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Indo American Journal of Pharmaceutical Research, 2016 ISSN NO: 2231-6876

ZIKA VIRUS -A LATEST VIRAL PANDEMIC

T. Naga Ravikiran*, T. Nagamounika, Y. Rajendra Prasad

Dept of Pharmaceutical Chemistry, AU College of Pharmaceutical Sciences, Visakhapatnam. Andhra Pradesh, INDIA.

Corresponding author

T. Naga Ravikiran

Dept of Pharmaceutical Chemistry,

AU College of Pharmaceutical Sciences,

Visakhapatnam. Andhra Pradesh, INDIA.

Copy right © 2016 This is an Open Access article distributed under the terms of the Indo American journal of Pharmaceutical

Research, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ARTICLE INFO ABSTRACT

Article history

Received 30/03/2016

Available online

30/06/2016

Keywords

Wolbachia,

Transmission,

RT-PCR assay,

Viremia,Incubation.

Viral infections remain a potential target to the mankind owing to their distinctive structural

and biochemical mechanisms. The viruses will replicate within the host cells and that is the

rationale for their outbreaks as epidemics on the mankind at regular intervals. In the earlier

part of the decade, swine flu massacre killed millions. Later Ebola virus led to death of

millions again And now its time for a novel type of virus, ZIKA VIRUS to ravage and

challenge the mankind. In the current article, the origin, history, etiology, structural features,

life cycle and a scope of various potential treatments were enlisted.

Please cite this article in press as T.Naga Ravikiran et al. Zika Virus -A Latest Viral Pandemic. Indo American Journal of

Pharmaceutical Research.2016:6(06).

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INTRODUCTION

Viruses are tinier and most fatal forms of microbes. The largest of them are smaller than the smallest bacteria. All they have

is a protein coat and a core of genetic material, either RNA or DNA. Unlike bacteria, viruses can't survive without a host. They can

only reproduce by attaching themselves to cells. In most cases, they reprogram the cells to make new viruses until the cells burst and

die. Their unique structural features make them a potential cause of many life-threatening diseases high mortality rates.

Zika virus disease is caused by an RNA virus transmitted to humans through the bite of an infected Aedes mosquitoes,

especially by the Aedesaegypti species.It can also be potentially spread by sex and blood transfusions. The disease may spread from

mother-to-child in the womb and cause microcephaly.

Group: Group IV ((+)ssRNA)

Family: Flaviviridae

Genus: Flavivirus

Species: Zika virus

Fig-1- Mosquito: Aedes Aegypti.

Most people (80%) who are exposed to Zika virus will not get sick. i.e; eighty per cent of infections are asymptomatic.People

with Zika virus disease are characterised by a illness of 2–7 days duration accompanied by mild fever, skin rash (exanthema),

conjunctivitis (red or pink eyes) and headache.There is no vaccine available to prevent and medicine to treat Zika virus infections.The

best form of prevention is protection against mosquito bites. Zika virus had only been known to cause sporadic infections in humans

until 2007.

The first ever Zika virus outbreaks took place in Africa but the most recent findings were found in French, Polynesia, Brazil,

Africa, the Americas, and Asia.

Origin :

It was first identified in monkeys stationed on a tree platform in the Zika Forest in Uganda in 1947.The first human case was

detected in Nigeria in 1954 and further outbreak was reported from the Pacific region in 2007.The latter reported from French

Polynesia in 2013.The current outbreak in Americas Brazil and Colombia (first cases notified in April 2015), is the largest and most

complex Zika outbreak since the Ebola virus was first discovered in 2007. There have been more cases and intra-uterine infectionsand

congenital CNS anomalies (GBS) in this outbreak.

Geographical Spread :

From 2007 to 5 February 2016, Zika viral transmission has been documented in a total of 44 countries and territories (figure

1). This includes 33 countries that reported transmission in between 2015 and 2016. Six countries with indirect evidence of

transmission, and five nations with a history of Zika transmission but no current reported transmission.It has spread between Brazil

Colombia Americas Cape Verde, an island off the coast of West Africa and Asia in 2015 and 2016.

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Fig 2-Spread of Zika virus.

Affected Countries:

Barbados, Bolivia, Brazil, Colombia, the Dominican Republic, Ecuador, El Salvador, French Guiana, Guatemala,

Guadeloupe, Guyana, Haiti, Honduras, Martinique, Mexico, Panama, Paraguay, Puerto Rico, Saint Martin, Suriname, and Venezuela.

Fig 3 Global spread of Zika viral disease among certain parts of Africa and US.

Incubation period :

The incubation period, i.e., the time interval from infection with the virus to onset of symptoms is not clear but is likely to be

a few days.(2-7 days).

Pathogenesis:

The vertebrate hosts of the virus are monkeys and humans.Zika virus (flaviviruses) replicate initially in dendritic cells by

causing infection at the site of inoculation and then will spread to lymph nodes and the bloodstream. Flaviviruses generally replicate in

the cytoplasm, but Zika virus antigens have been found in infected cell nuclei.The most dangerous time is thought to be during the

first trimester of Pregnancy. Infection with the virus appears to be linked to the development of unusually small heads and brain

damage in newborns (microcephaly).

Diagnosis:

Sample: Blood, Saliva, Urine.

Laboratory diagnosis of Zika virus is challenging because of low viremia and cross-reactivity of ZIKV antibodies with other

flaviviruses (including dengue and chikungunya).Biological confirmatiom of the Zika virus infection are made using the following

investigations:

o Antibody-capture enzyme-linked immune sorbent assay (ELISA)

o Serum neutralization test

o Reverse transcriptase polymerase chain reaction (RT-PCR) assay

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Incase of Infants: For infants with Zika virus infection in infants can be detected by using both serologic and molecular assays such as

o RT-PCR

o IgM ELISA

o Plaque reduction neutralization test (PRNT)

In case of pregnant women:

Pregnant women who have travelled to affected areas should be tested between two and twelve weeks after their return from

travel. Women with positive test results for Zika virus infection should have their fetus monitored by ultrasound every three to four

weeks to monitor their anatomy and growth.

Fig 4- Zika virus seen under Micro.

Symptoms:

About 1 in 5 people infected with Zika virus become ill.The most common symptoms of Zika are fever, rashes, joint pain, or

conjunctivitis (red eyes). Other common symptoms include muscle pain and headache. The illness is usually mild with symptoms

lasting for several days to a week after being bitten by an infected mosquito.

Fig – 5-Symptomsof zika virus disease.

The zika infection is more serious as it is associated with two neurological conditions:

Microcephaly Microcephaly is a serious birth defect where a baby’s head circumference is less than expected based on the average for their

age and sex. The condition is usually a result of the failure of the brain to develop properly. This may occur when mother gets

infected during the first trimester of pregnancy.

Zika virus in early stages of pregnancy Zika virus in new born

babies

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Fig – 6-Baby infected with zika virus(Decreased head size)

Guillain-Barrésyndrome Guillain-Barre syndrome (GBS) is a rare disorder where a person’s own immune system damages the nerve cells, causing

muscle weakness and sometimes, paralysis.

Epidemiology of Microcephaly&Guillain-Barré syndrome:

Between 2001 and 2014, an average of 163 microcephaly cases has been recorded in Brazil per year. As on 30 January 2016, the

Brazil Ministry of Health reported 4 783 cases of microcephaly and/or central nervous system (CNS) malformation including 76

deaths.

In July 2015, Brazil reported 76 patients with neurological syndromes, of which 42 (55%) were confirmed as GBS. Among the

confirmed GBS, 26 (62%) had a history of symptoms consistent with Zika virus infection. In addition, 7 patients presenting with

neurologic syndromes were confirmed to be positive for Zika virus infection in November 2015. In 2015, a total of 1708 cases of

GBS were registered nationwide, representing a 19% average increase from the previous year (1439 cases of GBS).

After Brazil, Colombia has been the most affected country. 20297 cases were reported (up to 23 January 2016) since the country’s

first cases were detected in October 2015.In February 2016, the Colombia International Health Regulations (IHR) reported an

average of 242 cases of GBS per year.

Structure of Zika virus: Zika virions are isohedral in shape and they are enveloped, with diameter ranges from18-45 nm. The genome is a positive

strand RNA enclosed in a capsid and surrounded by a membrane.The RNA contains 10,794 nucleotides encoding 3,419 amino acids

and contains envelope proteins E and M.The virus is inactivated by ether, sodium deoxycholate and chloroform.

Fig – 7-Zika virus virions.

Life cycle of Zika virusin host cell: The events in its life cycle involves attachment of Viral envelope protein E to host receptors by clathrin-mediated endocytosis

followed by releasing of RNA genome into the cytoplasm. Then the positive-sense genomic ssRNA is translated into a

polyprotein,and sreplication takes place at the surface of endoplasmic reticulum. The virus complexes at the endoplasmic reticulum, is

transported to the Golgi apparatus and releases new virions by exocytosis.

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Fig-8- Life cycle of Zika virus in its Host cell.

Treatment:

There is no specific treatment for Zika virus infections, patients are advised to take medicine such as acetaminophen or

paracetamol, to relieve fever and pain and any other symptom causing the patient discomfort and antihistaminics for the itching. Do

not take aspirin, products containing aspirin, or other nonsteroidal anti-inflammatory drugs such as ibuprofen.

Fig-9-Treatment of zika virus disease.

Researchers are using certain strains of bacterium Wolbachia (common in mites,spiders,nematodes and insects including

mosquitoes but Aedes mosquitoes doesn’t contain Wolbachia) to spread among mosquitoes to reduce mosquito life span and block

the replication of viruses inside mosquito tissues and finally block the transmission of Zika virus.

At present many research groups around the world are investigating the effect of different Wolbachia infections in major

disease transmitting mosquitoes and we will see results in near future

PREVENTION AND CONTROL OF ZIKA VIRUS: Since Zika virus is spread by infected mosquitoes, the following are some things to reduce the chances of being bitten

Elimination and control of mosquito Avoid allowing stagnant(standing) water in outdoor containers so that they do not become mosquito breeding sites, avoid

accumulating garbage.

Prevention of mosquito bites Personal protection measures to avoid mosquito bites should be applied when staying in risk areas.

Clothing:

Wear long-sleeved shirts and long pants that cover as much of the body as possible.

Indoor Protection:

Sleep under mosquito nets and stay in places with air conditioning or Use physical barriers such as screens, closed doors and

windows.

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Fig – 10-Safety measures to avoid mosquito bites.

Repellent:

Use a repellent with DEET (N, N-diethyl-m-toluamide), permethrin, picaridin (KBR 3023),IR3535 (3-[N-butyl-N-acetyl]-

aminopropionic acid) or oil of lemon eucalyptus [p-menthane 3,8-diol (PMD)] according to the instructions on the product label.

Public awareness about Zika and mosquitoes Peoples should be made aware about the disease and it’s preventive measures. They should take the basic precautions to

protect themselves from the disease

Travel recommendations:

Ttravellers to areas where Zika virus cases have been found are urged to protect themselves from mosquito bites. Pregnant

women considering travel to affected areas may wish to consult their health-care provider prior to travel and after return. They should

also practice personal and household steps to prevent mosquito bites.

Special precautions to pregnant women and women planning to become pregnant: Zika can be spread by a man to his sex partners and from a mother to her fetus during pregnancy. Infection with Zika during

pregnancy is linked to birth defects in babies. Pregnant women/women trying to become pregnant and their male partners should

strictly follow steps to prevent mosquito bites. If male sex partner lives in or travels to an area with Zika, use condoms every time you

have sex, or do not have sex during the pregnancy. If pregnant women who feel they may have been exposed to Zika virus, should

consult with their health-care providers for close monitoring of their pregnancies.

ZIKA VACCINE:

After spotting the similarities between the early stages of Zika, dengue, and Chikungunya, the Bharat Biotech company filed

a patent for two vaccine candidates last year.Bharat Biotech is now ready to begin trialling the potential vaccines in animals within

two weeks.

The first vaccine candidate is a recombinant vaccine, which means it contains Zika DNA, but not the virus itself.The second

potential vaccine is 'inactivated', and contains whole particles of Zika virus that have been tweaked so that they can no longer

replicate or cause infection - but can still trigger an immune response.

Testing these vaccine candidates on animals is expected to take around five months, and after that they will need to be tested

in humans. As the first company to patent potential compounds against Zika, Bharat Biotech is well ahead of the French and Japanese

companies that have just announced they're going to start researching a vaccine.

Response of WHO:

The WHO declared the possible link between Zika and neurological disorders a Public Health Emergency of International

Concern on February 1, 2016. The designation allows the agency to raise funds, coordinate multicountry efforts, and require countries

to share health data relevant to the outbreak with international authorities. The organization called for more research on the virus

(including confirming whether there is a link between Zika and microcephaly), but did not recommended restrictions on travel to

Brazil or other areas with Zika virus transmission. The organization also said pregnant women and women of childbearing age should

have access to "necessary information and materials to reduce risk of exposure."

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CONCLUSION

Zika virus has now emerged as a latest potential challenge to the field of medicine.The Preventive measures and awareness

about spread of the disease can save many a number of people who are directly and indirectly in touch to the infected and

vectors.With an exhaustive study to be made,a lot of research is yet to be done. Diversified areas of research and drug discovery

accounts for the eradication,management and treatment of this viral disease.

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