v18i1.12872
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Commentary

BAY 11-7082: An Anti-inflammatory Drug for
COVID-19
Mohadeseh Nemati1, Fahima Danesh Pouya1, Elmira Roshani Asl1, Yousef
Rasmi1,2*
1Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia,
Iran
2Cellular and Molecular Research Center, Cellular and Molecular Research Medicine Institute,
Urmia University of Medical Sciences, Urmia, Iran
ORCID:
Yousef Rasmi: https://orcid.org/0000-0003-1506-1909

Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new
coronavirus named by the International Committee on Taxonomy of Viruses. COVID-19
patients have high mortality due to respiratory failure from acute respiratory distress
syndrome (ARDS) induced by SARS-CoV-2. The abnormal activation of P21-activated
kinase (PAK1, RAC/CDC42-activated kinase 1) is reported in COVID-19. The PAK1
induces nuclear factor kappa B (NF-κB) activation as well as inflammatory pathways
through its stimulation. BAY 11-7082 {(E) 3-[(4-methylphenyl)-sulfonyl]-2-propenenitrile
is one of the therapies that inhibit inflammation via mentioned signaling pathway,
therefore, we suggest that this drug can potentially be effective in treating COVID-19.

Keywords: BAY 11-7082, COVID-19, PAK1

In late December 2019, a case of unknown pneumonia was described in Wuhan,
People’s Republic of China (PRC) [1]. The “COVID-19” and “severe acute respiratory
syndrome coronavirus 2” (SARS-CoV-2) are the names of the disease induced by novel
coronavirus and the virus that suggested by the World Health Organization (WHO)
and the International Committee on Taxonomy of Viruses, respectively [2] Respiratory
failure from acute respiratory distress syndrome (ARDS) initiated by SARS-CoV-2 is
the leading cause of mortality [3]. P21-activated kinase (PAK1, RAC/CDC42-activated
kinase 1) is the key “pathogenic” kinase. The unusual stimulation of PAK1 induces
several disorders/diseases including viral infections such as COVID-19 and influenza,
and inflammation [4, 5]. In the PAK1 signaling pathway, first, epidermal growth factor
(EGF) stimulates the epidermal growth factor receptor (EGFR) and then activates the
downstream factor, RAS (guanosine-nucleotide-binding protein). This factor is upstream
of PAK1. In the end, PAK1 may activate inflammatory pathways by nuclear factor kappa
B (NF-κB) activation [6]. The NF-κB in most cells’ cytoplasm is bound to an inhibitory
protein, IkB (inhibitory protein of NF-κB complex). It has been revealed that cytokines and

How to cite this article: Mohadeseh Nemati, Fahima Danesh Pouya, Elmira Roshani Asl, Yousef Rasmi* (2023) “BAY 11-7082: An Anti-inflammatory
Drug for COVID-19,” Sudan Journal of Medical Sciences, vol. 18, Issue no. 1, pages 117–120. DOI 10.18502/sjms.v18i1.12872 Page 117

Corresponding Author:

Yousef Rasmi; email:

rasmiy@umsu.ac.ir

Received 26 October 2020

Accepted 19 December 2022

Published 31 March 2023

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Sudan Journal of Medical Sciences Mohadeseh Nemati et al

 EGF, Epidermal growth factor; EGFR, Epidermal growth factor receptor; RAS, Guanosine-nucleotide-binding protein; PAK1, P21 activated kinase 1; 

NF-κB, Nuclear factor kappa B; NO, Nitric oxide; PGE2, Prostaglandin E2; TNF-α, Tumor necrosis factor-alpha; IL-1β, Interleukin-1β;  

IL-18, Interleukin-18; TLR, Toll-like receptor; ROS, Reactive oxygen species; IKK, IκB kinase; IKB, Inhibitory protein of NF-κB complex; 

NLRP3, NLR family pyrin domain containing 3.

Figure 1: Anti-inflammatory effect of BAY 11-7082 on COVID-19.

oxidative stress stimulation lead to the activation of NF-κB. In this stimulation process,
IκB kinase (IKK) phosphorylates IκB, and then it undergoes proteolytic degradation
by the proteasome-dependent pathway [7]. Nuclear translocation of NF-κB elevates the
transcription of several inflammatory factors including chemokines, adhesion molecules,
and cytokines [7, 8]. So, we suggest the treatment of hyperinflammation using exist-
ing, approved therapies to decrease the rising mortality. One of the therapies that
suppress inflammation is BAY 11-7082 (E) 3-[(4-methylphenyl)-sulfonyl]-2-propenenitrile
that inhibits IKK and phosphorylation of IkB [9], so NF-κB remains in an inactive form.
As a result, BAY 11-7082 blocks the expression of tumor necrosis factor-𝛼 (TNF-𝛼),
prostaglandin E2 (PGE2), and nitric oxide (NO), famous inflammatory responses created
by activated NF-𝜅B [10]. The inhibitory effect of BAY-11-7082 is frequently shown as
an investigation test to determine the involvement of IKK, and NF-κB, in a biolog-
ical process, for instance, lung adenocarcinoma in mouse models [11]. Strickson et
al showed that BAY-11-7082 suppresses the activation of IKK indirectly in response
to interleukin-1 or lipopolysaccharide (LPS) in several cells such as T-cell leukemia
and B-cell lymphoma [12]. Also, it is shown that BAY-11-7082 inhibits the NLR family
pyrin domain containing 3 (NLRP3) inflammasome [13]. The inflammasome refers to

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Sudan Journal of Medical Sciences Mohadeseh Nemati et al

assemblies that activate caspase-1 [14], which changes inactive pro-interleukin-1β (pro-
IL-1β) and pro-interleukin-18 (pro-IL-18) into active pro-inflammatory cytokines IL-1β and
IL-18 [15, 16]. These processes are designed in the innate immune cells’ cytoplasm
due to threat signals [14]. The NLRP3 inflammasome is important as it is stimulated by
danger signals, such as viruses, small molecule immune activators, bacteria, purified
microbial products, crystalline or aggregated materials, and components of dying cells
[14]. NLRP3 is expressed in the cytosol of dendritic cells, monocytes, lymphocytes,
neutrophils, osteoblasts, and epithelial cells [17]. So, BAY-11-7082 by inhibition of the
NLRP3 inflammasome prevents the expression of the pro-inflammatory cytokines, IL-
18, and IL-1β in an NFkB-independent mechanism [13]. The investigations reported that
serum IL-1β increased in COVID-19 patients [1]. According to this signaling pathway that
is active in COVID-19 and the inhibitory influence of BAY-11-7082 on this pathway, we
suggest that this drug can potentially be effective in treating COVID-19 (Figure 1).

Competing Interests

None declared.

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	Competing Interests
	References