Coronaviruses and Covid-19

Why do bats harbour so many viruses (2)?

• mammals with deficiency in innate response to viruses

• don’t become sick (suggests immune role in illness)

What are the origins of the coronaviruses (2)?

• 2 step process = bats → intermediate hosts → humans

• e.g. MERS bat → camel → humans

What was the original host for SARS-Cov2?

horseshoe bat

What subfamilies are the human coronaviruses found in (3)?

• found across different subfamilies

• e.g…

  • SARS-CoV found in beta CoV B

  • MERS-CoV found in beta CoV C

What are the stats of SARS-CoV2 (cases, deaths, mortality rate) ?

• 700 million cases

• 7 million deaths

• ~1% mortality rate

How are RNA viruses classified (3)?

• double or single stranded?

• if single stranded - negative or positive sense?

• naked or enveloped?

What does it mean if a virus is enveloped?

more sensitive to degradation and inactivation - shorter lifespan in environment

Which type of ssRNA can be immediately transcribed without special machinery?

positive sense ssRNA

Are dsRNA viruses enveloped or naked?

naked

Are negative sense ssRNA viruses enveloped or naked?

enveloped

Are positive sense ssRNA viruses enveloped or naked?

can be either enveloped or naked

What caused the different waves of covid-19 infections?

different strains

Why did the earlier covid-19 waves have a higher mortality rate?

no immunity in the population

When was the covid-19 vaccine introduced?

december 2020

At what % vaccination is herd immunity achieved for covid-19?

70%

What is anosmia (2)?

• loss of taste

• very specific covid symptom (most symptoms non-specific)

What are the features of the covid-19 virus (3)?

• positive sense ssRNA

• enveloped and spherical

• does NOT replicate via DNA intermediate

What are some of the typical symptoms of covid-19 (4)?

• 88% fever

• 68% dry cough

• 38% fatigue

• 20-30% anosmia / taste loss

What are some of the organ systems and symptoms associated with long covid (6)?

• heart - chest pain, myocardial inflammation

• lungs - cough, abnormal gas exchange

• GI tract - abdominal pain, gut dysbiosis

• neural - fatigue and cognitive impairment, neuroinflamm.

• blood vessels - fatigue, coagulopathy

• repro system - irregular menstruation

What are the potential mechanisms responsible for long covid (5)?

• immune dysregulation

• microbiota dysregulation

• autoimmunity and immune priming

• blood clotting and endothelial abnormalities

• dysfunctional neurological signalling

What is the genome structure of SARS-CoV2 (4)?

• 30k nucleotides (very large for an RNA virus)

• synthesised as long polyprotein - split up by polymerase

• contains RNA dep RNA polymerase

• encodes proof-reading activity - unique

How is SARS-CoV2 unique among RNA viruses?

encodes proof reading activity

Why do viruses often exhibit increased mortality when they initially cross the species barrier (2)?

• no host population immunity

• decrease mortality as adapts to host - good for transmission

What are the 5 approaches to making a vaccine?

• DNA and RNA

• live attenuated

• inactivated

• subunit

• viral vector

What are the pros and cons of RNA and DNA vaccines and what viruses have they been used for (3)?

• pro - easy and quick to design

• cons - never done before covid-19

• covid-19

What are the pros and cons of live attenuated vaccines and what viruses have they been used for (3)?

• pros - stimulates robust immune response without serious disease

• cons - may not be safe for immunocompromised

• MMR, chickenpox

What are the pros and cons of inactivated vaccines and what viruses have they been used for (3)?

• pros - safe as virus is dead, easy to make

• cons - not as effective, some have made disease worse

• polio

What are the pros and cons of subunit vaccines and what viruses have they been used for (3)?

• pros - focuses immune system on key viral component for infection

• cons - may not stimulate strong response, other chemicals may be needed for long lasting protection

• hepatitis B, HPV

What are the pros and cons of viral vector vaccines and what viruses have they been used for (3)?

• pros - live viruses = stronger response than dead viruses / subunits

• cons - important that vector is truly safe and does not stimulate immune response

• ebola

What is the vaccine development process (basic) (3)?

1. target ID, preclinical trials

2. clinical trials:

   • phase 1 - first human trials

   • phase 2 - efficacy in humans

   • phase 3 - evaluation in humans

3. licensure

How does SARS-CoV2 enter host cells?

spike protein binds ACE2

What are the key covid envelope proteins (3)?

• spike protein - binds ACE2 to enter cell

• M protein - shapes virus envelope

• E protein - involved in virus assembly and release

Which 3 companies developed mRNA vaccines for SARS-CoV2?

• BioNTech

• Moderna

• Curevac

How many people over 12 in the UK have received first, second and booster doses of the SARS-CoV2 vaccine (3)?

• first dose - 91%

• second dose - 83%

• booster / third dose - 63%

What treatments have been used against covid-19 (5)?

• dexamethason - only drug to reduce mortality

• remdesivir (polymerase inhibitor)

• paxolid (polymerase and protease inhibitors)

• tocilizumab (anti IL-6 monoclonal antibody)

• sotrovimab (anti spike protein monoclonal antibody)

What is the only drug proven to reduce covid-19 mortality (2)?

• dexamethason (anti-inflammatory steroid)

• for every 100 patients on a ventilator, 12 survive due to dexamthason

What is the impact of using remdesivir against covid-19 (3)?

• only helpful very early in infection

• polymerase inhibitor (repurposed for covid-19)

• decreased recovery time but no impact on mortality

What is the impact of using Molnupiravir against covid-19 (2)?

• polymerase inhibitor

• decreased hospitalisation and death rates

What were identified as interactors of SARS NSP-1 using genome wide screening and what was discovered from this (2)?

• cycophilins (protein family that can bind to immunosuppressants)

• cyclosporin A is a pan-coronavirus inhibitor of human coronaviruses

Which drugs trialled against covid-19 actually led to increased mortality in trials?

chloroquine and hydroxychloroquine

What is the life cycle of covid-19 (6)?

1. attachment and entry

2. uncoating = RNA release

3. translation and RNA replication

4. assembly and maturation

5. packaging at cell surface

6. virion release

What cells does covid-19 enter and how (2)?

• enters respiratory cells

• via ACE2 and TMPRSS2