Computer-aided or computational drug design is fast gaining prominence in many drug discovery campaigns. This approach leverages on chemical and biological information about ligands and/or biological targets to design potential drug candidates whereby the biological and physical properties of the target are studied and a prediction is made of the sorts of chemicals that might ût in to an active site. This streamlines the drug discovery and development, avoiding a large population of inactive compounds to save money, time and resources.

Today, there are many drugs which owe their discovery to the application of computational method of drug design. One of such is Dorzolamide, a carbonic anhydrase inhibitor used for the management of glaucoma. It was the first drug which resulted from structure base computational drug design approach introduced in 1995 by Merck.
Computer-aided drug design as a tool in drug development is being applied in the repositioning of known drugs for a different therapeutic use. Computational drug repositioning involves repurposing a known drug for new therapeutic indication, using computer technology. In other words, it involves finding new therapeutic use for already existing drugs.

Examples of repositioned drugs

There are many examples of drugs successfully repositioned. A typical example is the phosphodiesterase inhibitor, Sildenafil, sold as Viagra, which was initially developed for treating pulmonary arterial hypertension (angina) but later repositioned for the treatment of erectile dysfunction. Another well-known example is Thalidomide developed by the German drug company, Chemie Grunenthal in 1957. It was primarily prescribed as a sedative or hypnotic. Afterwards, it was used against nausea and to alleviate morning sickness in pregnant women. Due to its teratogenic effects as seen in the malformation of limbs in infants, it was withdrawn from the market in 1961 and later repositioned for the treatment of certain cancers (multiple myeloma) and in complication of leprosy.

It is worthy of note that drug repositioning may be achieved with or without computational design tools. In the past, some drugs formerly indicated for the treatment of certain ailments or used for entirely different purposes were discovered serendipitously or deliberately repositioned to be useful for other therapeutic indications. An example is the sulphur mustard which was used as a biological weapon during the second world war, but later repositioned without the use of computer-assisted drug modelling, serving as the template for the development of the nitrogen mustards (DNA alkylating agents) such as Melphalan used in cancer chemotherapy.

For a drug to be successfully repositioned, adequate information on the biological activity of the drug and/or target and its involvement in the pathology of the disease condition must be known. The process of gathering such functional information of the biological target is called “target validation” in pharmaceutical industry parlance.

The application of computational drug repositioning as an alternative approach in drug development  has been made possible by increase identification of molecular targets, elucidation of the 3D structures by X- ray crystallography and Nuclear magnetic resonance (NMR), availability of commercial, private or public databases (for biological targets and ligands), and availability of computer-aided drug design software.

Approaches to computer-aided drug design

Depending on the availability of structural information, a structure-based approach or a ligand-based approach is used. Structure-based computer aided drug design depends on the information of the target protein structure obtained from X-ray crystallography, NMR or homology modelling to calculate interaction energies for all tested compounds. This approach involves “docking” a process of ligand binding to its receptor or target protein, to identify and optimize drug candidates by examining how the drug interacts with its target and modelling molecular interactions between ligands and target macromolecules.

According to Anson et al (2009) the conventional methods (High Throughput screening) of drug discovery is a lengthy, “expensive, diûcult, and ineûcient process” with low rate of new therapeutic discovery. The average time to develop a new drug has also increased over time (Hurle, Yang et al. 2013). In 2010, it was estimated that the cost of research and development of new molecular entities (NME) was US$1.8 billion (Paul et al 2010). Very few compounds, out of hundreds of thousands tested in animals, reach human clinical trials. This represents an enormous investment in terms of time and money and other resources.

For a very long time, there have been many propositions in improving the efficiency in the drug discovery and development process in the pharmaceutical industry. A Pharma report by PriceWaterhouse coopers in 2005 : “An Industrial Revolution in R&D” stressed the reality that pharmaceutical industry needs to find means of improving efficiency and effectiveness of drug discovery and development in order to sustain itself.”

The report emphasized growth and value of computational approaches to address this issue and projected that it will become dominant approach of drug discovery in the nearest future.

Benefits of computational drug repositioning

There are many benefits presented by computational drug repositioning compared to conventional methods of drug discovery, which involves a trial-and-error approach of lead identification from natural sources or high throughput screening (HTS) of large chemical libraries in vitro.

Firstly, in computational drug repositioning, the pharmacological profile (Pharmacokinetics, safety profile, toxicology and drug interactions) of the drug to be repositioned is well-known (Lu, Agarwal et al. 2012).

Secondly, it is both cost effective and time-efficient as it increases the effectiveness and efficiency of drug discovery at a lower price and decreases the use of animals in the process of lead identification and optimisation (Kapetanovic 2008). The estimated time required for repositioning of a known drug for a new clinical indication can be as low as three years (Hurle, Yang et al. 2013).

References

Anson D, MaJ, HeJ-Q (2009). “Identifying Cardio-toxic Compounds”. Genetic Engineering & Biotechnology News. Tech Note 29 (9) (Mary Ann Liebert). pp. 34– 35. ISSN1935-472X.OCLC77706455.

Hurle, M., L. Yang, et al. (2013). “Computational Drug Repositioning: From Data to Therapeutics.” Clinical Pharmacology & Therapeutics 93(4): 335-341.

Kapetanovic, I. (2008). “Computer-Aided Drug Discovery and Development (Caddd): In Silico-Chemico-Biological Approach.” Chemico-biological interactions 171(2): 165-176.

Paul S, Mytelka D, Dunwiddie C, Persinger C, Munos B, Lindborg R, Schacht A. (2010). “How to improve R&D productivity: the pharmaceutical industry’s grand challenge”. Nature Reviews. Drug Discovery9 (3): 203–14.

Yunusa, A. and Bello, S.O.  (2015) “Computational Drug Design: An Approach In Drug Re-Positioning-A Review” International Journal of Scientific Research Engineering & Technology (IJSRET), ISSN 2278 – 0882   Volume 4, Issue 8.

Wikipedia: Drug discovery. Source: https://en.wikipedia.org/wiki/Drug_discovery?oldid=697280369

Today is World Health Day 2016, and the theme for this year’s commemoration is: “Beat Diabetes”. Diabetes is a chronic, progressive noncommunicable disease (NCD) characterized by elevated levels of blood glucose (blood sugar). It occurs when the pancreas does not produce enough of the insulin hormone, which regulates blood sugar, or when the body cannot effectively use the insulin it produces.

According to a press release from the World Health Organisation (WHO) the number of people living with diabetes has nearly quadrupled since 1980 to 422 million adults, with most living in developing countries, like Nigeria.

WHO is calling all well meaning inhabitants of the world to participate in the battle against diabetes, in order to end the epidemic.

To effectively halt the prevalence of the disease, there are measures needed to expand health-promoting environments to reduce diabetes risk factors, like physical inactivity and unhealthy diets, and strengthening national capacities to help people with diabetes receive the treatment and care they need to manage their conditions.

“If we are to make any headway in halting the rise in diabetes, we need to rethink our daily lives: to eat healthily, be physically active, and avoid excessive weight gain,” says Dr Margaret Chan, WHO Director-General. “Even in the poorest settings, governments must ensure that people are able to make these healthy choices and that health systems are able to diagnose and treat people with diabetes.”

The number of people living with diabetes and its prevalence are growing in all regions of the world. In 2014, 422 million adults (or 8.5% of the population) had diabetes, compared with 108 million (4.7%) in 1980.

Speaking on the prevalence in Nigeria, the Chief Medical Director (CMD) of Lagos University Teaching Hospital (LUTH), Prof. Chris Bode, said though the disease was gradually assuming an epidemic proportion worldwide, as it had become one of the 10 leading causes of death globally, the real situation in Nigeria could not really be established because of lack of data.

He said while the dearth of data continues to affect diabetes management and research, it had continue to ravage many Nigerians because of its silent nature.

Bode said: “Because of our cultural believe that if a condition does not stops one from eating, does not cause pains and bleeding, it is not considered serious,” the disease hides behind many others since it is taken for granted.

The National Association of Resident Doctors of Nigeria (NARD) has said that except the Federal Government expedite action in paying up the backlog of salaries owed its members within 21 days, the nation’s health sector might experience a walkout of its members.

The President of NARD, Muhammad Askira, gave the warning on Monday in Abuja, Nigeria’s capital, lamenting the situation where their members in Osun, Oyo, Imo and Kogi States were owed salaries ranging from three to eight months.

According to Channelstv.com, the group also queried why the situation remained the same despite President Muhammadu Buhari’s pronouncement to care for the welfare of health workers.

The health workers are asking the Federal Government to intervene and find a lasting solution to the issues raised within the 21-day window.

They threatened that if the government failed to attend to their needs, they would embark on a nationwide industrial action by April 25.

The minister of health, Professor Isaac Adewole has said that except there is an immediate increase in the number of available radiotherapy machines in the country, there might be no end in sight to the rising cancer profile in Nigeria.

Adewole who disclosed this during his visit to LUTH, categorically stated that Nigeria needs about 140 radiotherapy machines to address rising cancer cases in the country.

He said only two out of the available seven in the country are functional which are being overstretching for the treatments of 2million cancer patients.

The Minister who urged Nigerians to improve on their lifestyle said 40per cent of cancer cases can be prevented while 40percent are also curable if detected early.

He said late detection of cancer is death even when patients travel abroad for help adding that this why awareness is key to prevent the scourge.

The Minister, who also  ordered free treatments for indigent patients at the hospital, said  until the system put in place an insurance scheme or some form of social health scheme, everyone cannot be taken care of but, only the poor can enjoy such free treatment.

He said “We can also not deny poor Nigerians quality treatment because they have no money. Those who are poor should enjoy our services. We are pleading to Nigerians to be genuine and truthful because we cannot take care of everybody for now, the free treatment is for the poor alone.”

As part of efforts to reduce the health care challenges in the nation, the Federal Government of Nigeria has announced plans to address inadequate facilities in 10,000 primary health care centres across the country.

The Minister of State for Health, Dr. Osagie Ehanire, disclosed the plan in Abuja‎, according to Channels TV reports, stating that  the Federal Government was committed to improving the health care needs of Nigerians in order to sustain the progress so far recorded in the health sector.

Dr Ehanire , who was speaking during a gathering of health experts, as the World Bank convened a round table on the health care sector in Nigeria,  expressed his optimism that  Nigeria is moving in the right direction, having succeeded in reducing the number of child and maternal deaths.

The occasion, which commenced with the inauguration of a policy makers summit, also witnessed the attendance of the acting Country Director of the World Bank, who advised the Federal Government to go beyond rhetoric by addressing the poverty level in Nigeria.

The policy makers summit put together by the World Bank is expected to, among other things, evaluate ‎maternal and child health impact on Nigerians including a general overview of the nation’s health sector.

Worried by the torrent of criticisms trailing the prospects and content of the proposed Unified Scheme of Service (USS) by the leadership of the National Association of Nigerian Nurses and Midwives (NANNM), a group of nurses under the aegis of University Graduates of Nursing Science Association (UGONSA) have decried the situation, demanding clarification from the NANNM president, Comrade Abdulrafiu Alani Adeniji.

The complaint, which was signed by comrade Jude Chiedu, Fwacn, and published on NursingworldNigeria.com, demanded for a certified copy of the USS, in order  to clarify confusing issues therein.

The statement, which reminded the president of his obligation to run an open policy administration, in the interest of all members, cautioned the president on the tendency to turn deaf ears to this call, adding that this could trigger greater protest, if nothing is done to salvage the image of the nursing profession.

“Ignoring them has not helped in any way. Since there has been no rebuttal publication or sensitization by the Leadership of NANNM on these issues raised by UGONSA, your silence has left us at a loss as to making an informed decision on which team we are on”, the publication reads.

In an exclusive chat with pharmanewsonline.com, the NANNM president, Comrade Adeniji  gave reasons for the actions of NANNM, acknowledging that  the USS actually originated from them,  and its not strange to anybody, except those who are out to create confusion in the profession.

He said:”There is justification for the USS, because just like there is entry point into any profession, the USS stated clearly the criteria to practice nursing in Nigeria, and this has not been hidden to any nurse. The USS also states that obtaining a degree in nursing does not automatically qualify anyone one for practice, until he/she sits for qualifying examination to practice”.

Describing the protest of UGONSA’s members as a foul cry, where there is no cause for alarm, he explained that once a document is filed through the public service rule, it is regarded as classified document, which remains confidential, until its approval. Thus, circulating such document is not feasible for now.

“The issue with UGONSA’s members is the mere fact that they are looking for recognition, because how many practicing nurses are graduates presently. They are yet to be members of NANNM, and thus have to right to demand for the USS”, he insisted.

Adeniji further condemned the action of UGONSA’s members, stating that having gone ahead to register with the Corporate Affairs commission (CAC) does not empower them to protest over issues in the profession.

As Nigeria joins the rest of the world to mark the 2016 World Tuberculosis Day today, the World Health organisation (WHO) is calling on countries and partners to “Unite to End Tuberculosis” by the year 2030.

The theme of the 2016 World TB Day commemoration in Nigeria is ‘’Find TB, Treat TB and Working together to Eliminate TB’’ while the global slogan is “Unite to End TB.”

The WHO made the call earlier in a press release, saying ending TB is imperative, as we enter the era of the Sustainable Development Goals (SDGs). Ending tuberculosis (TB) by 2030 is a target of the SDGs and the goal of the WHO End TB Strategy.

The press release reads in part:

That is an ambitious aim. While there has been significant progress in the fight against TB, with 43 million lives saved since 2000, the battle is only half-won: over 4 000 people lose their lives each day to this leading infectious disease. Many of the communities that are most burdened by tuberculosis are those that are poor, vulnerable and marginalized.

Greater collaboration needed

Ending TB will only be achieved with greater collaboration within and across governments, and with partners from civil society, communities, researchers, the private sector and development agencies. This means taking a whole-of-society and multidisciplinary approach, in the context of universal health coverage.

Momentum is growing at country and community levels – including in the 30 countries with the highest TB burden (over 85% of the global burden). A number of countries are strengthening the strategic agendas of their TB programmes, by adopting newer tools, extending access to care and linking with other parts of government to reduce the financial costs borne by patients. Other countries are partnering with researchers to speed development of diagnostic tests, drugs and vaccines, and to improve delivery.

Country progress on TB

For example, India which is home to more people ill with TB and multidrug-resistant TB (MDR-TB) than any other country, has committed to achieving universal access to TB care with its campaign for a TB-Free India. The Ministry of Health and Family Welfare is expanding its capacity to test patients rapidly for drug-resistant TB and is initiating use of bedaquiline, a new, WHO-recommended drug in MDR-TB treatment. In addition, by making TB case notification mandatory in 2012 and by intensifying efforts to engage the private sector, case notifications rose 29% in 2014 alone.

In working towards universal health coverage, South Africa has greatly expanded access to Xpert MTB/RIF, a WHO-recommended rapid molecular test for TB and drug-resistant TB. South Africa has the largest number of people living with HIV who are receiving TB preventive treatment in the world.

In Thailand, where a large percentage of the population has access to health services at modest cost, efforts are focusing on ensuring that all residents – including migrants – have access to TB treatment.

In the Russian Federation, a high-level working group across government institutions has strengthened TB policies over the last 15 years. Since 2005, Russia reports that TB mortality rate has dropped more than 50%, and TB notifications have dropped 20%. WHO will work with the Ministry of Health in 2016 to assess these data and help assess the factors leading to such a decline.

Brazil and Viet Nam, both with effective basic TB services, are investing in research efforts to drive down the TB burden. Brazil has formed a national network of TB researchers, REDE-TB, which is working on basic science, clinical trials, and operational research priorities. Viet Nam has formed VICTORY (“Viet Nam Integrated Centre for Tuberculosis and Respirology Research”), a research partnership that is initiating a TB prevalence survey and developing tools to prioritize interventions for MDR-TB.

Challenges remain

Despite these advances, formidable challenges remain including fragile health systems, human resource and financial constraints, and the serious co-epidemics with HIV, diabetes, and tobacco use.

MDR-TB is another critical challenge. Urgent and effective action to address antimicrobial resistance is key to ending TB by 2030. So are increased investments, as the global tuberculosis response remains underfunded for both implementation and research.

WHO is committed to continuing its work with countries and partners around the world to address these challenges and to accelerate collective action to end the TB epidemic altogether.

Key TB Facts

TB ranks alongside HIV/AIDS the world’s top infectious disease killer.

In 2014, 9.6 million people fell ill with TB and 1.5 million died from the disease, including 380 000 among people living with HIV.

More than 95% of TB deaths occur in low- and middle-income countries, and TB is among the top 5 causes of death for women aged 15 to 44.

In 2014, an estimated 1 million children became ill with TB and 140 000 children died.

TB is a leading killer of HIV-positive people: in 2014, 1 in 3 HIV deaths was due to TB.

Globally, in 2014, an estimated 480 000 people developed MDR-TB.

The TB death rate dropped by 47% between 1990 and 2015.

An estimated 43 million lives were saved through TB diagnosis and treatment between 2000 and 2014.

The WHO End TB Strategy aims to reduce TB deaths by 90% and to cut new cases by 80% between 2015 and 2030, and to ensure that no TB-affected family faces catastrophic costs due to TB.

Since the inauguration of World Water Day in March 22, 1993 by the United Nations General Assembly, the day had been set aside to create awareness on the need for safe water consumption and provision.

The theme for this year’s celebration: “Water and Jobs”, made it clear that availability of portable water is paramount in creating conducive work environments and homes. It is however regrettable that most homes in Nigeria, still lack means of hygienic water, talk less of workplaces.

In the light of this commemoration, the Nigerian government needs to rise to its obligation of providing safer water for its citizens, as improving these rights, and improving access to safer water, we can improve the lives of everyone.

Then comes the question, why do you need to drink water?

It is generally said that water is life, this explains the reason every cells and organs in the body need water to function effectively. Water is also an indispensable lubricant in the human system that lubricates the joints, protect the spinal cord and other sensitive tissues, regulate body temperature and assist the passage of food through the intestines.

How much water is ideal to drink?

The recommended amount of water that should be drunk per day varies from person to person depending on factors such as how active they are and how much they sweat. There is no universally agreed upon threshold of water consumption that must be reached, but there is a general level of consensus as to what a healthy amount is.

According to the Institute of Medicine (IOM), an adequate intake for men is approximately 13 cups (3 litres) a day. For women, an adequate intake is around 9 cups (2.2 litres).

Many people may have heard the phrase, “Drink eight 8-ounce glasses of water a day,” which works out at around 1.9 litres and is close to the IOM’s recommendation for women. Drinking “8 by 8” is an easy-to-remember amount that can put people on the right track in terms of water consumption.

Water also helps dissolve minerals and nutrients so that they are more accessible to the body, as well as helping transport waste products out of the body. It is these two functions that make water so vital to the kidneys.

Just like a nightmare, Lassa fever has taken over from where Ebola stopped in West Africa, especially in Nigeria which, according to the World Health Organisation (WHO), reportedly recorded 159 suspected cases of Lassa fever, including 82 deaths, across 19 states between August 2015 and January 2016.

For most West African countries, especially Nigeria, that had devastating experiences with the Ebola outbreak, it isn’t yet time to heave a sigh of relief as the sub-region battles the onslaught of Lassa fever. The last Ebola outbreak, which was the worst of its kind, tormented the West African countries between December 2013 and November 2015, and infected about 29,000 people, claiming over 11,315 lives.

Like the Ebola virus, the Lassa virus is transmitted through close contact with the virus host or the sweat, vomit, blood or other bodily fluids of an infected person, or the recently deceased. Both cause severe fever and muscle pain, weakness, vomiting and diarrhoea. In many cases, they shut down organs and cause unstoppable internal bleeding. Patients often succumb within 3 to 21 days.

However, unlike Ebola, Lassa is treatable with Ribavirin – an antiviral drug that is only effective if administered within the first six days after the disease onset.  Also, Lassa fever patients benefit from careful monitoring of fluid, electrolyte and oxygen levels.

Infection with Lassa virus often arises from exposure to infected rodents. Person-to-person transmission occurs through direct contact with sick patients in both community and health care settings. Those at greatest risk are persons living in rural areas where the carriers are found. Health care workers are also at risk if adequate infection control practices are not maintained.

According to the Wikipedia, Lassa fever or Lassa haemorrhagic fever (LHF) is an acute viral haemorrhagic fever caused by the Lassa virus and first described in 1969 in the town of Lassa, in Borno State, Nigeria. Lassa fever is a member of the Arenaviridae virus family. Similar to ebola, clinical cases of the disease had been known for over a decade, but had not been connected with a viral pathogen.

Lassa virus frequently infects people in West Africa. It results in 300,000 to 500,000 cases annually and causes about 5,000 deaths each year. Outbreaks of the disease have been observed in Nigeria, Liberia, Sierra Leone, Guinea, and the Central African Republic. The primary animal host of the Lassa virus is the Natal multimammate mouse (Mastomys natalensis), an animal found in most of sub-Saharan Africa. The virus is probably transmitted by contact with the faeces or urine of animals accessing grain stores in residences.

Given its high rate of incidence, Lassa fever is a major problem in affected countries because in 80 per cent of cases, the disease is asymptomatic, but in the remaining 20 per cent, it takes a complicated course. The virus is estimated to be responsible for about 5,000 deaths annually and it accounts for up to one-third of deaths in hospitals within the affected regions and 10 to 16 per cent of total cases.

The Wiki report states further that after an incubation period of six to 21 days, an acute illness with multiorgan involvement will develop. s nonspecific symptoms include fever, facial swelling, and muscle fatigue, as well as conjunctivitis and mucosal bleeding.

An acute viral illness, Lassa fever, according to the Federal Ministry of Health, has so far claimed over 70 lives across over 17 states of the country and the FCT.

In order to curtail the spread of the disease, the federal government has created the Lassa Fever Rapid Response Committee, which goal is to control and prevent the spread of the malady. Public health officials have also asked Nigerians to stop burning bushes as this drives rats out of the bush and into nearby houses. Government has also placed a ban on consumption of rats that are a delicacy common to some states in the Middle Belt region of the country, so as to curtail the spread of the disease.

The garri connection

The Medical and Health Workers Union, Lagos State Council, has discouraged the consumption of soaked garri as a preventive measure against Lassa fever. Chairman of the Union, Mr Razak Adeofalade, was quoted to have said: “We are going to encourage members of the public to depart from the process of drinking garri. At this period, it is better that the cassava flour is utilised for eba, because of the use of hot water. We are waging total war and that is: ‘War against Rats,’ and that is what we are going to do to ensure we do not have more victim of Lassa fever in the state.”

Continuing, he said: “Garri is often fried half-dry and subsequently dried on polythene sheets on tarred roads or compounds in villages, where rats feed on them, and in the process defecate and urinate on the garri, which dries up with it. If used for eba, the virus may die because of the hot water used. But if soaked in normal water and consumed, the virus is directly ushered in.”

However, in a swift reaction, the association of cassava processors, through their chairman, Pastor Tayo Adewumi, reportedly debunked the warning on garri, stressing that the virus can hardly survive the production process. He explained that the cyanide content in cassava makes it difficult for rats to feed on it during production process.

He however drew attention to the need for better hygienic practices at home, saying that if not properly stored after production, rats could feed, urinate and defecate on it and by so doing people could come down with Lassa fever.

Remedial measures

At a meeting of the National Council of Health in Abuja to adopt strategies for combating Lassa fever and other viral diseases in the country, the minister of health, Prof. Isaac Adewole, warned health managers not to deceive executives by keeping silence on the spread of the disease.

During the emergency meeting, Adewole was quoted as saying, “We currently have testing capability in 14 testing centres, some of which are in Maiduguri, Kano, Iddo, Irrua, Lagos, Port Harcourt and the FCT. We have treatment centres all over the country. We have enough personnel for managing Lassa fever. Unlike Ebola Virus Disease that is untreatable, Lassa fever is treatable. But we must start treatment on time to enable us to save the patients.”

The minister while assuring the public that the federal government would maintain high level of alert to eliminate the disease soon, added that the ministry had deployed rapid response teams to all affected states to assist in investigating and verifying fresh cases of the disease.

He further added that government had raised a four-man expert committee, led by Prof. Michael Asuzu, to visit Kano, Niger and Bauchi States, saying the committee would embark on a fact finding mission, assess the current situation, document response experiences, identify gaps and proffer recommendations on how to prevent future occurrences.

According to him, the task of the committee was to document lessons learnt for better planning of an affective responsive. He also said the federal government had also given the Committee on the Eradication of Lassa fever in Nigeria, headed by Prof. Oyewale Tomori, president of the Nigeria Academy of Science, a mandate to provide a one-health approach to the complete elimination of the disease in the country.

Issues for consideration

However, beyond the promises by the state and federal governments, there are fundamental issues that need to be addressed, if the country must conquer the scourge of Lassa fever. A nation as diverse as Nigeria should have a national response strategy for disease outbreak which should be automatically activated once there is an outbreak of a highly infectious disease like Lassa fever. It is imperative to strengthen the nation’s National Centre for Disease Control to ensure this important agency is able to deliver on its mandate of helping to prevent disease outbreaks and needless deaths of Nigerians from conditions like Lassa fever that are preventable and treatable.

Lassa fever has been with us since 1969; therefore, we must come out of the box and design a new and sincere approach to dealing with a disease that is quite endemic in our region, rather than continue with the fire brigade methods of raising alarm, waiting for ministerial updates on deaths tolls on television, setting up committee, and begging for international donations.

It is also important that Nigerians themselves are orientated to pay more attention to disease prevention. The health ministry must leave no stone unturned in ensuring that Nigerians are enlightened about strategies to adopt to prevent diseases because prevention is better than cure.

Importantly, elimination of rats is key to controlling the Lassa fever virus. Also, proper sanitization of the environment is advisable, while people should make sure that their house is not conducive for rodents by getting rid of old newspapers and books that can be food to them. Beyond this, they should store their food items in containers to avoid being contaminated by rodents. Also, they should endeavour to wash every plate before using them and immediately after usage, and they should dispose of all dirt in air-tight plastic containers that cannot be accessible to rats.

A ‘nutraceutical’ is any nontoxic food-derived supplement that has scientifically-proven health benefits for both the treatment and prevention of disease. This term was coined in 1989 by Stephen DeFelice. Nutraceuticals may range from isolated nutrients, dietary supplements to genetically engineered food, herbal products, and processed products such as cereals, and beverages.

The growing interest in nutraceuticals reflects the awareness of consumers about epidemiological studies indicating that a specific diet or component of the diet is associated with a lower risk for a certain disease. A typical example is seen in the French paradox which drew the attention of researchers, in which low incidence of cadiovascular disease was observed in the french population associated with red wine consumption, but having a greater amount of saturated fat in their average diet than in other countries.

In recent years, proteins and peptides have gained prominence as potential source of nutraceuticals. Many studies have shown that peptides from various food sources possess bioactivities, including antihypertensive, antioxidant, anticancer, antimicrobial, and opioid activities as well as immuno-modulatory and cholesterol-lowering properties, suggesting their potential use as nutraceuticals for health promotion and disease risk reduction.

Peptides are short polymers of amino acids linked together by peptide bonds. One or more polypeptide subunits makeup a protein molecule. Proteins are essential components of tissues in living organisms and participate in a large number of physiological processes within cells. In foods, proteins are an important macronutrient, serving as a source of energy and amino acids, which are essential for normal growth and maintenance of the body functions. The physiological and functional properties of food proteins are attributed to peptides with biological activities, released from their precursor proteins during gastrointestinal digestion or food processing.

Such peptides with biological activities are referred to as bioactive peptides. Bioactive peptides are specific protein fragments with hormone or drug like activity that eventually modulate physiological function through binding interactions to specific receptors on target cells leading to induction of physiological responses. The activity of these peptides is dependent on their amino acid composition and sequence. Moreover, some peptides are multifunctional and can exert more than one effect mentioned. Most of the dietary peptides having biological activity which have been investigated to date originated from milk. Examples include immunoglobulins, caseins, whey proteins etc. However, proteins from other animal sources, as well as plant proteins, have been reported to exert specific bioactivities.

The first biologically active peptide found in milk was opioid peptides followed by the immunomodulatory peptides.

 Anticancer activity

Bioactive proteins and peptides have been associated in preventing the development of different types of cancer. Soybean Kunitz trypsin inhibitor, was reported by Kobayashi et al in 2004 to suppress ovarian cancer cell invasion by blocking urokinase activity. Bowman Birk protease inhibitor (BBI), a water-soluble protein isolated from legumes and many monocotyledonous seeds, has shown anticarcinogenic activity in in vitro and in vivo studies and is now intensively studied as a cancer chemopreventive agent in clinical trials. Lunasin, a 43 amino acid peptide is a novel chemopreventive agent from soybean, and has been found to suppress chemical carcinogen and viral oncogene-induced transformation of mammalian cells and inhibit skin carcinogens in mice.

 Cholesterol-lowering effect

Many proteins and their peptides are known to exert a cholesterol-lowering effect, among which soybean is the most well-recognised source of hypocholesterolemic proteins and peptides and soybean-rich diet has become the most potent dietary tool for treating hypercholesterolemia. An early study by Sirtori et al. in 1977 have reported that 7S globulin, a major storage protein in soybean, decreased plasma cholesterol concentration by 35 per cent in rats. Recent studies have shown that soy protein reduces circulation of triacylglycerols and cholesterol in hypercholesterol individuals. Proteins from soybean given to animals or human subjects by oral administration are subjected to protease digestion in the gastrointestinal tract, releasing the bioactive peptides which inhibit cholesterol absorption.

 Antihypertensive activity

Antihypertensive peptides have been found effective in treating and preventing hypertension primarily by inhibiting the angiotensin-converting enzyme (ACE), which is mainly responsible for  the regulation of blood pressure and maintenance of the equilibrium of water and salts in the body (electrolyte homeostasis). ACE is also responsible for the inactivation of the vasodilator bradykinin, which in turn leads to increase in blood pressure. ACE acts by converting the peptide angiotensin I with 10 amino acid residue into angiotensin II with 8 amino acid residue. Angiotensin II is a potent vasoconstrictor which also has a regulatory effect on cellular lipoxygenases and catalyses the oxidation of low-density lipoprotein (LDL), a process implicated in atherogenesis. Antihypertensive peptides can decrease the activity of ACE and indirectly reduce the level of angiotensin II, thereby exerting a vasorelaxing effect on blood vessels. Examples of Antihypertensive peptides include Lactoglobulin, Lactalbumin, αs1-Casein and β-casein which are derived from milk and Ovalbumin derived from egg.

 Antimicrobial activity

A broad spectrum of antimicrobial peptide protects the gastrointestinal tract against pathogenic bacteria and viruses. A typical example of peptide with antimicrobial activity is Lactoferricin, formed from Lactoferrin an iron-binding glycoprotein during digestion. lactoferrin is responsible for inhibition of growth of pathogens by iron scavenging.

Antimicrobial peptides are also of immense importance for their potential application in food preservation and for therapeutic use in health care. Bioactive peptides have been identified in a wide variety of natural sources from microorganisms to animals and plants. Antimicrobial peptides display inhibitory effects against microbe-caused food deterioration. Advantages of antimicrobial peptides over chemical preservatives include better selectivity and sensitivity on target microorganisms, fewer adverse effects introduced to the food, lower intensity of heat treatment required, and retaining of organoleptic and nutritional properties of food, such as less acidic and lower salt content.

 Immunomodulatory properties

Immunomodulating peptides have been detected in human as well as in cow milk proteins. From human milk protein digests, two peptides, β-casein and α-lactalbumin enhance the phagocytic activity of macrophages both in mice and humans and enhance resistance against certain bacteria in mice. Immunomodulating peptides have also been found to stimulate the proliferation of human lymphocytes, the phagocytic activities of macrophages and antibody synthesis. The peptides may stimulate the proliferation and maturation of T cells and natural killer cells for defence of  infants against a large number of bacteria, particularly enteric bacteria.

References

Kobayashi H., Suzuki M., Kanayama N., & Terao T. (2004) Clin. Exp. Metastasis 21, 159–166

FitzGerald R. and Murray B. (2006). Bioactive peptides and lactic fermentations. International Journal of Dairy Technology, 59, 118-125.

Shrikant S., Raghvendar S, Shashank R. (2011). Bioactive Peptides: A Review. Int. J. Bioautomation, 15(4), 223-250.

Shahidi F. & Zhong Y. (2008). Bioactive Peptides. Journal of AOAC International vol. 91, no. 4

Sirtori, C.R., Agradi, E., Mantero, O., Conti, F., & Gatti, E. (1977) Lancet 1, 275–277

Tapas A, Sakarkar D and Kakde R (2008). Flavonoids as Nutraceuticals: A Review. Tropical Journal of Pharmaceutical Research, 7 (3): 1089-1099

Walther B, Sieber R. (2011). Bioactive proteins and peptides in foods. International Journal for Vitamin and Nutrition Research 81(2-3):181-92. DOI: 10.1024/0300-9831/a000054

The recent dinner reception organised in honour of the newly inaugurated Fellows of the Lagos State branch of the Pharmaceutical Society of Nigeria (PSN) became a rallying point for improved service to the society, as the new Fellows were urged to stop at nothing but all-round excellence.

The colourful occasion, which was also used to honour the immediate past president of the PSN, Pharm. Olumide Akintayo; Commissioner for Youth and Social Development, Pharm. Uzamat Akinbile-Yusuf; and Commissioner III, Lagos State Health Service Commission, Pharm. (Otunba) Seun Osikoya, was held at the Sheraton Hotel and Towers, Ikeja, Lagos.

Present at the dinner were the current PSN President, Pharm. Ahmed I. Yakasai; PCN Registrar, Pharm. N.A.E Mohammed; Pharm. Jimi Agbaje; Pharm. Ade Popoola, and other personages in the Nigerian pharmaceutical industry.

Addressing the Fellows on a pep talk titled: “Excellence beyond fellowship”, Pharm. Popoola urged them to keep the honour bestowed on them by the PSN, by living up to the expectations of the Society, adding that fellowship is the beginning of service.

Noting that fellowship is an honour with attendant responsibility and accountability, Popoola discouraged the Fellows from toeing the lines of some others who reneged on their responsibilities, as soon as they were decorated with the fellowship of PSN.

The former PSN Board of Fellows chairman charged the Fellows to strive for distinction in professional ethics, practice and morality, stressing that engaging in unethical conduct is a direct assault on the profession.

“In any area of practice you are, distinguish yourself, and uphold the pharmacy slogan –‘as men of honour, we join hands’, more than ever before. Try as much as possible to distance yourself from the practice of R&G, which never promotes the tenets of the profession”, he charged.

Earlier on, chairman of the occasion, Pharm. Agbaje, had asked the new Fellows a rhetorical question: “After PSN fellowship, what next – is it just the title or the need to impact the society”? The question which was meant to spur the Fellows seemed to generate the expected impact, as the Fellows listened to him with rapt attention.

Agbaje commended the personality and courage of the PSN president, disclosing that he had for long known Pharm. Yakasai to be an active member of the PSN who  is well grounded in all matters of the profession.

Appreciating all the guests in attendance, Pharm. Gbenga  Olubowale, who was the host and also one of the new Fellows, said the gathering was to celebrate excellence, as most of the Fellows had distinguished themselves in their respective areas of service.

Describing Pharm. Akintayo, as a successful leader, who handed over the baton of leadership smoothly, Olubowale said posterity would always remember his good works and PSN Lagos would always give him their support.

He also expressed gratitude to the two Lagos commissioners in attendance, pledging the unalloyed allegiance of the PSN branch to them.

Olubowale further charged all the newly decorated Fellows to become part of the solution to the myriads of challenges of facing the country.

Responding to all the accolades showered on him, Akintayo said he felt fulfilled for bequeathing a well-grounded and dependable president, as well as a wonderful crop of Fellows to the society.

“It is a night of gratitude,” he said. “I am happy to be back home, and there is no gainsaying that the PSN leads and others follow. The immensity of the support of Lagos PSN has contributed greatly to my success.”

He urged the new president to always look inward into the profession and to harness the potentials of the practitioners for the maximum benefit of the society.

In this exclusive chat with Temitope Obayendo, Dr Olugbenga Awobusuyi, a consultant nephrologist of high repute with the Lagos state Teaching Hospital (LASUTH) and an associate professor at the Lagos State University College of Medicine (LASUCOM), opens up on the prevalence of Chronic Kidney Disease (CKD) in Nigeria, implicating uncontrolled diabetes and hypertension as the major culprits. Excerpts:
Chronic Kidney Disease (CKD), also known as kidney failure, has become more rampant these days, what could be responsible for this?
The reason for the prevalence of CKD is the surge in conditions that predispose people to renal failure, which are hypertension and diabetes. Nowadays many people are coming down with uncontrolled hypertension and diabetes, thus the prevalence of CKD in our society.
There is the World Kidney Day celebration to create awareness on the disease, but there are further campaigns done by stakeholders in the hospitals during our routine clinic visits, to enlighten patients who might be at risk to come for check-ups.
Our kidneys are endowed with functional reserves, which could prevent a patient from having any symptoms years after the disease might have set in, in fact, this could delay symptoms until after 60 -70 percent of the kidney functions might have been damaged.

Before now, kidney failure used to be associated with the elderly, but it is becoming also common among the younger generation. What predisposes a youth to kidney failure?
Just as hypertension is very common, so is what is called glumerulonephritis also common. Glumerulonephritis is a situation where a patient’s body produces some substances like protein, called antibodies, which attack the kidney to destroy it. Although this condition is not common in our environment, it is a cause of renal failure. We have a lot of diabetics, habitual consumers of native medications, and the analgesics addicts, who are already down with the disease. Some infections like HIV, Hepatitis B, Sickle Cell, patients with cysts in the kidney, prostate enlargement, kidney stones, can also cause CKD. Glumerulonepheritis could be responsible for the disease in young people.

During the celebration of the 2013 World Kidney Day (WKD), President of the Nephrology Association of Nigeria (NAN), Dr Ebun Bamgboye, said 36.8 million Nigerians are suffering from kidney disease at different stages. Two years after, what do you think the statistics will look like now?

We don’t have any hard statistics on the prevalence, although the Nephrology Association of Nigeria (NAN) is taking some steps to have a renal register, though it’s still at the infant stage. Nonetheless, there are a number of studies conducted in some communities, which indicated that the prevalence is still between 17 and 21 per cent of the population.

Can you explain the stages of kidney disease, the symptoms, and at what point patients should seek medical advice?

It actually has five stages, based on what we call Glumerulo Filtrating Rate (GFR), which reflects the overall functions of the kidney. The first stage is 90 or more millimetre per minute; stage two is GFR 60-89; stage three, GFR 30-59; Stage four, GFR 15 -29 and stage five is lower than 15 GFR.
It is at stage five we do dialysis for a patient. What we generally do is to treat the underlying disease. We also consider factors that make kidney functions decline drastically, some of which are uncontrolled diabetes and hypertension. However, when the condition becomes uncontrolled, we do kidney transplant, which is very expensive.

Is it possible to treat the disease if detected earlier?
It is one of the messages we are trying to pass across to the populace – that chronic kidney disease is preventable, and many of the causes are treatable. If patients are diagnosed early enough, their diabetes and hypertension can be well managed to prevent renal failure. This could be done by slowing down the deterioration rate of the kidney, thereby ensuring adequate management of the underlying conditions. Patients must always ensure they meet their doctors at the right time, as well as take their medications as prescribed. If this is done, there are chances that the rate of death associated with kidney failure will be reduced.
For everybody to understand the symptoms of the disease, there is need to know the functions of the kidney. The kidney actually excretes water and other waste products from the body; secondly it regulates the internal environment, by making the system conducive for the internal organs e.g., the electrolytes; and thirdly, it regulates blood pressure. It is also responsible for the production of a very active form of Vitamin D, which makes our bones strong. It produces another substance called erytopoietin which stimulates our bones to be stronger.
Thus, once a kidney start failing in carrying out these functions, then it’s a symptom of an ailment. For instance, when a patient cannot eliminate the water he/she takes in, through sweat and urine, when he finds it difficult to pass out excreta, then there will be an accumulation of waste products in the body, which is an indication of kidney failure.
What we usually tell people during awareness campaign is that they should always check their urine; once it’s foamy, it’s an indication of protein in the urine, which is a symptom of CKD. Diabetics need to be more conscious about their health, because it’s a condition that has more tendencies to damage the kidney. Once these symptoms are detected, patients need to visit the hospital for screening. It’s also worthy of note, that the initial medical tests are not expensive. Urine test costs around N500, while blood screening is around N1000.

How many forms of kidney failure exist?
There are two forms of kidney failure, acute and chronic. Acute kidney failure could occur within an hour or two, due to severe infections, loss of blood through childbirth, severe diarrhoea and cholera – but the system normalises itself few hours later. Diarrhoea and cholera patients could be predisposed to this condition. At times, they lose consciousness and may even convulse. However chronic kidney disease is our focus of discussion.

With your involvement in medical practice so far, can you estimate the cost of a successful kidney transplant?
A kidney transplant goes for about N5 million to N6 million. All over the world, I’m not sure many patients can afford that. However, in most cases where they can access the facility, the government usually pays for the chunk of the fee.

How many nephrology experts do we have in the country?
The ratio of nephrologists in Nigeria to patients is about 150,000 to about 40 million patients.

Can it be said that people without diabetes or hypertension are not at risk of CKD?
Yes, they are not at risk, but if they have a family history of CKD, diabetes or hypertension, they should be going for check at least once a year. Especially if they are above 40 years, regular check up is important.

Considering the state of our health care facilities, is there any hope for Nigeria in overcoming CKD?
It depends on the will of the government of the day. If there is political will in the provision of local facilities, building of good facilities, provision of manpower, and monitoring of the administrative section for effectiveness, then cases of CKD would be drastically reduced.

What is your advice to Nigerians as regards kidney diseases and their general health conditions?
They should always participate in medical screening exercises. Hypertensives and diabetics should keep their appointments with their health care givers and also ensure they meet qualified doctors, not roadside quacks.

Good news to all pharmacists, as the International Pharmaceutical Federation (FIP) announces the 6^th World Pharmacists Day, to hold on September 25, 2016 across the globe.

The theme for this year’s event: “Pharmacists: Caring for you”, was chosen to reflect the important role of pharmacists in providing care to the public, and also to highlight the emotional connection they have with their patients.

According to a press statement released by FIP, signed by the President, Dr Carmen Peña, the role of pharmacists has evolved from that of a provider of medicines to that of a provider of care. Pharmacists have a vital role in the outcome of pharmacological therapies and ultimately strive to improve patients’ quality of life.

The press release reads in part:

“World Pharmacists Day, now in its sixth year, is used by FIP’s members around the globe to highlight the impact and added value of the pharmacy profession and its role in improving health to authorities, other professions and the media, as well as to the general public.

“FIP has produced a number of resources in the six official United Nations languages which pharmacists and professional associations can use in support of World Pharmacists Day. These include a new look logo, official campaign images that feature real pharmacists, and materials for social media.

“FIP is inviting individual pharmacists to support World Pharmacists Day by creating profile pictures for social media using an official FIP Twibbon or a specially designed “I care for you” placard, which can be printed and held in photographs. The resources are available now at www.fip.org/worldpharmacistsday.

“Pharmacists have the expertise to provide patient care services that are cost-effective and of high quality. They are the most accessible health professionals, and the public places great trust in them, as shown by many surveys ranking pharmacists among the most trusted professions. We encourage all pharmacists to make use of World Pharmacists Day; a wonderful opportunity to promote our profession,” said Mr Luc Besançon, FIP CEO and general secretary.

As a way of cementing mutual relationship in the industry, the PSN President, Pharm. Ahmed Yakasai, accompanied by his executive members,  recently paid a courtesy visit to Pfizer Specialties Ltd.Picture below was captured during the visit.

Drug discovery is the process by which new medications are discovered. Historically, drugs were discovered after screening by identifying the active ingredient from herbal remedies or crude extracts from plants or microorganisms suspected to have potential biological activity without the knowledge of their biological target. Only after the active principle has been identified was an effort made to identify the biological target. This approach to drug discovery is known as classical pharmacology.

It is understood that individual chemicals are required for the biological activ­ity of a drug. This is based on the premise that drugs mediate their effect in the human body by specific interactions of the drug molecule with its target – biological macromolecules, such as proteins or nucleic acids in most cases. A drug target is the naturally existing cellular or molecular structure involved in the physiological/pathological pathway of interest that the drug-in-development is meant to act on.

Modern approach to drug discovery is based on the understanding of the aforementioned principle of drug action, employing the use of High Throughput Screening (HTS) of large chemical libraries of synthetic small molecules, natural products or extracts against isolated biological targets to identify a compound that is capable of eliciting the desirable therapeutic effect in a process known as reverse pharmacology. The method is the most fre­quently used approach today and has the advantage of requiring minimal compound design or prior knowledge. Although traditional HTS often results in multiple hit compounds, some of which are capable of being modified into a lead and later a novel therapeutic, the hit rate for HTS is often extremely low.

It is generally recognised that this approach to drug discovery and development (the use of HTS) is a time and resource consuming process. As noted by Anson et al (2009) despite advances in technology and understanding of biological systems, current approach to drug discovery is still a lengthy “expensive, difficult, and inefficient process” with low rate of new therapeutic discovery. Estimates of time and cost of currently bringing a new drug to market vary, but 7–12 years and $ 1.2 billion are often cited. In 2010, it was estimated that the cost of research and development of new molecular entities (NME) was US$1.8 billion. Thus, it is evident that pharmaceutical industry needs to find means of improving efficiency and effectiveness of drug discovery and development in order to sustain itself.

New approach

An emerging approach to drug discovery, involving the use of computing power to streamline drug discovery and development process, is rapidly gaining popularity and shows some promise in reducing time and cost in drug discovery process. Various terms are being applied to describe this approach, including Computer-Aided Drug Design (CADD), Computational Drug Design, Computer-Aided Molecular Design (CAMD), Computer-Aided Molecular Modelling (CAMM), Rational Drug Design, In Silico Drug Design, and Computer-Aided Rational Drug Design.

This approach leverages on chemical and biological information about ligands and/or biological targets to identify and optimise new drugs. This has been made possible by increase identification of molecular targets, elucidation of the 3D structures by X- ray crystallography and nuclear magnetic resonance (NMR), availability of commercial, private or public data bases (of biological targets and ligands) and availability of computer-aided drug design softwares.

CADD employs the use of in silico filters to identify hits (active drug candidates), eliminate compounds with undesirable properties (poor activity and/or poor Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET), selects the most promising candidates for further evaluation, and optimises these leads i.e. transform biologically active compounds into suitable drugs by improving their physicochemical, pharmaceutical, ADMET/PK (pharmacokinetic) properties.

A successful CADD campaign will allow identification of multiple lead compounds. Lead identification is often followed by several cycles of lead optimisation and subsequent lead identification, using CADD. Lead compounds are tested in vivo to identify drug candidates.

 How it works

The process of drug discovery, using CADD approach begins with the identification of a therapeutic target against which a drug has to be developed. Depending on the availability of structural information, a structure-based approach or a ligand-based approach is used. Structure-based computer aided drug design depends on the information of the target protein structure obtained from X-ray crystallography, NMR or homology modelling to calculate interaction energies for all tested compounds. This approach involves “docking” a process of ligand binding to its receptor or target protein, to identify and optimise drug candidates by examining and modelling molecular interactions between ligands and target macromolecules.

Ligand-based computer-aided drug design approach, on the other hand, is used when 3D structural information of the target is not available and involves the analysis of compounds known to interact with a target of interest. This method relies on the Similar Property Principle, published by Maggiora and Shanmugasundaram (2011). It states that molecules that are structurally similar are likely to have similar properties. Structural properties considered in this approach include molecular weight, surface areas, ring content, atom types, electro-negativities, atom distribution, interatomic distances, bond distances, planar and non-planar systems, rotatable bonds, symmetry,   functional group composition, aromaticity, solvation properties, and many others.

The overall goal is to characterise compounds in such a way that the physicochemical properties most needed for their desired interactions are retained, whereas unnecessary information not relevant to the interactions is discarded. It is considered an indirect approach to drug discovery in that it does not necessitate knowledge of the structure of the target of interest.

Advantages

According to Kapetanovic (2008) computational drug design expedites and facilitates the process of drug discovery from target identification, hit identification, hit to lead selection and lead optimisation. It increases the effectiveness and efficiency of drug discovery at a lower price, compared to the conventional drug discovery and decreases the use of animals in the process of lead identification and optimization.

Another benefit of in CADD is application in the screening of virtual compound libraries, also known as virtual High Throughput Screening (vHTS). This allows researchers to focus resources on testing compounds likely to have the activity of interest. In this way, a researcher can identify an equal number of hits while screening significantly less compounds, because compounds predicted to be inactive with high confidence may be skipped.

Avoiding a large population of inactive compounds saves money, time and resources, just as the pharma mantra goes, “fail fast, fail early”.

References

• Anson D, Ma J, He J-Q (May 2009). “Identifying Cardiotoxic Compounds”. Genetic Engineering & Biotechnology News. TechNote 29 (9) (Mary Ann Liebert). pp. 34–35. ISSN 1935-472X. OCLC 77706455. Archived from the original on 25 July 2009. Retrieved 25 July 2009
• Kapetanovic I.M. (2008) Computer-Aided Drug Discovery and Development (CADDD): In Silico-Chemico-Biological Approach. Chem Biol Interact. 2008 January 30; 171(2): 165–176. doi:10.1016/j.cbi.2006.12.006.
•  Paul SM, Mytelka DS, Dunwiddie CT, Persinger CC, Munos BH, Lindborg SR, Schacht AL (Mar 2010). “How to improve R&D productivity: the pharmaceutical industry’s grand challenge”. Nature Reviews. Drug Discovery 9 (3): 203–14. doi:10.1038/nrd3078. PMID 20168317.
• Sliwoski G, Kothiwale S, Meiler J, and. Lowe E. W. (2014) Computational Methods in Drug Discovery. Pharmacological Reviews. 66:334–395.
• Wikipedia: Drug Discovery