SARS-CoV2 variants: a primer

SARS-CoV2 variants a primer Thomas R. Unnasch, PhD, FASTMH

What is Cov 2?

• A member of the coronavirus family

Coronaviruses • Common viral infections of animals • Four coronaviruses cause colds in humans • Three coronaviruses cause serious infections in humans • Severe Acute Respiratory Syndrome -1 (SARS-1) virus • Middle Eastern Respiratory Syndrome (MERS) • Severe Acute Respiratory Syndrome -2 virus (SARS-CoV2) – cause of 2019 Coronavirus Disease (COVID19)

Structure of SARS-CoV2

Why does the spike protein get all the attention?

• Encodes the receptor binding domain (RBD) • Part of the virus that binds to the cell surface protein that lets the virus enter the cell (Angiotensin-converting enzyme 2, or he Ace-2 receptor)

• Major target of immune response to the virus • 1273 Amino Acids in length (180 kDa)

Natural selection in viruses • Mutation • Selection • Founder effects

Mutation in RNA viruses • Mistakes in replication process • • • •

RNA Polymerases are error prone SARS-Cov2 – 1x10-6 per site per cycle Influenza 3 x 10-5 per site per cycle One site change at a time

• Recombination • Potential for re-assorting combinations of existing mutations

Types of mutations • Transitions – purine replaces purine (A to G or G to A) or pyrimidine replaces pyrimidine (C to T or T to C) • Transversions purine replaces pyrimidine or vice versa • Deletions or insertions

The genetic code • 64 different codons (groups of three nucleotides that specify a particular amino acid) • 3 stop codons • 61 codons for amino acids • 20 amino acids • Redundancy in the genetic code • e.g. leucine coded for by CTT, CTC, CTA, CTG, TTA, TTG

Classification of mutations • Silent (synonomous) mutations • Missense mutations • Mutations of concern • Labelled by amino acid position, identity of the progenitor residue and the mutant reside • E484K – a mutation which changes the 484th amino acid in the spike protein from a glutamic acid (E) to a lysine (K)

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Selection of mutants • Host range • Virulence • Infectivity • Immune system avoidance • Drug resistance