Anti-Virals:SARS-COV-2 Flashcards
Which tissues are susceptible to attack by the COVID virus (express ACE2 receptors)?
a. Alveolar epithelium, oesophagus, ileum, myocardial cells, kidney, bladder
What is the process for SARS-CIV-2 entry into host cells?
a. Spike protein binds ACE2 receptors on respiratory cells.
b. Host transmembrane serine protease 2 facilitates cell entry
c. Endocytosis
d. Viral replication
e. Viron assembly
f. Budding of virion
What is Remdisivir’s mode of action/mechanism?
b. Requires phosphorylation for activation triphosphate form
c. Competes for incorporation with adenosine triphosphate (ATP)
d. Does not act as classic chain terminator
e. Possible delayed chain termination (similar to entecavir)
Describe what EC50, CC50 and SI (Selectivity index) are?
a. Effective Concentration. The concentration of an antiviral agent at which virus replication is inhibited by 50% in a cell-based assay. Conceptually similar to the MIC (minimum inhibitory concentration) for an antibacterial agent
b. Cytotoxic Concentration. Concentration of an antiviral agent required to kill 50% of cells in uninfected culture
c. Selectivity Index. Ratio between the CC50 and EC50 (CC50/EC50). A higher number signals a theoretically more safe and effective drug
What was the EC50 for Remdisivir? What information do we have about CC50 on remdisvir? What is the SI for remdesivir?
a. EC50: 0.3 µM
b. CC50:> 100 µM (100 M kills only ~20% of cells)
c. SI : (CC50/EC50) > 300
Please describe the safety of Remdisivir, giving a detailed description of its EC50, CC50 and SI (Selectivity index)
a. Requires only a small amount to inhibit 50% viral DNA replication
b. A large amount to kill 50% uninfected host cells
c. The ratio is a large number, indicating a safe drug
The prodrug structure for Remdisivir is given below. Please list the differences and please explain what is the purpose of the differences?
a. It became phosphorylated and turned into an adenosine analog, to “trick” and bind to Rna dependent Rna polymerase, which then incorporates that portion into the viral RNA it was transcribing, to prematurely terminate RNA replication.
