Virology B Term Paper - Reagan Mutimba

REAGAN MUTIMBA
SHBI/01093/2017
VIROLOGY B TERM
PAPER
Discuss what the status of development to date by industry/research institutions is with
regards to antiviral strategies against enveloped pathogenic viruses in our quest to get
these viruses under control.
Many emerging chronic viral diseases are caused by enveloped viruses. These viruses have
developed efficient strategies to escape host immune control, therefore treatment options
are limited. Enveloped viruses are viruses that contain a lipid membrane. Majority of the
enveloped viruses are pathogenic. Examples of these viruses include HIV and Influenza.
Several industries and research institutions have developed antiviral strategies of getting
these viruses under control due to the adverse effects they have on human beings. Some of
these strategies are as discussed below.
1. Targeting the cell entry of enveloped Viruses.
Inhibition of viral infections can be done therapeutically. This can be achieved through
targeting the various steps involved in the cell cycle of a virus. These steps include cell entry,
virus replication and release of newly formed virions.
Before a virus a virus enters a cell, it must first attach to the cell membrane receptors
through their envelope proteins. These viral envelop proteins serve to mediate specific
attachment to the cell and for membrane fusion. When attachment is inhibited, the virus
cannot penetrate the cell. There are various inhibitors that research institutions have used
to prevent entry of these viruses into the cell. These include the following two:
Inhibitors targeting envelope proteins
Envelope proteins mediate specific attachment to the cell and membrane fusion. Fusion of
enveloped viruses with host cell is a key step in viral infectivity. Interference with this
process can lead to highly effective antivirals.
Antibodies
Neutralizing monoclonal antibodies have been developed and this has served as a promising
antiviral strategy. These antibodies block host cell receptors by binding to specific epitopes
on the receptor molecules.
2. Development of Synthetic Anti-lipopolysaccharide Peptides
These peptides inhibit viral infections by binding to heparin sulfate on the cell surface.
Heparin Sulfate is a cell surface molecule that acts as a docking site for a variety of
enveloped viruses. Synthetic Anti-Lipopolysaccharide peptide is positively charged and binds
to the negatively charged heparin sulfate, and neutralizes its charges. By binding to heparin
sulfate, which is a receptor for certain enveloped viruses, no attachment occurs hence the
viruses cannot enter the cell.
3. Activity of Hydrogen Sulphide

Hydrogen sulphide is a colorless gas that is toxic and flammable at high concentration. It is
an important endogenous mediator that has been recently discovered in its role of
cytoprotective and anti- inflammatory responses against enveloped RNA viruses. It
modulates the inflammatory response and viral replication of these viruses by use of a
compound donor GYY4137. This compound decreases expression of viral proteins and
mRNA and this suggests inhibition of an early step of replication. GYY4137 acts by inhibiting
production of pro-inflammatory cytokines and chemokines. When viruses enter into
respiratory endothelial cells, they trigger production of pro-inflammatory cytokines and
chemokines such as Interleukins and Interferons. Cytokines and chemokines serve to recruit
and activate primary immune cells causing them to express receptors that promote immune
cell migration from circulation. These cells damage respiratory endothelial cells and amplify
the inflammatory response. Inflammation is necessary for successful viral clearance. These
enveloped viruses try to survive by triggering production of pro-inflammatory cytokines,
however, their action is inhibited by GYY4137. Therefore, inhibition of pro-inflammatory
response is an important prospect in antiviral interventions.
4. Inhibition of Viral Uncoating
Membrane uncoating describes the separation of internal virion components from the viral
membrane so that the internal components can enter the cell. In this case the viral genome
from the capsid is released to the cell after disintegration. This process is mediated by viral
or host enzymes. Advancements have been made to inhibit the uncoating step of viral
replication by developing antiviral drugs that target this step. These drugs block the proteins
responsible for uncoating on the capsid, such as the ion channel proteins, which play an
important role in capsid disintegration. They also inhibit enzymes such as neuraminidase
which mediate the uncoating process.
5. Inhibition of Viral enzymes
There are viral enzymes which play a critical role in the replication cycle of a virus. These
enzymes include Reverse transcriptase, viral integrases and viral proteases. Reverse
transcriptase is the enzyme responsible for DNA synthesis while Viral proteases mediate
completion of viral maturation.
Viral integrases are specific for retroviruses. They mediate covalent integration of viral
genetic information into the host cell genome through DNA cleavage and joining reactions.
Inhibition of this enzyme ensures no integration of viral genetic information occurs.
Reverse transcriptase transcribes single stranded DNA from single stranded RNA chain. In
order for viruses to replicate, they use reverse transcriptase to make DNA copies of their
RNA genome. When this enzyme is inhibited, DNA synthesis does not take place and the
virus is not able to replicate.
Proteases are other enzymes that are used by some viruses such as HIV to cleave precursor
long protein chains into individual proteins. This will allow the completion of viral
maturation since the proteins and viral RNA come together to form virion particles which
can exit the cell.
Antiviral drugs have been developed to inhibit the action of these enzymes so that
replication and viral maturation does not occur.

6. Targeting Delivery of Antiviral RNA molecules.
This can be achieved through gene therapy. In somatic gene therapy, where therapeutically
effective genes are introduced within a sub set of patient cells, delivery of antiviral principle
is ensured. Gene therapeutic approaches can be used to eliminate infected cells, to render
cells resistant to infections or to induce cells to release antiviral peptides in the
environment.
7. Targeted Silencing of Viral Gene expression
This is achieved through specific degradation of viral mRNA or by blocking its translation to
protein. It is mediated by Antisense RNAs or ribozymes. Successful inhibition of virus
replications by expression of antisense RNAs has been demonstrated for a large number of
viruses including HIV and Influenza viruses.
References
I. Handbook of Experimental Pharmacology 189 (Antiviral Strategies)- Hans George
Krauslich and Ralf Barten Schlager.
II. Journal of Antimicrobial Chemotherapy
III. Journal of Infectious Diseases
(https://academic.oup.com/jid/article/205/11/1654/847201)
IV. Nature Scientific Reports (https://www.nature.com/articles/srep41029)

V. Boundless Microbiology (https://courses.lumenlearning.com/boundless-
microbiology/chapter/antiviral-drugs/ )
VI. Biology Libretexts (https://bio.libretexts.org/Bookshelves/Microbiology/Book

%3A_Microbiology_(Boundless)/13%3A_Antimicrobial_Drugs/13.7%3A_Antiviral_Drugs/13.
7A%3A_Antiviral_Agents_that_Prevent_Virus_Uncoating_or_Release)

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REAGAN MUTIMBA

these viruses under control.

these strategies are as discussed below.

1. Targeting the cell entry of enveloped Viruses.

virus replication and release of newly formed virions.

process can lead to highly effective antivirals.

on the receptor molecules.

2. Development of Synthetic Anti-lipopolysaccharide Peptides

enveloped viruses. Synthetic Anti-Lipopolysaccharide peptide is positively charged and binds

viruses cannot enter the cell.

3. Activity of Hydrogen Sulphide

cytoprotective and anti- inflammatory responses against enveloped RNA viruses. It

production of pro-inflammatory cytokines and chemokines. When viruses enter into

respiratory endothelial cells, they trigger production of pro-inflammatory cytokines and

enveloped viruses try to survive by triggering production of pro-inflammatory cytokines,

however, their action is inhibited by GYY4137. Therefore, inhibition of pro-inflammatory

response is an important prospect in antiviral interventions.

4. Inhibition of Viral Uncoating

which mediate the uncoating process.

5. Inhibition of Viral enzymes

completion of viral maturation.

Inhibition of this enzyme ensures no integration of viral genetic information occurs.

virus is not able to replicate.

can exit the cell.

replication and viral maturation does not occur.

cells resistant to infections or to induce cells to release antiviral peptides in the

7. Targeted Silencing of Viral Gene expression

protein. It is mediated by Antisense RNAs or ribozymes. Successful inhibition of virus

viruses including HIV and Influenza viruses.

I. Handbook of Experimental Pharmacology 189 (Antiviral Strategies)- Hans George

Krauslich and Ralf Barten Schlager.

II. Journal of Antimicrobial Chemotherapy

III. Journal of Infectious Diseases

IV. Nature Scientific Reports (https://www.nature.com/articles/srep41029)

VI. Biology Libretexts (https://bio.libretexts.org/Bookshelves/Microbiology/Book

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