Antivirals

Question 1

Describe the SARS-CoV-2 lifecycle

Answer 1

1. entry - the spike protein on the virus interacts with ACE2 on the host cell which leads to receptor endocytosis - single stranded RNA ends up in the cytoplasm by fusion and fuses with ribosome to make own proteins
2. Replication - virus takes over the cell to produce more viral proteins which involves viral RNA translocation and genome replication
3. Egress - exocytosis-mediated egress to infect nearby host cells

Question 2

Why do viruses need cells

Answer 2

they lack the components needed to replicate RNA e.g. ribosomes

Question 3

What is the name of the section of the spike protein that interacts with ACE2

Answer 3

RBD - receptor binding domain

Question 3

What is the name of the section of the spike protein that interacts with ACE2

Answer 3

RBD - receptor binding domain

Question 4

How do monoclonal antibodies act as antivirals

Answer 4

they specifically inhibit spike protein or glycoprotein

Question 5

What is the name of the antiviral monoclonal antibody used to treat SARS-CoV-2

Answer 5

Sotrovimab

Question 6

What is the main purpose to using Sotrovimab for SARS-CoV-2

Answer 6

it prevents viral entry into host cells this can reduce the risk of hospitalization and death in those with mild/moderate COVID in those with increased risk of severe infection

Question 7

Describe the MoA of REGN-EB3 and mAb114

Answer 7

they are both monoclonal antibodies used for Ebola

they prevent viral entry into host cell by preventing binding of RBD on the glycoprotein to host cell

Question 8

Describe the MoA of Sotrovimab

Answer 8

It binds to the RBD on the virus and prevent binding with ACE2 on host cell

Question 9

How is REGN-EB3 different to mAb114

Answer 9

REGN-EB3 is made up of 3 antibodies which target different parts of the ebola glycoprotein and protein epitope this means it is more efficacious for different variants

Question 10

How do you decide which one to use out of REGN-EB3 and mAb114

Answer 10

depends on availability and emerging info of effectiveness

Question 11

Name 2 nucleotide analogues used for RNA viruses

Answer 11

Remdesivir
Mulnupiravir

Question 12

What enzyme to RNA viruses use to replicate RNA

Answer 12

RNA-dependent RNA polymerase (RdRp)

Question 13

Describe the MoA of Remdesivir

Answer 13

nucleotide analogue
it prevents viral replication

it is metabolised into its active form RTP (remdesivir triphosphate)

RTP is a adenosine analogue which is a nucleoside (a nucleotide without phosphate group)

RdRp incorporates RTP into the RNA strand

RTP replaces ATP which inhibits elongation of the RNA

RdRp stops transcribing RNA and viral RNA becomes defective

Question 14

What is the main purpose of using Remdesivir for SARS-CoV-2

Answer 14

reduces time to recovery in hospital - quicker turnover of patients

Question 15

Describe the MoA of Mulnupiravir

Answer 15

It prevents viral replication

nucleotide analogue (M nucelotide)

The M nucleotide is incorporated into RNA replication sequence by RdRp enzyme instead of C or U nucleotides

A or G are then paired with M nucleotide

This causes mutations in RNA sequence

No functional viral RNA is produced

Question 16

What is the main advantage of prescribing Mulnupiravir

Answer 16

it is an oral drug that is prescribed to high risk patients when symptoms arise this reduced the need for hospitalisation

needs to be given early in infection to be effective