PHL-513 Advanced Pharmacology Assignment: COVID-19 and Drugs

This pharmacology assignment, submitted by a student, addresses the relationship between antihypertensive drugs and the risk of COVID-19, summarizing current research and proposing potential alternative therapies. The assignment begins with an analysis of the connection between antihypertensive medications, such as ACE inhibitors and ARBs, and the severity of COVID-19 infections, highlighting the role of ACE-2 in viral entry. It then summarizes a research paper on novel hypertension treatments, focusing on targeting receptors like Mas. Finally, it presents a research proposal investigating the interaction between a drug and a cellular signaling pathway to manage cardiovascular diseases, detailing the experimental design using ELISA to study the interaction between a novel drug and CXCR4, with an expected outcome of visible fluorescence indicating drug-receptor interaction and subsequent pathway modulation. The assignment provides a comprehensive overview of the topic, referencing several relevant research papers.

Running head: PHARMACOLOGY
QUESTION AND ANSWERS
Name of the Student
Name of the University
Author Note

1PHARMACOLOGY
Table of Contents
Answer 1:...................................................................................................................................2
Answer 2:...................................................................................................................................2
Answer 3: Research proposal.....................................................................................................2
Introduction............................................................................................................................3
Literature review........................................................................................................................3
Research design and methods....................................................................................................4
Research design......................................................................................................................4
Method...................................................................................................................................4
Expected outcome..................................................................................................................4
References..................................................................................................................................5

2PHARMACOLOGY
Answer 1: Research papers have stated that there is a link between antihypertensive drugs
and the risk of COVID-19 [1]. Most of the anti-hypertensive drugs include ACE inhibitors
(angiotensin-converting enzyme inhibitors) and ARBs or the angiotensin receptor blocker.
According to the statistical reports, it can be stated that there is a link between the risk of
severe COVID-19 infection and the use of antihypertensive drugs [2]. ACE-2 has been found
to be correlated with the vulnerability of infections which has been mostly given to the
people associated with hypertension associated comorbidities. ACE-2 has been stated to
perform a glycosylation mechanism inside the cells which creates the way for the entry of
COVID-19 into the cells via their spike protein attachment [3]. Thus it can be stated that
ACE-2 is a double-edged sword, for the patients associated with ACE-2 intake for the
prevention of comorbidities of diabetes, hypertension and cardiovascular disease.
Answer 2: In spite of getting success in RAS blockade by ACE inhibitor, angiotensin II
receptor 1 blocker and other blockers, current therapies for cardiovascular diseases are
inadequate [4]. The identification of a novel approach became a primary requirement. The
increased understanding of RAS complexity has been found to lead to novel approaches that
have been found to aim at the up-regulation of the ACE/Mas axis in order to counter the
harmful effects of the ACE AT1R axis. These specific advances have been found to open a
new door to the discovery of drug development based on targeting of the RAS receptors. This
is the overall summary of the research paper which states that targeting Mas is a novel
therapy for the treatment of hypertension.
Answer 3: Research proposal
Interaction between drug and cellular signaling pathway to manage cardiovascular
diseases

3PHARMACOLOGY
Introduction
Cytokine targeting has been found as the most significant therapy associated with the
interaction between SDF-1 and CXCR-34 based cell signaling process using G protein-
coupled receptor. Various drug molecules have been found to bind with the receptors of
many cell signaling pathways in order to neutralize the effect of hypertension in people
suffering from cardiovascular disease. After binding with the receptor, it has been observed
that these drug molecules alter a specific signaling pathway which is associated with the
generation of hypertension in CVD patients. The direct interaction between a signaling
pathway cannot be studied in a mouse model by a laboratory experiment. Thus, the specific
interaction between the drug molecule and the receptor (G protein-coupled receptor) will be
tested in order to gather information about the interaction of the drug with the cellular
signaling pathway. This paper will discuss the interactions between the cell signaling
pathway and the novel drug which targets cytokines.
Literature review
Pieces of literature have stated that cytokine targeting can also play a future role in the
therapy of peripheral vascular disease. This therapy has been found to be associated with
particular chemokine stromal-cell-derived factor-1 (SDF-1 aka CXCL12). This receptor has
been stated to be associated with the GPCR bound cell signaling pathway. Various biological
effects of SDF-1 are mediated by the chemokine receptor CXCR4 has been observed. This
protein receptor is a 352-amino-acid rhodopsin-like transmembrane-specific G protein-
coupled receptor (GPCR). Pieces of evidence have been found to suggest that there is
evidence that the administration of SDF-1 has been found to increase the blood flow and
perfusion process via the recruitment of endothelial progenitor cells (EPCs).

4PHARMACOLOGY
Research design and methods
Research design- Experimental design will be used to study the interaction between the
novel drug and cytokine receptors in controlling hypertension.
Method- The process will follow the use of ELISA (enzyme-linked immunosorbent assay)
in understanding the interaction between CXCR4 and the novel drug. First, the receptor
protein solution will be poured inside the ELISA wells. Then, a quencher attached
fluorophore will be administered in the well so that it binds to the receptor protein at a
different site. No fluorescence signal will be detected at this time. Now, the drug solution
(SDF-1) will be poured in the well and the whole apparatus will be kept still. The reaction
will be allowed to occur for a specific amount of time. After the whole reaction occurs,
fluorescence will be observed if the drug has interacted with the receptor and in turn the
signaling pathway.
Expected outcome: The expected outcome is either a visible fluorescence or no
fluorescence. Since SDF-1 has already been shown to interact with the receptor, it can be
stated that the expected outcome of this experiment will be a visible fluorescence. The
rationale behind this result will be that the quencher molecule which was preventing the
fluorophore to show fluorescence after its initial binding, will be cleaved perfectly by SDF-1
attachment with the receptor. Thus, fluorescence will be shown and it will be proved that the
drug molecule has specifically interacted with the receptor molecule and in turn, it can also
be stated that the drug molecule interacts with the cellular signaling pathway.

5PHARMACOLOGY
References
1, Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at
increased risk for COVID-19 infection?. The Lancet. Respiratory Medicine. 2020 Mar 11.
2. Zheng YY, Ma YT, Zhang JY, Xie X. COVID-19 and the cardiovascular system. Nature
Reviews Cardiology. 2020 Mar 5:1-2.
3. Murthy S, Gomersall CD, Fowler RA. Care for critically ill patients with COVID-19.
Jama. 2020 Jan 1.
4. Meng J, Xiao G, Zhang J, He X, Ou M, Bi J, Yang R, Di W, Wang Z, Li Z, Gao H. Renin-
angiotensin system inhibitors improve the clinical outcomes of COVID-19 patients with
hypertension. Emerging Microbes & Infections. 2020 Jan 1;9(1):757-60.
5. South AM, Tomlinson L, Edmonston D, Hiremath S, Sparks MA. Controversies of renin–
angiotensin system inhibition during the COVID-19 pandemic. Nature Reviews Nephrology.
2020 Apr 3:1-3.
6. Li G, Hu R, Zhang X. Antihypertensive treatment with ACEI/ARB of patients with
COVID-19 complicated by hypertension. Hypertension Research. 2020 Mar 30:1-3.
7. Sparks MA, South A, Welling P, Luther JM, Cohen J, Byrd JB, Burrell LM, Batlle D,
Tomlinson L, Bhalla V, Rheault MN. Sound Science before Quick Judgement Regarding
RAS Blockade in COVID-19. Clinical Journal of the American Society of Nephrology. 2020
Mar 27.
8. Hamdi H, Abdaldayem E. The human-Covid Tango: Connecting the Dots. 2020.