Coronavirus

1) How does corona vVius accomplish maintenance of genomic intergrity given

the large SIze of its genome? 1.5 (2022-2.a) (2021-7.a)
ANS- Coronavirus is a positive-sense single-stranded RNA virus with a genome of about 30
kilobases, which is much larger than most RNA viruses. The maintenance of genomic integrity is
essential for the survival and replication of coronaviruses. To accomplish this, coronaviruses
have evolved several mechanisms that help to maintain their large genomes.

One way that coronaviruses to maintain the genome integrity and avoid deleterious
mutations is through a process called proofreading. During viral replication, the RNA-
dependent RNA polymerase (RdRp) enzyme (3ʹ–5ʹ exoribonuclease) has proofreading
activity. This enzyme can detect and correct errors in the newly synthesized RNA strands,
reducing the mutation rate and maintaining genomic integrity.

Another way that coronaviruses maintain genomic integrity is through a mechanism called
recombination. Recombination occurs when two different viral genomes infect the same cell and
exchange genetic material. This process can lead to the generation of new viral strains with
unique genetic characteristics. However, it can also lead to the formation of defective viral
genomes that cannot replicate or cause disease. To prevent this from happening,
coronaviruses have evolved a mechanism that limits recombination events to within the
same viral genome. This reduces the risk of generating defective viral genomes and helps to
maintain genomic integrity.

The coronavirus genome also contains several cis-acting RNA structures at the 5′ and 3′ ends,
which are essential for RNA replication and transcription. These structures may also help to
protect the viral RNA from degradation by host nucleases.

coronaviruses use a mechanism called transcriptional regulation to control gene expression

and prevent errors during replication. This involves the use of specific sequences within the
viral genome that regulate when and how genes are expressed. By controlling gene expression in
this way, coronaviruses can ensure that each step of replication occurs in a controlled and
coordinated manner, reducing the risk of errors and maintaining genomic integrity.

Finally, coronavirus genome is packaged into a helical nucleocapsid by interacting with the
nucleocapsid protein, which may also contribute to the stability and integrity of the viral
RNA.
2) Explain how subgenomic RNAs are generated during corona virus
infection. 3 (2022-6.b)
ANS- Subgenomic RNAs (sgRNAs) are a class of viral RNAs that are derived from the
genomic RNA of positive-sense RNA viruses, such as coronaviruses. sgRNAs encode for
various structural and accessory proteins that are essential for viral replication and
pathogenesis. The generation of sgRNAs during coronavirus infection involves a complex
process of Discontinuous transcription, in which the viral RNA-dependent RNA
polymerase (RdRp) switches from one template site to another during negative-strand
synthesis. The RdRp recognizes specific sequences, called transcription regulatory
sequences (TRSs), that are located at the 5' end of each gene and at the 3' end of the
genome. The RdRp initiates negative-strand synthesis at the 3' TRS and then jumps to a 5'
TRS of a downstream gene, creating a fusion product that serves as a template for positive-
strand sgRNA synthesis. This process is repeated for each gene, resulting in a nested set of
sgRNAs that share a common 5' leader sequence and a variable 3' trailer sequence.
3) Name the host receptors for SARS-CoV-2. 1 (2020-6.a)
ANS- The novel coronavirus SARS-CoV-2 causes the disease COVID-19, which has become a
global pandemic. To infect host cells, SARS-CoV-2 uses its spike (S) glycoprotein, which binds
to specific receptors on the cell surface. The main receptor for SARS-CoV-2 is angiotensin-
converting enzyme 2 (ACE2) , which is expressed in various tissues, such as the lungs, heart,
kidneys and intestines.
However, ACE2 is not the only receptor for SARS-CoV-2, as the virus can also interact with
other molecules that facilitate its entry into cells. Some of these molecules are transmembrane
protease, serine 2 (TMPRSS2), which cleaves the S protein and activates it for membrane
fusion; cathepsin L, which is another protease that can activate the S protein in endosomes; and
neuropilin-1, which enhances the binding of the S protein to ACE2. By using multiple host
receptors, SARS-CoV-2 can infect a broad range of cell types and tissues, and increase its
chances of transmission and pathogenesis.

4) Name the major host immunogenic consequences caused by SARS-CoV-2. 2

(2020-6.b)
ANS- The novel coronavirus SARS-CoV-2 has caused a global pandemic of COVID-19, a
respiratory disease that can lead to severe complications and death. The virus infects human cells
by binding to the angiotensin-converting enzyme 2 (ACE2) receptor with its spike protein.

SARS-CoV-2, the virus responsible for COVID-19, has several major host immunogenic
consequences. The virus primarily targets the respiratory system and can cause mild to severe
respiratory illness. In severe cases, SARS-CoV-2 can lead to acute respiratory distress
syndrome (ARDS), which is characterized by widespread inflammation in the lungs. This
inflammation can cause damage to lung tissue and make it difficult for oxygen to pass into the
bloodstream. ARDS can be fatal in some cases.

SARS-CoV-2 infection also triggers an immune response in the body. The virus contains
several proteins that can be recognized by the immune system, including the spike protein on its
surface. When the immune system detects these proteins, it produces antibodies to fight off the
virus. However, in some cases, this immune response can be overactive and cause damage to
healthy cells and tissues in the body.

One major consequence of SARS-CoV-2 infection is cytokine release syndrome (CRS). CRS
occurs when the immune system produces large amounts of cytokines, which are signaling
molecules that help regulate the immune response. In some cases, this cytokine release can
become dysregulated and lead to a cytokine storm. This can cause widespread inflammation
throughout the body and lead to organ damage or failure.

Another consequence of SARS-CoV-2 infection is the development of autoantibodies.

Autoantibodies are antibodies that mistakenly target healthy cells and tissues in the body. In
some COVID-19 patients, autoantibodies have been found that target components of the immune
system itself, including interferons and complement proteins. This can impair the ability of the
immune system to fight off infections and increase the risk of severe disease.

Finally, SARS-CoV-2 infection can also lead to long-term effects on the immune system.
Some studies have suggested that COVID-19 patients may experience a reduction in T cell
function, which could increase the risk of reinfection or make it more difficult for the body to
mount an effective immune response to future infections.

In conclusion, SARS-CoV-2 infection can have several major host immunogenic consequences,
including ARDS, cytokine release syndrome, autoantibody production, and long-term effects on
the immune system.

5) To which group of Baltimore classification, does Coronavirus belong? 1

(2020-12.b)
ANS- The Baltimore classification is a system of classifying viruses based on their genome
structure and replication strategy. According to this system, coronaviruses belong to
group IV, which consists of positive-sense single-stranded RNA (+ssRNA) viruses. These
viruses have a genome that can act as a messenger RNA (mRNA) and be directly translated into
proteins by the host cell's ribosomes. Coronaviruses are also enveloped viruses, meaning they
have a lipid membrane derived from the host cell's membrane.

6) Discuss the replication strategy of coronaviruses. 5 (2021-3)

ANS- Coronaviruses are a family of RNA viruses that infect various animals and humans. They
have a distinctive appearance of club-like spikes on their surface, which are used to attach to and
enter host cells. The coronavirus genome is one of the largest among RNA viruses, and it
encodes a complex replication strategy that involves the production of nested subgenomic
RNAs.The replication cycle of coronaviruses can be divided into several steps: entry,
uncoating, translation, replication, assembly and release.

Entry is mediated by the interaction of the viral spike protein with a specific receptor on the
host cell membrane, such as angiotensin-converting enzyme 2 (ACE2) for SARS-CoV-2, the
causative agent of COVID-19.
Uncoating occurs when the viral envelope fuses with the endosomal membrane and releases
the nucleocapsid into the cytoplasm.
Translation involves the recognition of the viral genomic RNA by host ribosomes and the
synthesis of two large polyproteins, pp1a and pp1ab, which are processed by viral proteases into
non-structural proteins (nsps) that form the replication–transcription complex (RTC) .
Replication is initiated by the synthesis of a negative-sense RNA template from the positive-
sense genomic RNA, followed by the generation of positive-sense subgenomic RNAs that have a
common 5′ leader sequence and different 3′ body sequences corresponding to each viral gene .
Assembly occurs in the endoplasmic reticulum–Golgi intermediate compartment (ERGIC),
where the viral envelope proteins are inserted into the membrane and interact with the
nucleocapsids to form immature virions .

Release is achieved by the exocytosis of mature virions through secretory vesicles .