NEW VARIANTS OF

SARS-CoV2

TBILISI STATE MEDICAL UNIVERSITY

BY- PRIYANKA BHOWMIK
SEM-10
GROUP-15
INTRODUCTIO
N
SARS-CoV-2, the virus that causes
COVID-19, has had a major impact on
human health globally; infecting a large
number of people; causing severe
disease and associated long-term
health sequelae; resulting in death and
excess mortality, especially among
older and vulnerable populations;
interrupting routine healthcare
services; disruptions to travel, trade,
education and many other societal
functions; and more broadly having a
negative impact on peoples physical
and mental health.
CURRENT DASHBOARD
• Globally, as of 3:44pm CET, 19 March 2021, there have
been 121,464,666 confirmed cases of COVID-19,
including 2,684,093 deaths, reported to WHO. As of 17 March 2021, a
total of 364,184,603 vaccine doses have been administered.
• In India, from 3 January 2020 to 3:44pm CET, 19 March 2021, there have
been 11,514,331 confirmed cases of COVID-19 with 159,370 deaths,
reported to WHO. As of 15 March 2021, a total of 34,859,345 vaccine
doses have been administered.
• In Georgia, from 3 January 2020 to 3:44pm CET, 19 March 2021, there
have been 276,796 confirmed cases of COVID-19 with 3,683 deaths,
reported to WHO.
Coronavirus Variants and Mutations
• Each coronavirus contains nearly 30,000 letters of RNA. This 
genetic information allows the virus to infect cells and hijack them to
make new viruses.
• As an infected cell builds new coronaviruses, it occasionally makes
tiny copying errors called mutations. Scientists can track mutations as
they are passed down through a lineage, which is a branch of the viral
family tree.
 Diagram of the
CORONAVIRUS
GENOME
What is a variant?
• A group of coronaviruses that share the same inherited set of distinctive
mutations is called a variant.
• Viral variants are new versions of a virus that arise as a result of small changes
in its genetic code.
• What is strain?
•  If enough mutations accumulate in a lineage, the viruses may evolve clear-cut
differences in how they function. These lineages come to be known as strains.
Covid-19 is caused by a coronavirus strain known as SARS-CoV-2.
• Over the course of the pandemic, a number of variants of SARS-CoV-2 have
arisen. Some of them are raising worries that they may draw out the
pandemic or make vaccines less effective.
What gave rise to the new variants?
• Most RNA viruses lack a molecular proofreader, a protein that checks
for mistakes and corrects them, so they “accumulate more typos
more quickly,” said Ms. Steinberg of the Feinstein Institutes for
Medical Research. Coronaviruses, including the one that causes
Covid-19, do have one and so tend to mutate more slowly.
• Having a proofreader also makes coronaviruses three times the size of
most RNA viruses, said Vineet Menachery, a coronavirus expert at the
University of Texas Medical Branch. That gives them an advantage, he
added: “It means they can encode more proteins to antagonize the
immune response.”
• Some scientists believe the new variants, which have a large number
of mutations, arose in Covid-19 patients whose weakened immune
systems allowed the virus to reproduce over long periods of time—
giving it plenty of opportunities to accumulate multiple mutations.
• High rates of infection in the population also add to the risk that new,
potentially more harmful variants will emerge, infectious-disease
experts say. And with the virus spreading quickly around the world,
experts say they expect to see more variants crop up.
Is it usual to forms variants?
• When virus replicate in a host, they face the challenge of duplicating
their genetic material.  For many viruses, their offspring often contain
errors. These errors are referred to as mutations, and viruses with
these mutations are called variants.
• “It’s just like natural selection, like evolution,” said Bettie Steinberg, a
virologist and provost at Northwell Health’s Feinstein Institutes for
Medical Research.
• Like all viruses, the coronavirus that has caused the deadly
pandemic keeps changing in small ways as it passes from one person
to another.
• But some mutations trigger changes in the spike protein that the virus
uses to latch on to and enter human cells - these variants could
potentially be more infectious, cause more severe disease or evade
vaccines. Such 
variants have been already identified in UK, South Africa and Brazil.
•  WHO is tracking different mutations and variants around the world
through genomic sequencing.
 Mutations that may help the coronavirus
spread
Lineage Mutation Status

B.1 D614G Appeared in early 2020 and spread around the world.

Several N501Y A defining mutation in several lineages, including B.1.1.7, B.1.351 and P.1. Helps the
virus bind more tightly to human cells.

Several E484K or “Eek” Appears in several lineages. May help the virus avoid some kinds of antibodies.

Several K417 Appears in several lineages, including B.1.351 and P.1. May help the virus bind more
tightly to cells.

Several L452R Increasingly common in California, but not yet shown to be more infectious.

Several Q677 Found in seven U.S. lineages, but not yet shown to be more infectious.
Can we control cropping up of new
variants?

• The potential for virus mutation increases with the frequency of

human and animal infections. Therefore, reducing transmission of
SARS-CoV-2 by using established disease control methods as well as
avoiding introductions to animal populations, are critical aspects to
the global strategy to reduce the occurrence of mutations that have
negative public health implications.
DISTRIBUTION of SARS-COV2
VARIANTS of Concern
• Coronaviruses that appear to be more infectious than other
circulating coronaviruses.
• The UK COVID-19 variant has now spread to  94 countries worldwide,
including the United States, where there have been more than 3,000
confirmed cases.
• The South African variant is circulating in 48 countries around the
world including the United States.
• Brazilian variant of Covid-19 has spread to 26 countries.
(Updated: March 19, 2021)
 Date of earliest_B.1.1.7 detected Schematic map showing the date of the
first sequence sample date in each
country containing the lineage. Darker
countries have earlier first sample dates.

Map of B.1.1.7 sequence counts

Map showing the logged number of
sequences of the variant in each
country. Countries with more
sequences are shown in darker colours.
2021-03-19
Date of earliest_B.1.351 detected
Schematic map showing
the date of the first
sequence sample date in
each country containing
the lineage. Darker
countries have earlier first
sample dates.

Map of B.1.351 sequence counts

Map showing the logged

number of sequences of the
variant in each country.
Countries with more
sequences are shown in
darker colours.

2021-03-19
Date of earliest_P.1 detected
Schematic map showing the date
of the first sequence sample date
in each country containing the
lineage. Darker countries have
earlier first sample dates.

 Map of P.1 sequence counts

Map showing the logged

number of sequences of the
variant in each country.
Countries with more
sequences are shown in
darker colours.

2021-03-19
Variant First First Characteristic mutations (protein: No. of current No. of current No. of
designation identifica identifica mutation) sequence- sequence- countries
tion tion Date confirmed cases confirmed cases with
Location United States Worldwide sequence
s

B.1.1.7 United Sep 2020 ORF1ab: T1001I, A1708D, I2230T, 4616 170940 94
(20I/501Y.V1) Kingdom del3675–3677 SGF

S: del69–70 HV, del144 Y, N501Y,

A570D, D614G, P681H, T761I, S982A,
D1118H

ORF8: Q27stop, R52I, Y73C

N: D3L, S235F
B.1.351 South Oct 2020 ORF1ab: K1655N 77 4087 48
(20H/501Y.V2) Africa

E: P71L
N: T205I
S:K417N, E484K, N501Y, D614G,
A701V (Updated: March 19, 2021)

Abbreviations: del = deletion; E = envelope protein; N = nucleocapsid protein; ORF = open reading frame; S = spike protein.
Variant First First Characteristic mutations No. of current No. of current No. of
designation identificati identificati (protein: mutation) sequence- sequence- countries
on on Date confirmed cases confirmed with
Location United States cases sequences
Worldwide

P.1 Brazil Jan 2021 ORF1ab: F681L, I760T, 39 744 26

(20J/501Y.V3) S1188L, K1795Q, del3675–
3677 SGF, E5662D

S: L18F, T20N, P26S, D138Y,

R190S, K417T, E484K,
N501Y, start
highlightD614Gend highlight,
H655Y, T1027I

ORF3a: C174G
ORF8: E92K
ORF9: Q77E
ORF14: V49L
N: P80R (Updated: March 19, 2021)
Abbreviations: del = deletion; E = envelope protein; N = nucleocapsid protein; ORF = open reading frame; S = spike protein .
The 'UK variant' — B.1.1.7
• A new lineage of the SARS-CoV-2 virus (named B.1.1.7) was identified from genomic
sequencing of samples from patients with covid-19 in the south east of England in early
October 2020.
• In December 2020, Public Health England identified this virus as a variant of concern (VOC-
202012/1).
• On 14 December 2020, authorities of the United Kingdom reported to WHO a variant
referred to by the United Kingdom as SARS-CoV-2 VOC 202012/01 (Variant of Concern, year
2020, month 12, variant 01).
• During December this new variant spread from the south east to London and the rest of the
UK, with three quarters of infections being attributable to the new variant by 31 December
2020.
• Since then, the prevalence of VOC-202012/1 has been observed to be increasing in both
Europe and the US.
• This variant contains 23 nucleotide substitutions and is not
phylogenetically related to the SARS-CoV-2 virus circulating in the United
Kingdom at the time the variant was detected.
• Preliminary epidemiologic, modelling, phylogenetic and clinical findings
suggest that SARS-CoV-2 VOC 202012/01 has increased transmissibility.
However, preliminary analyses also indicate that there is no change in
disease severity (as measured by length of hospitalization and 28-day
case fatality), or occurrence of reinfection between variant cases
compared to other SARS-CoV-2 viruses circulating in the United Kingdom.
• After examining the evidence surrounding the new variant, the UK
New and Emerging Respiratory Virus Threats Advisory Group
(NERVTAG) concluded it "had moderate confidence" the variant is
substantially more infectious than other variants.
• The variant of concern, in addition to being more transmissible,
seems to be more lethal. This is expect to be associated with changes
in its phenotypic properties because of multiple genetic mutations.
• Thus infection with the variant "is associated with an increased risk of
death" compared with non B.1.1.7 viruses.
• The most likely increase in mortality risk with the new variant is close
to the middle of this range, at around 64%, say the researchers.
• This may be the result of one of the mutations in the spike protein of
the variant — a mutation called "N501Y”.
• N501Y is associated with increased binding of the virus to a receptor
found on the surface on many of our cells, called "ACE2". This could
mean the variant is even more efficient at entering our cells.
• Another of the mutations in the VOC 202012/01 variant, the deletion
at position 69/70del was found to affect the performance of some
diagnostic PCR assays with an S gene target. Most PCR assays in use
worldwide will use multiple targets and therefore the impact of the
variant on diagnostics is not anticipated to be significant.
KEY MUTATIONS IN B.1.1.7
• Mutations in the spike protein include:
• — N501Y, which helps the virus latch on more tightly to human cells.
But the mutation is not likely to help the virus evade current vaccines.
• — P681H, which may help infected cells create new spike proteins
more efficiently.
• — The H69–V70 and Y144/145 deletions, which alter the shape of the
spike and may help it evade some antibodies.
 It takes three spike proteins to form one spike, so
each mutation appears in three places:

Key mutations in
Key mutations in
the B.1.1.7 spike
the B.1.1.7 spike
(top view)
The 'South African variant' — B.1.351
• This variant was first detected in Nelson Mandela Bay, South Africa, in October 2020.
• On 18 December, national authorities in South Africa announced the detection of a new
variant of SARS-CoV-2 that is rapidly spreading in three provinces of South Africa.
• South Africa has named this variant 501Y.V2, because of a N501Y mutation.
• In the week beginning 16 November, routine sequencing by South African health authorities
found that this new SARS-CoV-2 variant has largely replaced other SARS-CoV-2 viruses
circulating in the Eastern Cape, Western Cape, and KwaZulu-Natal provinces. 
• Similar to the UK variant, it quickly outcompeted other SARS-CoV-2 variants in South Africa.
It now accounts for more than 90 per cent of SARS-CoV-2 samples in South Africa that
undergo genetic sequencing.
• While SARS-CoV-2 VOC 202012/01 from the UK also has the N501Y mutation, phylogenetic
analysis has shown that 501Y.V2 from South Africa are different virus variants.
• While genomic data highlighted that the 501.V2 variant rapidly
displaced other lineages circulating in South Africa, and preliminary
studies suggest the variant is associated with a higher viral load, which
may suggest potential for increased transmissibility, this, as well as
other factors that influence transmissibility, are subject of further
investigation. 
•  Moreover, at this stage, there is no clear evidence of the new variant
being associated with more severe disease or worse outcomes. Further
investigations are needed to understand the impact on transmission,
clinical severity of infection, laboratory diagnostics, therapeutics,
vaccines, or public health preventive measures. 
• The authorities in the affected countries are conducting epidemiological
and virological investigations to further assess the transmissibility, severity,
risk of reinfection and antibody response to new variants. As one of the
mutations (N501Y) – found in both the SARS-CoV-2 VOC 202012/01 and
501Y.V2 variants – is in the viral S gene which lies in the receptor binding
domain, where the virus binds to the host cell and where vaccine-induced
antibodies bind to the virus.
• The authorities are investigating the neutralization activity of sera from
recovered and vaccinated patients against these variants to determine if
there is any impact on vaccine performance. These studies are ongoing.
• It also contains several other concerning mutations. Two of these,
called "E484K" and "K417N", are bad news for our immune system.
They can reduce how well our antibodies bind to the virus (though
this is also based on preprint data awaiting peer review).
• But there's no evidence yet to suggest the South African variant is
more deadly than the original variants.
• it appears to have a higher viral load and is therefore more
transmissible. This variant shares similarities with the English and
Brazilian variants in that it contains both the N501Y and E484K spike
protein mutations.
KEY MUTATIONS IN B.1.351

• Mutations near the tip of the spike protein include:

• — N501Y, which helps the virus latch on more tightly to human cells.
This mutation also appears in the B.1.1.7 and P.1 lineages.
• — K417N, which also helps the virus bind more tightly to human
cells.
• — E484K, which may help the virus evade some kinds of antibodies.
 Key mutations in
the B.1.351 spike
Mutations in the
(top view)
B.1.351
LINEAGE
The 'Brazilian variant' — P.1
• This variant, known as P.1 or VOC202101/02 in the UK
• This variant was first detected in Japan in a group of Brazilian travellers in
January 2021.
• It's now highly prevalent in the Brazilian state of Amazonas, and has been
detected in countries including South Korea and the United States.
• Like the South African variant, the Brazilian variant has the spike protein 
mutations N501Y, E484K and K417N (as well as numerous other mutations).
• While there's no evidence this variant causes more severe disease, there's 
concern it has facilitated a wave of reinfections in Manaus, the largest city in
Amazonas, which was thought to have reached "herd immunity" in October
last year.
• The UK’s New and Emerging Respiratory Virus Threats Advisory Group
(Nervtag) said people who had antibodies after a bout of Covid-19
might not have natural immunity.
•  P1 “contains 17 unique amino acid changes, three deletions, four
synonymous mutations and one 4nt insertion”. All the variants have a
number of mutations. The key anxiety is that P1 has three that are
causing concern – K417T, E484K, and N501Y.
• This is the mutation thought to give the variants some ability to
escape the vaccines. It decreases their efficacy, although it does not
knock them out.
KEY MUTATIONS IN P.1
• Key mutations in the spike protein are similar to those in the B.1.351
lineage, although they arose independently:
• — N501Y, which helps the virus latch on more tightly to human cells.
This mutation also appears in the B.1.1.7 and B.1.351 lineages.
• — K417T, which is the same site as the K417N mutation in the
B.1.351 lineage. It may also help the virus latch on tighter.
• — E484K, which may help the virus evade some kinds of antibodies.
• Vaccines
• One study showed reduced plasma neutralising activity against SARS-CoV-2 variants encoding E484K, N501Y, or
K417N:E484K:N501Y (the combination present in B.1.351) in a cohort of 20 volunteers who received either the
Moderna (n=12) or Pfizer (n=6) vaccine, 8 weeks after the second dose.
• There was a 1-3 fold decrease in neutralising activity against E484K, a 1.3-2.5 fold decrease in neutralising
activity against N501Y, and a 1.1-3 fold decrease in neutralising activity against K417N:E484K:N501Y.
• Several studies have shown a low to moderate reduction in neutralisation activity against B.1.351 in immune
sera from Moderna and Pfizer vaccinees. The clinical impact of this reduction remains unclear.
• In one study, the loss of neutralisation activity in the immune sera of vaccinees was principally attributed to
E484K.
• It is possible that the P.1 variant will show similar patterns of antigenic escape to vaccine-acquired immunity
as the B1.351 variant, due to similar genomic profiles, in particular the presence of E484K. However, there
remains no direct evidence for antigenic escape from vaccine-acquired immunity in the P.1 variant.
• There is some evidence to suggest that variants containing the E484K change show antigenic escape from
individual monoclonal antibodies.
Do the current vaccines work against the
Brazilian, English, and South African
variants?
• The three main vaccines—Pfizer BioNTech, Moderna,and Oxford
AstraZeneca—all target the spike protein of the virus, where these
variants have mutations. Researchers are still fairly confident,
however, that the vaccines will work against them—although they are
not sure whether protection could be reduced—because the spike
protein is so large that many mutations would be needed to
completely escape. Studies are now underway to test whether the
vaccines are effective against these new variants.
Could the virus still mutate to escape the
vaccines?
• In an interview with The BMJ,5 Andrew Pollard, who leads the Oxford
vaccine clinical trials, said the crucial period will be when lots of
people are vaccinated, as this will put the virus under a lot of
pressure. “Whenthat happens some viruses just can’t compete against
that immunity. Will it mutate instead? With this coronavirus we don’t
know the answer to that question yet, and that’s why surveillance is
going to be critical in the year ahead to make sure that we’re not in a
position where, at the point of population immunity, the virus escapes.
And if it does, we need to know that, so that we can redesign the
vaccines,” Pollard said. He added that the Pfizer, Moderna, and Oxford
vaccines are “relatively straightforward to redesign for a new variant.”
Other variants in the news
Lineage Variant name Status

B.1.427, B.1.429 CAL.20C Common in California, but not yet shown to be more infectious.
Carries the L452R mutation.

B.1.526 ___ Spreading in New York. One version carries the E484K mutation,

another carries S477N.
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