Overview of Coronavirus Variants

thumbnail image: Overview of Coronavirus Variants

There is not longer just one type of SARS-CoV-2 virus. New variants continue to emerge as a result of mutations. This raises the question of whether recovered individuals are still protected from reinfection or whether current vaccines are losing effectiveness. All currently used vaccines prepare our immune system for viral infection by creating antibodies against the spike protein of the original first-wave virus. Most mutations of SARS-CoV-2 do not have a noticeable impact on us, but some do.

To reduce confusion and avoid geographic stigmas, the World Health Organization (WHO) unveiled a new nomenclature for SARS-CoV-2 viral variants in May 2021. Variants that the WHO classifies as "variant of concern" (VOC) or "variant of interest – variant under observation" (VOI) are named after letters of the Greek alphabet. These abbreviations do not replace the scientific names but serve the layperson.

Below, we have a closer look at the variants of concern (VOC) that have been designated by the WHO (as of July 2, 2021). This means variants of the SARS-CoV-2 virus that show (i) an increase in transmissibility or detrimental change in COVID-19 epidemiology, or (ii) an increase in virulence or a change in clinical disease presentation, or (iii) a decrease in effectiveness of public health and social measures or available diagnostics, vaccines, therapeutics.

 

 

1 The SARS-CoV-2 Coronavirus 

SARS-CoV-2SARS-CoV-2 Genome

 

Coronaviruses (CoVs) are a group of enveloped viruses with a positive single-stranded RNA genome. They have the largest RNA viral genome. SARS-CoV-2 contains four structural proteins: the spike, envelope, membrane, and nucleocapsid proteins. CoVs rely on their spike proteins for entering the host cells (see Coronavirus Entering and Replicating in a Host Cell).


In the following we will look at the spike protein. It binds to the host receptor through the receptor-binding domain (RBD) in the S1 subunit, followed by the fusion of the S2 subunit to the host cell membrane (see below).

 

Spike Protein Structural Domains

 

 

2 Coronavirus Variants of Concern (VOC)

WHO Label

Pango Lineage

Spotted in

Number of Muations in Spike

Other Names

alpha

B.1.1.7.

September 2020 in UK

8

GR/501Y.V1

GRY (formerly)

beta

B.1.351

B.1.351.2
B.1.351.3

May 2020 in South Africa

9

GH/501Y.V2

gamma

P.1

P.1.1

P.1.2

November 2020 in Brazil

12

GR/501Y.V3

delta

B.1.617.2

AY.1

AY.2

October 2020 in India

7

G/4478K.V1

 

Swaps or deletions of single amino acids can change the shapes of proteins, and thus, the properties of the virus. Researchers are particularly concerned about mutations in the N-terminal domain of the spike protein (some antibodies target it) and the receptor-binding domain (RBD) of the spike protein (as mentioned earlier, it docks to the ACE2 receptors on human cells and initiates the infection process). Mutations that are particularly worrisome are shown in red in the picture above.


The table below lists which effect selected mutations have for the protein and the virus and in which variants they occure.

 

Spike Mutation

Virus Variant

Effect

Δ69-70 (69-70del)

alpha

may partially interfere with RT-PCR testing,
increases viral infectivity,
leads to immune evasion in immunocompromised patients

Y144Del

alpha

apparently alters the shape of the spike protein so that it can escape some antibodies

K417N

beta, gamma

key epitope for binding neutralizing antibodies => humoral response can be bypassed

L452R

delta

in vitro higher ACE2 receptor affinity, enhanced infectivity, alteration of antigenic properties (affects the binding of certain monoclonal antibodies and could, thus, lead to immune escape)

E484K

alpha (partly), beta, gamma

increased binding to human ACE2 receptor => could be responsible for the virus no longer being recognized by antibodies

N501Y

alpha, beta, gamma

stronger binding affinity to human ACE2 receptor => increased transmissibility

D614G

beta, gamma, delta

more open conformation of the spike protein => better binding to ACE2 receptor protein => higher in vitro infectivity

P681H

alpha

may play a role in spike protein processing
(could modify the processing of the adjacent furin cleavage site)

 

Virus Variant

Effect Compared to Original Virus/Wild-Type

alpha

relative transmissibility about 50 % higher,
mortality probably slightly increased


effectiveness of vaccines only slightly weaker

beta

up to 50 % more infectious,
increased transmissibility,
increased severity,


possible reduction of vaccine effectiveness

gamma

increased transmissibility,
possible increased severity,


possible reduction of vaccine effectiveness

delta

most transmissible form,
increased transmissibility, higher rate of case increase, higher proportion of infected contacts, higher hospitalization rates, probably deadlier

becoming the world's dominant strain


reduction of vaccine effectiveness
vaccine protection from symptomatic disease: BioNTech/Pfizer (1st shot: 33 %; 2nd shot: 88 %), AstraZeneca (1st shot: 33%; 2nd shot: 60 %; probably better protection if 2nd shot with mRNA vaccine), currently no data for Moderna and Johnson & Johnson

 

 

References


Also of Interest

 

 



 

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