The researchers have developed an end-to-end drug discovery pipeline for malaria by using the next generation artificial intelligence (AI).
Malaria is one of the oldest infectious diseases in the world that still causes many health problems in many tropical countries, according to a study published in the journal Scientific Reports.
Plasmodium falciparum, the most dangerous parasite of human malaria, is believed to cause hundreds of millions of diseases and about half a million deaths a year, researchers from Insilico Medicine Taiwan said.
Plasmodium falciparum causes malaria in humans by destroying human hemoglobin by falcipain-2 (FP2).
FP2 inhibitors block the breakdown of hemoglobin and parasite development, suggesting that FP2 inhibition is a promising target for antimalar therapy, the researchers said.
Malaria control has been hampered by increasing malaria parasite resistance to available medicines, they said.
New antimalar drugs are urgently needed, ideally directed against new targets.
To cope with this challenge, researchers at Insilico Taiwan have extensively studied the mechanisms by which the E64 protease inhibitor approaches, interacts with and inhibits FP2.
The efficacy of E64, its mechanism of action and the potential of E64 derivatives to have low toxicity in humans makes E64 and its potential derivatives as drugs to treat diseases with high levels of cysteine proteases as a primary cause.
The results of the study have shown that binding of E64 and FP2 is facilitated by FP2 amino acids located within and near the previously identified binding pocket of FP2.
This suggests that antimalarial drug design should not just focus on finding candidates for drugs that will bind tightly to pocket scraps, but also takes into account the need for the drug candidate to be able to link to the debris around pocket sub-sites set.
"Insilico Taiwan is pleased to present the work on malaria that can help save millions of lives," said Artur Kadurin, CEO of Insilico Medicine Taiwan.
The results of the study confirm that E64 is able to inhibit FP2 and explain in detail the physico-chemical factors of the E64 interaction with FP2 as being extremely favorable.