Back to nature using herbal medicine has various beneficial effects viz; natural, non-toxic, availability and reduced side effects. Plant-based products contain numerous bioactive compounds that can work on affected targets to induce pharmacological responses to eliminate or reduce the ill effects caused by parasites. Extracts (methanolic or aqueous) derived from plant-organs (seeds or leaves, whole plant) having various naturally occurring compounds (terpenes, sesquiterpenes, phenolics etc) can potentially target different groups of parasitic organisms and vectors such as insects and arachnids. Medicinal plants and their derived medicines are modern society's most popular and widely used natural alternatives to synthetic chemicals. Since people face problems with synthetic medicines owing to their adverse side effects (vomiting, nausea, diarrhea, edema etc.), limited therapy, and emerging resistance to parasites, the new treatment methods are effective against parasites and pose less threat than commercial drugs. Hence, there has been a rapid development of herbal medicines in the last few decades (Wink, 2012, Sofowora et al., 2013, Perry, 2014, Ashby and Boots, 2015, Cholewinski et al., 2015; Wyk and Wink, 2017; Ohashi et al., 2018; Singh and Sharma, 2019; Awotedu et al., 2020; Jindal and Seth, 2022; Ramlal et al., 2023a).

Many parasitic diseases like malaria and leishmaniasis are responsible for health issues in people around the world. Many human infections are caused by endoparasites, which affect over 30% of the human population with a tremendous burden in the tropics, subtropics as well as in temperate climates in both developing and developed countries. Many human infections are caused by endoparasites, which affect over 30% of the human population. These include protozoa, nematodes, trematodes, and cestodes transmitted by arthropod vectors. Usually, a parasite won't eliminate its host immediately. However, they either undermine our health (most internal parasites) or become unpleasant (like lice and fleas). Protozoan diseases represent a critical health threat to tropical and subtropical countries. Parasitic diseases like malaria, trypanosomiasis, Chagas, and amoebiasis are deadly and are the reason for about one million deaths per year due to inadequate therapeutics (Perry, 2014, Ashby and Boots, 2015, Ohashi et al., 2018, Awotedu et al., 2020, El Sayed and Egbuna, 2021).

As co-evolution happens, humans and parasitic organisms have evolved better strategies to combat each other’s defensive mechanisms. As a result, parasitic organisms continuously modify their genetic constitution to survive better in the environment (Perry, 2014, Ashby and Boots, 2015, Ohashi et al., 2018, Awotedu et al., 2020).

Parasitic infections in humans represent one of the leading public health concerns since the treatment for internal parasites is more intricate as vaccination can hardly control them (Wink, 2012). Infections caused by protozoans such as Trypanosoma, Plasmodium, and Leishmania are significant problems that cause deaths globally. Hence, neglected tropical diseases like leishmaniasis, Chagas disease, and Human African Trypanosomiasis are among the most important diseases caused by trypanosomatids (Vaz, 2017).

Plasmodium, a single-celled protozoan, is the causative agent of malaria, and its transmittance in humans occurs by the vector, Anopheles mosquito. Certain malaria-causing species of Plasmodium in humans include Plasmodium falciparum (thereon P. falciparum), P. vivax, P. malariae, P. ovale and P. knowlesi. The most virulent parasite in Africa is the P. falciparum, which accounts for deaths globally. According to the World Health Organisation (WHO), about 53% of P. vivax cases are found principally in Southeast Asian countries, with a majority of 47% cases in India, followed by 75% of cases in the USA (WHO, 2019).

Malaria is one of the oldest, most dreadful, and deadliest diseases, causing deaths globally. Fatalities rose by 6% from around 227 million to 241 million cases reported in 2020 (Krungkrai and Krungkrai, 2016, Rosenthal, 2022). The African region reported having the highest number of deaths, with 213 million cases (93%) of malaria, followed by 3.4% and 2.1% of cases in the Southeast Asia and Eastern Mediterranean regions, respectively-19 countries, including India, account for almost 85% of all malaria cases occurring worldwide. Above 50% of the cases were reported from Nigeria (25%) alone, followed by the Democratic Republic of the Congo contributing 12% of cases, Uganda contributing 5% of cases, and Côte d'Ivoire, Mozambique, and Niger contributing 4% of cases each. Of these 19 countries, India reported significant absolute diminutions in malaria cases (WHO, 2019).

Over the years, P. falciparum has become resistant to standard treatments of antimalarial drugs such as chloroquine and other compounds in many parts of the globe. This is due to the extensive and prolonged practice of monotherapies, relying on a single active ingredient over many years against the parasite that accelerated the events of the development of resistance. So, this increases the multidrug-resistant strains of Plasmodium along with the dreadful side effects of the prevailing antimalarial drugs has commanded the exploration for a novel, well-tolerant, and more competent antimalarial drugs that can eliminate either the parasite or the vector (Shankar et al., 2011, Cholewinski et al., 2015, Siddiqui et al., 2022). Although significant progress has been made in this direction, identifying potent drugs against this parasite remains a considerable problem and challenge, especially in Africa (Rosenthal, 2022, Siddiqui et al., 2022).

Falcipain-2 (FP-2) is a type of cysteine protease hemoglobinase of erythrocytic Plasmodium falciparum parasites. The parasite's genome encodes cysteine proteases, including four cathepsin L-like papain-family proteases collectively known as falcipains. The disruption of this protein leads to the reduction of hemoglobin in the parasite. Inhibitors of FP-2 block hydrolysis of hemoglobin and thus arrest parasite development (Greenbaum et al., 2002, Kerr et al., 2009, Ettari et al., 2010, Rajguru et al., 2022). Phosphoethanolamine methyltransferase (PMT) belongs to the transferases enzymes family and participates in glycerophospholipid metabolism. This enzyme is absent in humans and provides an excellent target against the parasite. The inhibitors of such enzymes could contribute to the disruption of parasite biological processes and hence could act as an antimalarial drug (Lee et al., 2012, Bobenchik et al., 2013, Singh et al., 2019, El Rhabori et al., 2022).

A wide array of plants has been identified as a potential source of inhibitors against these microbes. Extracts formulated from different plant organs extract various antimalarial agents (phytochemicals). Different phytochemicals or secondary metabolites, like phenolics, flavonoids, alkaloids, terpenes, and lignans, extracted from various plant parts, possess antimalarial activity against Plasmodium species. Therefore, exploiting plant-based active constituents can be considered favorable for developing novel antimalarial drugs with refined efficiency, safety, and cost-effectiveness. Among other compounds, quinines and artemisinins are the two most reassuring groups of plant-based antimalarial compounds. Even WHO promotes artemisinin (and its derivatives) combination therapy due to its sophisticated effectiveness (Ekasari et al., 2019, Hailesilase et al., 2020; WHO, 2019). There is a need to switch and find alternative natural sources with promising health-promoting benefits and no side effects.

Soybean (Glycine max (L.) Merr.) is a nutritious and medicinally important legume containing a wide range of macro and micro molecules and a plethora of health-promoting compounds (Rajendran and Lal, 2020, Kumar et al., 2022, Rajendran et al., 2022, Ramlal et al., 2022a). It reduces and lowers hypertension and obesity. It shows anti-cholesterol activity (reduces the risk of CVD) and other diseases such as osteoporosis (Chen et al., 2012). Besides these, soybeans are also known for their antimicrobial (Ku et al., 2020) and antiplasmodic abilities (Deharo et al., 1995, Nyandwaro et al., 2020). Therefore, soybeans can be considered a potential medicinal crop due to the therapeutic value of their phytochemicals.

There are limited studies describing the role of soybeans in malaria, and to our knowledge, no study has reported the use of soy compounds against the parasite. The article aims to emphasize and identify novel inhibitors that could act against the malaria parasite. Soy compounds were searched for their activity against some of the crucial proteins of P. falciparum, namely phosphoethanolamine methyltransferase (PMT) and falcipain-2 (FP-2), which are involved in the biosynthesis of phosphocholine and hemoglobin hydrolysis respectively in the parasite through in silico and molecular simulation analyses. This study would eventually be helpful in the identification and development of novel and safer drug candidates for the parasite.