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Drug may be first effective treatment for smallpox
By Rita Rubin, USA TODAY, October 19, 2001
Editorial Comments
The recent threat of bioterrorism in the United States has led to a heightened sense of
awareness of the possible threat of outbreaks of diseases thought to be long ago
eradicated, such as smallpox.
One way in which the government is attempting to prepare for this possibility is to ensure
an adequate stock of smallpox vaccine. According to released estimates, at least 300
million doses of the vaccine would be needed to immunize every American.
The government is also in the process of determining if any currently marketed antiviral
drugs will be of use in treatment. One drug which shows promise is Cidofovir, also
known by the brand name Vistide. This drug would be used, if proven effective, in cases
where infected individuals are unable to obtain a dose of the vaccine within 4 days after
initial contact with the disease. This would be the first antiviral drug that could be able to
combat smallpox. Researchers at the United States Army Medical Research Institute of
Infectious Diseases have reported that Cidofovir is effective in combating some of the
pox diseases, such as monkeypox, in primates.
Structure of Cidofovir
Cidofovir was the original product manufactured by Gilead Sciences to help in combating
cytomegalovirus (CMV) retinitis in AIDS patients. While this disease affects
approximately half of the United States’ population, the body’s immune system is
generally able to fight off outbreaks unless there is an immunodeficiency in the afflicted
individual.
In the event that bioterrorists do attack with the smallpox virus, and the United States has
not been able to stockpile enough doses of the vaccine, Cidofovir would mainly be used
as a backup to aid in treatment of afflicted individuals.
Questions and Answers:
1) What is the IUPAC name of Cidofovir (Vistide)?
(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine
2) What are the common side effects of Cidofovir?
The most serious and commonly reported negative effect of intravenous cidofovir
is kidney toxicity. Your kidney status will be checked the day before you receive an
infusion of cidofovir. If measurements of serum creatinine and protein in your urine
are not within acceptable limits, your physician will either reduce your dose or
discontinue therapy. Hydration with normal saline and administration of oral
probenecid help to reduce the risk of kidney toxicity.
Cidofovir can also cause a fall in the number of white blood cells. This can
increase your risk of developing infections as white blood cells are needed to fight
infections. Cidofovir can also decrease platelets. This can increase your risk of
bleeding or bruising, as platelets are needed to help your blood clot. Your red blood
cells may also decrease which could make you feel tired or short of breath. Blood
tests will be done regularly to check for any changes in these values. If there are any
serious problems, cidofovir will be stopped. Nausea, fever, hair loss and muscle
pain can also occur as a result of cidofovir therapy. If these effects persist and are
bothersome, please call the clinic or discuss this at your next visit.
Some side effects experienced by patients treated with cidofovir may be related to
probenecid. These side effects are rash, nausea, vomiting and fever. Eating food
before taking probenecid helps reduce the risk of nausea and vomiting. Patients who
experience rash or itching are usually given an antihistamine to reduce symptoms.
Inform you doctor if you experience intolerable side effects. (Information can be
found at http://www.tthhivclinic.com/cido.htm)
3) What is an antiviral drug?
Antiviral drugs are medicines that cure or control virus infections.
4) What does the drug Cidofovir bond to in the virus it is attacking?
It bonds to the DNA in the virus. Cidofovir is a modified derivative of cytosine,
which bonds to the DNA through hydrogen bonding during replication. If the
Cidofovir bonds to the DNA twice in a row, then the virus cannot replicate its
DNA anymore. Once the original strands die, the virus will no longer affect the
body. (For the technical explanation see
http://www.rrpf.org/rrpf/therapies/Cidofovir.htm)
5) Use ChemFinder to find the chemical structure, molecular formula, and molecular
weight of Cidofovir.
C8H14N3O6P 279.18886g/mol.
Pertinent Text References
Chapter 15: Alcohols, Diols, and Thiols
Chapter 17: Aldehydes and Ketones
Chapter 20.14: Lactams
Chapter 22: Amines
Chapter 27: DNA