Above: a diagrammatic section through a coronavirus (CoV). This illustration was based mainly on ViralZone: https://viralzone.expasy.org/30?outline=all_by_species) and, as we shall see, it is a fairly accurate representation according to current knowledge. As illustrated below, the main features are: the large spikes, each consisting of a trimer (three copies bonded together) of the S glycoprotein (S = spike protein). This consists of two functional units (which may be cleaved enzymatically or remain covalently linked according to strain): the S1 head N-terminal) and the S2 tail (C-terminal). These large spikes give the virus its name, since under the electron microscope they resemble a crown of spikes around the virus particle. Note that Coronavirus does not have icosahedral symmetry: it is a helical capsid enclosed in a spheroidal envelope. Nevertheless it is well organised with the spikes and other proteins arranged in a more-or-less definite architecture (Neuman et al. 2006).
Docking to a target cell
Viruses are 'pirates of the cell' so must first enter a host cell before they can replicate. The S1 head contains a receptor-binding domain (RBD) which recognioses and binds to one or more specific receptor molecules in the target cell membrane, in this case the spikes of coranivirus are known to bind to angiotensin-converting enzyme 2 (ACE-2) which is situated in the membrane of certain cells lining the epithelium of the gut and respiratory airways. This enables coronavirus to bind to these cells and infect them, hence coronaviruses can potentially cause respiratory tract and gastrointestinal infections. They may be responsible for about 10 to 20% of common colds, in which the virus infects only the upper respiratory tract (URT) and lacks the necessary virulence to penetrate more deeply into the lower respiratory tract (LRT). However, every so often a strain emerges that can cause LRT, infecting the lungs to cause life-threatening pneumonia in what is known as: severe acute respiratory syndrome (SARS).
In 2003 a SARS CoV1 emerged within the human population which resulted in 8096 cases and 774 deaths: a 9.6% case fatality rate. It is important to understand that case fatality is only the percentage of those diagnosed who die and does not necessarily mean that 9.6% of those infected will die. Similarly an outbreak occurred in the Middle East, the MERS CoV (MERS = Middle-Eastern respiratory syndrome). As of March 2020 there is currently an outbreak of a new strain: SARS CoV2, which having originated in china is now sweeping across other parts of Asian, Europe and America. It is not currently known how deadly this strain will be compared to the current outbreak of influenza, which has likely already killed over 20 000 in the USA alone. The total potential for devastation will depend on the fatality rate and the infectivity of the virus. reported symptoms for this strain typically consist of headaches, cough and difficulty breathing and transmission is by aerosols and contaminated surfaces.
Above:the structure of the coronavirus virion (virus particle). The virion is enveloped and given as about 85 (without spikes?) to 120 nm in diameter. It is approximately spherical. The nucleoprotein (N) binds to the viral single-stranded RNA genome, protecting and packaging it into an (open) helical nucleocapsid. The M (membrane) protein stabilises the structure and determines its geometry (each spike is associated with 4 N and 16 to 25 M proteins in a regular lattice). Each spike consists of a triangular trimer of S glycoprotein and is about 10 nm in diameter at its widest point. There are about 200 to 400 spikes per particle.
Viral RNAs and proteins
- technical breakdown
The genomic RNA of coronavirus is a positive-sense
single-stranded RNA molecule which acts as both the genome and as mRNA
and so is translated directly into viral proteins. The RNA carries a
5' cap and a short 5' leader sequence and poly-A 3' tail to
enable it to be translated like host mRNA by host ribosomes (the
cell's protein factories). There are at least 14 functionsal ORFs,
however, only the open-reading frame (ORF) nearest the 5'-cap gets
translated. The first 5' ORF is ORF1a which is translated into polyprotein
R1a (pp1a). However, sometimes a programmed
ribosomal frameshift occurs which means that a different
message is read and this continues onto the second ORF, ORF1b to
produce a longer R1ab polyprotein (pp1ab). The production of
polyproteins enables the virus to economise on genetic material. Two
viral enzymes (viral proteins PLpro and 3CL) cut the polyproteins into
the separate constituent proteins. The arrangement of the RNA in human
SARS CoV1 is as follows:
ORF1a encodes the following proteins:
ORF1ab encodes the following proteins:
These are the early proteins which establish host cell take-over and begin viral replication. They are non-structural proteins. Their functions are not entirely understood but are roughly as follows:
1. PLpro (proteinase, ns3) and 3CL (protease is
the whole of ns5, which is the also called the main protease)
- cut up the R1a and R1ab polyproteins into their individual proteins.
These enzymes, PLpro and 3CL are being
investigated as potential drug targets.
2. Non-structural protein nsp3 (PLpro) is found in all coronaviruses and is a large multi-domain protein with domains: X, Y and N and two PL-proteinase domains (PLpro) which act as proteinases to cut the polyprotein. Nsp3 binds ADP-ribose and ADP-phosphoribose (or ADP-ribose-1''-P in which the phosphate is on the first carbon of the ribose ring) by its X domain (Johnson et al. 2010). In SARS-CoV nsp3 contains an additional segment, the SARS-unique domain (residues 366-322) consisting of three globular subdomains joined by short linkers (SUD-N, SUD-M and SUD-C) (Johnson et al. 2010)
3. RdRP (ns12) - RNA dependent RNA polymerase, synthesises viral RNAs assisted by other non-structural proteins, such as a helicase (Hel, ns13), that assemble a replication complex. The ssRNA(+) is first copied into a ssRNA(-) template which is then copied into more ss(RNA(+) molecules, both whole genomic RNA and shorter subgenomic RNAs (see below).
4. Non-structural protein ns8 (or nsp8 if we wish to distinguish
the gene from the protein) is a second RdRp which seems to function as
a primase for the first RdRp; ns9 (a single beta-barrel) forms dimers
and binds RNA and interacts with ns8; ns14 is an exonuclease; ns15 is
an endonuclease; ns3 an ADP/ADP-ribose phosphatase; ns16 a ribose
methyl-transferase; ns9b binds lipid. non-structural protein nsp10
(coded for by gene ns10) forms a dodecamer and is thought to act as a
transcription factor (binding to genetic elements to regulate their
expression, Su et al. 2006). Thus, the function of this
protein seems to be in binding RNA.
5. Non-structural proteins nsp1 to nsp16 have some role in the
assembly of a viral replication-transcription complex involved
in viral genome replication, although the exact functions of some of
these proteins is poorly understood.
6. Note that all products of polyprotein 1a are common to
polyprotein 1ab except for ns11 (nsp11) which is only transcribed when
the programmed ribosome frameshift does not occur (Masters 2006).
There are additional ORFs (for the proteins 3a/b,E,M,6,7a/b,8a/b,N,9b,14)
which can not be reached by the ribosomes on the main genomic
RNA (since they are not required early on in infection) but are
translated from shorter subgenomic RNAs which are synthesised
from ssRNA(-) subgenomic templates. These subgenomic negative-strand
templates are thought to be synthesised by an unusual process called discontinuous
transcription in which the 5' leader is copied first and then
the appropriate 3' body sequence for the ORF being transcribed. In
SARS CoV-1 this generates the following subgenomic RNAs (the genomic
RNA is mRNA1):
1. mRNA2 encoding for S (spike) protein
2. mRNA3 encodes proteins 3a/3b
3. mRNA4 encodes E (envelope protein)
4. mRNA5 encodes M (membrane protein)
5. mRNA6 encodes protein 6
5. mRNA7 encodes proteins 7a/7b
6. mRNA8 encodes proteins 8a/8b
7. mRNA9 encodes proteins N/9b; N is the nucleoprotein
8. mRNA10? encodes protein 14?
Note that these are essentially structural proteins involved in
virion assembly, though the functions of some are not understood. Note
also that a single subgenomic RNA can encode two different proteins in
an either-or manner; this is the case for mRNAs 2, 5, 6 and 7. For
example mRNA 7 can be translated to give the protein N or the protein
9b. This occurs by a process called leaky scanning. In leaky
scanning the ribosome sometimes skips a weak START codon for the first
protein to locate a second START codon (which may be in a different
reading frame) for the second protein. This enables the virus to
economise on genetic material.
SARS CoV-2 (2019) or COVID-19 has some differences (see
In particular there is no 8/8b RNA, no 3b and a possible additional
subgenomic RNA for ORF10 which hypothetically encodes an unknown
You can view the genetic sequence of SARS CoV-2 (2019) as
isolated from China on the NCBI database: https://www.ncbi.nlm.nih.gov/nuccore/MN908947.3?report=fasta.
It will be informative to see whether or not other countries have
mutated variants. Phylogenetic analysis reveals a close relationship
to the coronavirus of bats.
Target cell entry
After attaching to the target cell (which may involve additional steps) the cell is tricked into endocytosing the virus obstructing its surface receptor: the virus and the receptor it is bound to will be enclosed in a membranous vesicle inside the cell. The cell will then attempt to digest and recycle the contents of the vesicle that becomes an endo-lysosomal vacuole. The endo-lysosome can be thought of as the 'stomach' or waste disposal center of the cell. The S2 subunit anchors the spike in the viral envelope, but, as we shall see, also has a critical function for the virus. The host cell will use a suite of enzymes, high acidity and an arsenal of molecular weapons to attempt to destroy the enclosed virus and recycle its components. However, when conditions begin to change inside the vacuole the S2 mechanism of the spike is activated. Specifically, part of the S2 (called the fusion peptide) is exposed by a conformational change in S1/S2 when S1 binds its target receptor (ACE-2) and S2 subsequently gets cleaved inside the endo-lysosome which activate the S2 fusion mechanism.
Antibodies against the S protein have been
shown to be effective in blocking invasion by the virion. This
represents a potential for vaccine development whereby a vaccine
consisting of fragments of S may be able to raise specific antibodies
that block the function of the spikes.
Each S2 contributes a long alpha-helix, the three helices of each trimer forming an anchoring rod. However S2 also contains the fusion peptide (FP) which rapidly unfolds to insert into the host cell (endo-lysomal) membrane (it unfolds to a length of about 20 nm to reach the target membrane). The FP then brings about fusion of the viral envelope with the containing host cell membrane, allowing the contents of the virus particle (virion) to escape into the host cell's cytosol.The subsequent steps in the mechanism is not fully understood in the case of coranavirus but is better studied in HIV and influenza. In HIV membrane fusion is brought about by a 'hairpin-loop' mechanism: the fusion peptide unfolds and penetrates the target cell membrane then the fusion protein bends about a hinge to pull the two membranes close together to overcome their mutual electroststic repulsion and allow the membrane phosopholipids to rearrange into an open pore or channel with positive curvature across the two membranes to form an expanding fusion pore.
Thus, the spikes are important for target cell attachment and viral entry and therefore determine in large part the hosts and range of tissues the virus can infect. Coronaviruses cause zoonoses, or diseases of animals, but have a broad host range. This enables them to occasionally jump from one animal species to another, including humans. Ideally, it is not in the best interests of a virus to destroy its host or to raise an immune response and viruses that are well adapted to their hosts may be able to steel the resources they need without causing significant disease symptoms. Viruses seem to be at their most deadly, however, when they have just jumped to a new host species with which they are not highly compatible. This accounts for the severity of SARS pandemics.
Commandeering host cell machinery
When a virus enters a host cell it must first evade destruction by the host cell's defenses, ideally by evading detection. It must also deactivate any alarm systems within the cell, both to prevent the cell mounting its own defenses and to prevent the cell alerting others, including cells of the immune system. this is its first priority, then it must take control of cell machinery, in particular the cell's protein and nucleotide factories to make more copies of itself.
To achieve these aims, the virus must carry its own 'computer program' in the form of genetic material with which to reprogram the host cell. The genetic material of coronavirus consists of RNA rather than DNA and the coronavirus has the largest RNA genome of any known virus at 27 to 32 kb. This is important: larger viruses generally utilise DNA to store their program since it is a more stable medium than RNA. However, smaller viruses can cope with RNA which due to its lability mutates faster than DNA which gives RNA viruses a very high rate of mutation and hence of evolution.
Packaging such a large RNA genome poses problems. Many RNA viruses are helical, with many copies of a nucleoprotein (N) binding to the RNA to protect, stabilise and package it into a helix of ribonucleoprotein which often forms a definite rod-shaped ribonucleoprotein particle (RNP). In the case of influenza, its modest-sized 13.5 kb genome is packaged into 8 separate ribonucleoprotein particles: the genome consists of 8 molecules of RNA. The larger genome of coronavirus consists of a single RNA molecule which appears to package into a fairly loose and open helix which fills most of the virus particle, but is concentrated in the outer region just below the envelope.
The architecture of SARS CoV, as currently understood, has been well illustrated by David S. Goodsell who kindly contributed his work to the Protein Data Bank (http://pdb101.rcsb.org/sci-art/goodsell-gallery/coronavirus):
Illustration by David S. Goodsell, RCSB Protein Data Bank; doi:
10.2210/rcsb_pdb/goodsell-gallery-019. David Goddsell's biomolecular illustrations are
truly fabulous! This illustration of coronavirus (shown embedded in
host mucus) represents the structure according to the state of our
knowledge. Note the folding and twisting of the helical RNA-protein
particle (ribonucleoprotein particle) shown in magenta inside the
The genetic material of coronavirus consists of ssRNA(+), that is
single-stranded RNA of the positive sense. Positive RNA has the same
genetic code as the mRNA (negative sense is complementary) and can be
directly translated by host ribosomes into proteins. In this way two
polyproteins, R1a and R1ab, are synthesised and cut-up by viral
enzymes into early proteins involved in the replication of viral RNA.
Some of the proteins produced have an unknown function but the virus
must gain control of the cell first, subverting its machinery for its
own purposes. this is often accompanied by an attempt to shut down
synthesis of host cell proteins and make viral proteins instead and
also involves evasion of host cell defenses. At least protein N enters
with the viral RNA and this may have a role in overriding the host
cell's systems as it can bind DNA.
Once secure, the virus modifies the internal membranes of the
cell (the endoplasmic reticulum, Golgi complex and associated
membranes) to create a virus factory. Later genes are transcribed and
translated (from subgenomic RNAs) to produce structural proteins and
assembly of virus particles takes place. The host cell membranes act
as a scaffold for virus assembly and are also thought to shield the
dsRNA that the virus produces from detection by host cell systems
(such as protein kinase R, PKR). The host cell does not generally form
dsRNA (double-stranded RNA) but many viruses have to, as an
intermediate in genome replication, as when coronavirus copies
plus-strands of RNA into minus-strands and full genome-sized negative
strands into new plus-stranded genomes.
Assembly, packaging and escape of progeny from the host cell
Once the various viral components, genomic RNA (gRNA) and structural proteins have been manufactured, they must be packaged into new virions. This requires the N protein to oligomerise (that is for N subunits to bond together into higher order structures) whilst binding to gRNA and assembling the ribonucleoprotein helix. The N protein contains two RNA-binding domains: the N-terminal domain (NTD) and the C-terminal domain (CTD). The CTD also contains a dimerisation domain that binds to another N protein molecule. In some betacoronaviruses, such as MHV (mouse hepatitis virus, not in the same family as human hepatitis viruses) and BCoV (bovine coronavirus) which belong to the A lineage of betacoronaviruses there is a genome packaging signal (PS) consisting of about 95 nucleotides about 20.3 kb from the 5' end of the gRNA. This puts the PS within the gene coding for nsp15 (a subunit of the replicase-transcriptase complex needed for viral nucleic acid synthesis). This is predicted to fold as a stem-loop in the gRNA secondary structure (due to hydrogen-bonding RNAs will fold into more complex shapes that can have functional significance). Additionally, the CTD of N contains a linker connecting it to the N3 domain which binds to M. Thus, N binds gRNA and also binds to the viral envelope protein M, allowing the structure of the virion to assemble. Additionally the linker between the CTD and NTD of N binds to nsp3 (a subunit of the viral RNA replicase). Viruses lacking a functional PS will also package subgenomic RNA (sgRNA) into the virion, that is they can no longer specifically recognise the gRNA for packaging (Kuo et al. 2016). SARS-CoV belongs to the B group of betacoronaviruses and does not have a PS homologue but it has been shown to have a functionally equivalent domain in the N CTD (Kuo et al. 2016).
The N-protein not only dimerises but forms tetramers and octamers, at least in the crystal structure, and this positions the two RNA binding domains of each N monomer along a double groove in which the genomic RNA (gRNA) is thought to sit (on the outside of the ribonucleoproteins) (Chen et al. 2007). The negatively charged phosphate backbone of the gRNA is predicted to sit in teh grrove with the bases projecting outwards but protected by aromatic residue side-chains that intercalate between them. The virus needs to package its large gRNA into a very small volume and it has been suggested that to do this the gRNA must be supercoiled and thus the ribonucleoprotein complex must be a very flexible structure that twists and folds on itself. Single-stranded RNA can adopt more stable conformations than double-stranded DNA, which is more rigid molecule. Cryo-electron microscopy reveals material in the centre of the virus, though it is likely (and generally considered) that the genome is most compact near the periphery: packing nucleotides in the very central part of a virus imposes problems since the RNA would have to be folded very tightly and entropy opposes such conformations (that is they require more energy to achieve) and a limit is reached before the nucleic acid will break when bent too tightly. It is possible that some of the material inside the virion could be additional viral proteins.
The final structure has a well-organised architecture with the base of each spike (S-trimer) surrounded by four N subunits. The S and M proteins interact as do the M and N proteins resulting in a final stoichiometry ranging from 1S-trimer : 16M : 4 N to 1S-trimer : 25M : 4N. The viral components thus have a well-organised architecture and arrange into fairly precise lattices (Neuman et al., 2006).
The virus progeny must eventually escape from the infected cell before it is destroyed and as it's resources are consumed. The virus needs to find new host cells to feed upon. The spikes are embedded in an envelope, consisting of a phosopholipid bilayer, stolen from the internal membrane systems of the host cell the virus was produced in and escaped from. The virus acquires its envelope before escaping from the host cell (in some viruses an envelope is acquired when escaping across the plasma membrane by budding) when budding from the ER-Golgi compartment of the cell. In the case of coronavirus, escape if by exocytosis of the enveloped virion. The mechanism of budding in coronavirus does not use the usual ESCRT machinery of the host cell, it is ESCRT-independent budding. This is where the E protein likely plays a role. This protein is a pentamer, five sub-units spanning the viral envelope with a central channel between them: it is a cation channel, allowing positive ions to flow across it when open; it likely acts as a viroporin. In ESCRT-independent budding (see ViralZone: https://viralzone.expasy.org/5898) the membrane of the host cell compartment encloses around the virion with the help of viral ion channels called viroporins which allow an influx of positive ions to occur at the point where the membrane must fuse. This influx of ions depolarises this region of the membrane, removing electrostatic repulsion and so lowering the energy barrier for membrane fusion. (Function of E-protein: Ruch and Machamer 2012; Nieto-Torres et al. 2014; Surya et al. 2018).
In the diagram of coronavirus above, which is based on the structure as represented in the ViralZone database, E pentamers are shown at one end of the virion. This represents the basal end where it separated from the host cell membranes. This process also helps the final packing of the genetic material by helping to close the virion into a spheroid. Prior to budding the virion is assembled as a two-dimensional array, using the host membrane as a scaffold. In particular, the M protein organises this region of the membrane; host membrane proteins are excluded and M interacts with N (this interaction is shown by a conformational change in the model as the M protein tail contacts the N protein directly beneath the viral envelope. M also interacts with S and these interactions ensure the correct spacing and stoichiometry of these components: the virion is well ordered. Other proteins possibly incorporate into the viral envelope, such as 3a and 7a and some strains of coronavirus also have additional smaller spikes formed of hemagluttinin-esterase (HE) which may assist attachment to host cells but also degrades carbohydrate chains in the extracellular matrix to allow escaping virus particles to diffuse freely and reach new targets.
Protein 3a is an envelope protein that possibly forms a tetramer that may function as an ion channel and may have a role in budding (Lu et al. 2006). The respective roles of E and 3a in budding is not clear.
The N protein packages the RNA genome. Analysis of the crystal structure of the N protein suggests that the N units form N-N dimers, about 4.5 nm in length, which may then interact in pairs to form tetramers and octamers and thus forming a helix of stacked tetramers. Spiral grooves of basic subunits exposed on the outer surface of these assemblies are thought to accommodate the viral RNA which may sit in the grooves with its phosphate backbone inside and aromatic amino acid residues are thought to intercalate with the RNA bases to protect them.
The coronavirus family (Coronaviridae)
All the SARS strains of coronavirus are Betacoronaviruses. Alphacoronaviruses may cause less serious infections in humans and may also infect animals. Gammacoronaviruses have been found in birds and Beluga Whales and Deltacoronaviruses are also found in birds. Less closely related is the Torovirus subfamily. Torovirus infects animals and humans and may cause fecal-oral gatroenteritis in humans.
The toroviruses are interesting due to their unusual morphology. Although their genetic sequences differ substantially from the coronavirus subfamily, their general genetic architecture, replication and transcription are sufficiently similar for them to be included in the Coronaviridae family. Torovirus packages its 28 kb genome into a more compact and distinct helix than in coronavirus. This helix is rod-shaped inside the host cell but assumes its curved toroidal shape upon budding. This torus-like ribonucleoprotein particle gives the virus its name and also determines its shape. Shape in toroviruses varies, but the envelope generally fits quite tightly around the ribonucleoprotein torus such that the final virion is generally a biconcave disc or C-shaped (both shown in section above, in both plan and side-view). At least some strains also have the smaller HE spikes (shown in the diagram above on the right side of the virion only, though distributed throughout when present). The virion is a similar size as for coronavirus (about 120 nm diameter).
The ssRNA(+) genome of torovirus encodes the following (likely depending on strain):
Again a ribosomal frameshift allows the synthesis of the 1ab polyprotein (pp1a) in addition to the 1a polyprotein (pp1a) and these polyproteins are again processed to form non-structural proteins involve din replication, such as the viral polymerase (rdRp). Four subgenomic RNAs encode the following:
1) mRNA-1 encodes S
2) mRNA-2 encodes M
3) mRNA-3 encodes HE
4) mRNA-4 encodes N
There is also a possible 5th subgenomic RNA of unknown function.
Coronavirus evolution - FAQ: Is a vaccine possible?
Coronaviruses are indeed one of the agents responsible for common colds and no vaccine exists for the common cold, so can one vaccinate against (or develop antivirals to) SARS CoV-2? One might argues that if one can not vaccinate against the common cold then one can not vaccinate against SARS CoV. However, there are many more strains of virus causing common colds than the serious SARS strains and so we do not need a vaccine that works against all strains. Yes coronaviruses mutate rapidly, but so does influenza and any vaccine would need updating at frequent intervals. However, it is potentially possible to develop a vaccine against the more serious strains particularly by targeting an essential system of the virus that evolves relatively slowly.
When a protein is absolutely essential to a virus, then the key component of that protein generally evolves slowly, since most mutations would render the virus ineffective and so there is less 'room for flexible change'. Clearly the immune system can combat SARS CoV and it is known that antibodies are produced that target the S glycoprotein. Certain sequences on the S protein are essential for its function, such as binding to the host receptor and the fusion peptide mechanism. In viruses in general, these essential sequences can change and evolve but generally more slowly than many other regions of the same protein - they are relatively conserved sequences. A vaccine could potentially consist of the necessary conserved peptides (assuming they fold into the correct shape and can be administered without adverse side-effects). A requirement is that the region being targeted is exposed on the viral surface so that antibodies generated by a vaccine can reach the target. For less accessible targets drugs with an appropriate delivery system can potentially be developed. Another potential antiviral target are the polyprotein-processing enzymes (the equivalent have been useful targets in HIV therapy, see https://en.wikipedia.org/wiki/Discovery_and_development_of_HIV-protease_inhibitors for a brief overview).
The importance of finding sequences that are both relatively conserved and critical to viral function and accessible to drug action can not be overstated. SARS CoV-2 is already mutating rapidly with the genetic sequence of strains differing between isolates from different countries (https://doi.org/10.1038/s41422-020-0290-0). Thus, although a vaccine is possible to develop an effective vaccine is no easy task.. the virus is closely related to strain RaTG13 from bats. There are signs that the virus has undergone both positive (enhancing beneficial traits) and negative (purifying opr removing harmful traits) natural selection since jumping to a human host (Longxian et al. 2020). The receptor-binding domain (RBD) of S1 has diverged considerably from RaTG13 which may possibly be the result of genetic recombination between RaTG13 and another unidentified coronavirus (Longxian et al. 2020). there is evidence that the virus is already evolving in response to antiviral drugs (see EDITORIAL - Virus against virus: a potential treatment for 2019-nCov(SARS-CoV-2) and other RNA viruses. Cell Research (2020) 30:189–190;
With more research into the molecular systems of SARS CoV, further potential drug targets may emerge. For example, the viral polymerases or other viral RNA processing enzymes, as long as the target is sufficiently different from host proteins so as to limit side-effects. Targeted delivery to infected cells could potentially reduce drug toxicity.
Additional modes of therapy may include using an engineered virus to combat SARS CoV-2 (https://doi.org/10.1038/s41422-020-0290-0) by using the CRISPR/Cas13d system, a technique developed from the natural ability of bacteria to develop immunity to their own viruses, to rapidly generate modified adeno-associated virus particles that target and destroy CoV RNA. These modified virus particles could carry manufactured guide RNAs and the RNA-editing enzyme CAS13d. The guide RNAs would locate CoV RNA and then CAS13d would destroy them.
FAQ - Was SARS CoV-2 manufactured?
Not necessarily. It is certainly closely related to a bat strain and has and is currently undergoing rapid natural evolution. However, it has been suggested that its ability to bind the human receptor and hence be an effective parasite in humans was the result of recombination with an unknown strain. If true, then this could have been a natural event, e.g. if the bat strain infected the same individual as a human CoV strain, or vice versa. However, it could also be the result of laboratory manufacture.
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Created on 17 March 2020
Updated: 18 Mar 2020, 19 Mar 2020, 21/3/2020