Medicinal Chemistry and Novel Coronavirus Essay This is a take home Final please be detailed and answer everything according to the word limit, thank you!!

Medicinal Chemistry and Novel Coronavirus Essay This is a take home Final please be detailed and answer everything according to the word limit, thank you!!

The following questions are based on the topics we covered in class. I have provided the relevant manuscripts. However,I encourage you to refer to additional scientific literature to come up with possible answers. You may include scheme(s) and/or figure(s) to illustrate a particular point. Please follow the recommended word limits (including the figure captions). Note that for the purposes of any activity in this class, you are prohibited from posting these questions and accessing the information provided by contract cheating sites (examples include Chegg, Course Hero and many others). Also, note that your answers will be checked for plagiarism.

Question 1: In the class, we will discuss the receptor binding domain (RBD) of COVID-19. A recent research report from the Scripps Research Institute at La Jolla indicates that despite ~80% primary sequence similarity, a neutralizing antibody, CR3022, binds to RBD of SARS-CoV with a much higher affinity than to that of COVID-19 (Kd of ~1 and ~115 nM, respectively). Using the accompanying manuscript as a guide, Yuan et al., Science 2020 (Figs. 1-3), explain this dramatic difference in the binding affinity. (400 words; 25 points).

Question 2: Carbonic anhydrases (CAs), which catalyze the reversible hydration of carbon dioxide to form the bicarbonate anion, were the first Zn2+-dependent metalloenzymes to be characterized. A diverse range of compounds inhibit CAs – acetazolamide is one such compound. Using the accompanying review as a guide, Aoki and Kimura et al (Schemes. 11 and 23), explain the catalytic mechanism of CA and the inhibition mechanism of acetazolamide. (400 words; 25 points)

Question 3: The first-line therapy for the treatment of hypertension and related diseases is the administration of angiotensin-converting enzyme (ACE) inhibitors. Moexipril is a long- acting ACE inhibitor suitable for once- daily administration. Explain the pharmacokinetics of Moexipril. (400 words; 25 points)

Question 4: In the past few years, several orphan GPCRs, for which endogenous ligands have not yet been discovered, have been targeted for therapeutic purpose. Human GPR139 receptor is one such orphan GPCR. Using the accompanying review as a guide, Vedel et al., Basic & Clinical Pharmacology & Toxicology 2020, explain the following – 1) orphan GPCRs; 2) criteria used for “deorphanizing” a GPCR; 3) agonist pharmacophore model described in this review (Fig. 3); 4) proposed agonist binding site (Fig. 4). (400 words; 25 points)