**Abstract**

Malaria is a deadly disease caused by the plasmodium parasites. Approximately 210 million people get affected by malaria every year resulting in half a million deaths. Among several species of the parasite, *Plasmodium falciparum* is the primary cause of severe infection and death. Several drugs are available for malaria treatment in the market but plasmodium parasites have successfully developed resistance against many drugs over the years. This poses a serious threat to efficacy of the treatments and continuing discovery of new drug is necessary to tackle the situation, especially due to failure in designing an effective vaccine. People are now trying to design new drugs for malaria using AI technologies which can substantially reduce the time and cost required in classical drug discovery programs. In this chapter, we provide a comprehensive overview of a road map for several AI based computational techniques which can be implemented in a malaria drugs discovery program. Classical computers has limiting computing power. So, researchers are also trying to harness quantum machine learning to speed up the drug discovery processes.

**Keywords:** Malaria, *Plasmodium falciparum*, machine learning, drug design, Quantum machine learning, Topological data analysis

#### **1. Introduction**

Malaria is an infectious and dreadful disease caused by the plasmodium parasites. The parasite is transmitted to humans through the bites of infected mosquitoes. Around 210 million people get infected by malaria every year resulting in 440,000 deaths, especially children under the age of five [1]. The *Plasmodium falciparum* is the primary cause of severe infection and death in most cases. So far, numerous drugs are available in the market such as Quinine, Mepacrine, Chloroquine, Mefloquine, Halofantrine, Artemisinin and their derivatives. Unfortunately, malaria parasites, especially the falciparum species, developed resistance against many of these drugs if not all after some time posing a serious threat to the medication's efficacy [2]. As a result, the continued discovery of new drugs against malaria becomes essential to mitigate this threat. During the last decade, various drug design programs focusing on malaria are initiated all over the world. Drug discovery is a time-consuming and complex process that can be broadly divided into four main phases: (i) the target selection and validation, (ii) screening and optimization of lead compounds, (iii) preclinical studies, and (iv) clinical trials. First, the targets associated with specific diseases need to be identified. This

requires an evaluation of cellular and genetic targets, genomics and proteomics analysis, and prediction bioinformatics. The next step was to hit identification. The compound is identified from the library Molec-snake using combinatorial chemistry, high-throughput screening, and virtual screening. Furthermore, in vivo pharmacokinetic studies are performed to conduct toxicity tests on animals. After, the preclinical tests are conducted successfully, clinical trials are performed on the infected patients. Clinical trial is conducted in three phases. The Phase I constitutes drug safety test with few people; In Phase II, the dose amount of the drug necessary to eliminate the infection is determined on few patients and finally Phase III comprises of precisely quantifying the efficacy of the drug on large number of patients. After the drug candidates'safety and efficacy are confirmed in the clinical phases, agencies such as the FDA review this compound for approval and commercialization. The total cost of a conventional drug development pipeline is projected to be USD 2.6 billion, and it can take more than 12 years for a complete traditional workflow.

### **2. Malaria disease overview**

Malaria has a wide effect in the subtropical and tropical continents. Sub-Saharan Africa has the most malaria cases as well as significant cases in India, Brazil, Afghanistan, Sri Lanka, Thailand, Indonesia, Vietnam, Cambodia, and China [3, 4]. In many medium climate areas, such as Western Europe and the United States, public health measures and economic development have succeeded in achieving elimination of malaria, apart from occasionally imported cases through international travels. Female Anopheles mosquitoes transmit malaria. There are approximately 400 species of Anopheles in the world. Among them, 30 species are responsible for malaria. Plasmodium species can also infect animals, birds, etc. The four species of malaria parasites namely *Plasmodium falciparum*, *Plasmodium vivax*, Plasmodium ovale and Plasmodium malariae, can infect humans under natural conditions. *Plasmodium falciparum* is the major killer among these species. In August 1897, Ronald Ross for first time reported that the parasites can infect female mosquitoes and further showed that the parasite completed it's development cycle in the female mosquitoes which is the primary source of the spread of infection from one infected patient to another healthy individual.

#### **2.1 Life cycle**

Malaria infection begins when the anopheles mosquito bites someone and injects plasmodium parasitse into the bloodstream in the form of sporozoites. Sporozoites are then passed to the human liver and multiply asexually in liver cells for the next 7 to 10 days, but do not cause any symptom. In animals, parasites are released from liver cells to the vesicles in the form of merozoites which then enter into the heart and in the lungs and finally stays in the lung capillary.

The vesicles eventually disintegrate, enabling the merozoites to progress to the blood stage of development. Merozoites enter red blood cells (erythrocytes) in the bloodstream and multiply until the cells burst [5] resulting in released merozoites which further penetrate more erythrocytes. Each time parasites invade the blood cells, this cycle is repeated, causing fever. Some parasites inside the infected blood cells leave the asexual multiplication cycle [6]. Instead of replicating, these parasites in those blood cells develop into sexual forms of parasites, called gametocytes flowing through the bloodstream. When an anopheles mosquito bites an infected human, it swallows the gametocytes, which develop further into mature sex cells

*Drug Design for Malaria with Artificial Intelligence (AI) DOI: http://dx.doi.org/10.5772/intechopen.98695*

**Figure 1.**

*Malaria parasite life cycle. This pictute is downloaded from (https://www.ncbi.nlm.nih.gov/books/NBK5951/f igure/malaria\_LifeCycle/).*

called gametes [7]. The female gametes that have been fertilized grow into actively moving ookinetes which form oocysts outside the surface. Thousands of active sporozoites develop within the oocyst and eventually, the oocyst bursts, releasing sporozoites into the body's cavity that fly to the salivary glands of the mosquito [8]. As the mosquito bites another person injecting the sporozoites the cycle of human infection begins again (**Figure 1**).
