Corona viruses are a
group of related RNA viruses that cause diseases in mammals and birds.
In humans, these
viruses cause respiratory tract infections that can range from mild to lethal.
Mild illnesses include
some cases of the common cold (which is caused also by certain other viruses,
predominantly rhinoviruses), while more lethal varieties can cause SARS, MERS,
and COVID-19.
Symptoms in other species vary: in chickens,
they cause an upper respiratory tract disease, while in cows and pigs they
cause diarrhea. There are as yet no vaccines or antiviral drugs to prevent or
treat human corona virus infections.
They are enveloped
viruses with a positive-sense single-stranded RNA genome and a nucleocapsid of
helical symmetry.
The genome size of
coronaviruses ranges from approximately 26 to 32 kilobases, one of the largest
among RNA viruses. They have characteristic club-shaped spikes that project
from their surface, which in electron micrographs create an image reminiscent
of the solar corona, from which their name derives
Genome
The genome size is one
of the largest among RNA viruses. The genome has a 5′ methylated cap and a 3′
polyadenylated tail.
The genome organization
for a coronavirus is 5′-leader-UTR-replicase/transcriptase-spike (S)-envelope
(E)-membrane (M)-nucleocapsid (N)-3′UTR-poly (A) tail. The open reading frames
1a and 1b, which occupy the first two-thirds of the genome, encode the
replicase/transcriptase polyprotein. The replicase/transcriptase polyprotein
self cleaves to form nonstructural proteins.
Replication cycle
The life cycle of a
coronavirus
Infection begins when
the viral spike (S) glycoprotein attaches to its complementary host cell
receptor. After attachment, a protease of the host cell cleaves and activates
the receptor-attached spike protein. Depending on the host cell protease
available, cleavage and activation allows the virus to enter the host cell by
endocytosis or direct fusion of the viral envelop with the host membrane.
On entry into the host
cell, the virus particle is uncoated, and its genome enters the cell cytoplasm.]
The coronavirus RNA genome has a 5′ methylated cap and a 3′ polyadenylated
tail, which allows the RNA to attach to the host cell's ribosome for
translation. The host ribosome translates the initial overlapping open reading
frame of the virus genome and forms a long polyprotein. The polyprotein has its
own proteases which cleave the polyprotein into multiple nonstructural
proteins.
Replication
A number of the
nonstructural proteins coalesce to form a multi-protein replicase-transcriptase
complex (RTC). The main replicase-transcriptase protein is the RNA-dependent
RNA polymerase (RdRp). It is directly involved in the replication and
transcription of RNA from an RNA strand. The other nonstructural proteins in
the complex assist in the replication and transcription process. The
exoribonuclease nonstructural protein, for instance, provides extra fidelity to
replication by providing a proofreading function which the RNA-dependent RNA
polymerase lacks.
One of the main
functions of the complex is to replicate the viral genome. RdRp directly
mediates the synthesis of negative-sense genomic RNA from the positive-sense
genomic RNA. This is followed by the replication of positive-sense genomic RNA
from the negative-sense genomic RNA. The other important function of the
complex is to transcribe the viral genome. RdRp directly mediates the synthesis
of negative-sense subgenomic RNA molecules from the positive-sense genomic RNA.
This is followed by the transcription of these negative-sense subgenomic RNA
molecules to their corresponding positive-sense mRNAs.
