12.2

SARS-COV-2 BIOLOGY

Coronaviruses are single-stranded, positive-sense RNA viruses with the largest

genome of any RNA virus at 26–32 kb [7]. They are enveloped with a diameter of

100–160 nm. They have 6–11 open reading frames (ORFs), the first of which codes

for 16 different non-structural proteins involved in transcription and replication of the

genome. The rest of the genome contains other ORFs that encode the four structural

proteins including the envelope protein (E), the membrane glycoprotein (M), the

nucleocapsid protein (N), and the spike glycoprotein (S) [1,8].

The S protein is composed of two sub-units, S1 and S2, and each S protein is a

trimer of 3 S1/S2 sub-units [7]. It is the S protein that is responsible for host cell

recognition, binding and cell entry. More specifically, it interacts with the angio-

tensin converting enzyme 2 (ACE2) receptor, which is expressed in nearly every

tissue accounting for the virus’s extensive tropism and diverse clinical presentation.

The role of the S1 sub-unit is to bind to the ACE2 receptor via its receptor binding

domain (RBD), while S2 promotes fusion of the viral envelope with the host’s cell

membrane [7].

Upon cell entry, the viral RNA genome is replicated by viral replicase and

translated into viral proteins using host ribosomes. New viruses are then assembled

causing cell lysis allowing them to spread to adjacent cells or to be expelled from

the body via the respiratory tract in the form of droplets or aerosols [9].

There are seven different species of coronavirus known to infect humans–four of

which cause mild infections and three which cause severe infections. The four

milder sub-types are HCoV-NL63, HCoV-229E, HCoV-OC43, and HKU, which

cause mild upper respiratory disease in immunocompetent hosts. Whereas the three

more virulent subtypes are the aforementioned SARS-CoV, MERS-CoV, and, of

course, SARS-CoV-2 [1].

There has been much debate as to the origins of SARS-CoV-2 with the most

likely explanation being that it was derived via zoonotic transfer from a bat. It is

unclear, however, whether it mutated in its animal host prior to transfer, or whether

it underwent natural selection after crossing species [10].

As the pandemic has progressed, several variants of SARS-CoV-2 have emerged

described as either variants of interest, variants of concern, or variants of high

consequence. The criteria outlined by the WHO to define variants of concern are as

follows: increased viral transmissibility, increased disease severity, and a decrease

in the effectiveness of public health measures including among other things, vaccine

effectiveness [11]. Three variants that rapidly gained global attention were B.1.1.7

(first identified in the UK), 501Y.V2 (first identified in South Africa), and P.1 (first

identified in Brazil). All three of these variants acquired the N501Y mutation, which

results in an amino acid substitution at position 501 of the RBD. Two of the variants

have additional amino acid substitutions in the RBD which serve to increase the

binding affinity of the RBD to ACE2 [12].

The B.1.1.7 variant, also known as the alpha variant, was first detected in

England in November 2020 and until recently was the predominant strain in Europe

and North America [11]. However, in December 2020, the B.1.617 strain (or delta)

was discovered in India, which quickly spread around the globe and was designated

COVID-19 vaccines

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