Unraveling the importance of the malaria parasite helicases

Abstract

Malaria is a human parasitic disease caused by infection from Plasmodium species, particularly Plasmodium falciparum. Each year millions of people are infected with malaria and large numbers of deaths result due to this deadly infection. P. falciparum contains 14 chromosomes, nearly 5400 genes and a multistage life cycle in humans and mosquitoes. The control of malaria is still a challenge as the parasite is continuously developing resistance to available antimalarial drugs and the mosquito vector is developing resistance to insecticides. The availability of P. falciparum genome has resulted in the identification of parasite‐specific proteins that can be targeted without harmful effects to the human host. Toward this goal, we have been working on the identification and characterization of helicases in order to find parasite‐specific helicases, which can be used as novel drug targets to tackle the rising problem of drug resistance. Helicases are ATP‐dependent nucleic acid unwinding enzymes. The P. falciparum genome analysis depicts that it contains some parasite‐specific helicases and homologs to most of the human helicases. Here, we present an overview of P. falciparum helicases and their importance in parasite growth and survival.

The Human Replicative Helicase, the CMG Complex, as a Target for Anti-cancer Therapy

“…Genome analyses have revealed that P. falciparum contains several parasite-specific helicases in addition to homolog of human helicases. Development of inhibitors that specifically target the helicases unique to P. falciparum would help to cure malaria (Tuteja, 2017 ).…”

Plasmodium falciparum specific helicase 3 is nucleocytoplasmic protein and unwinds DNA duplex in 3′ to 5′ direction

“…Due to this increasing resistance towards modern day front line antimalarials there is an urgent need to develop new range of antimalarial drugs and to identify novel chemotherapeutic targets 9 . Helicases are ubiquitous and present in every organism such as bacteria, virus, yeast, plants, human, and the malaria parasite Plasmodium 10 , 11 . Significant part of our genome encodes helicases, which proves the importance of these molecules 12 .…”

Introduction to the Special Issue on Malaria

“…This Special Issue on Malaria brings together cutting‐edge research and timely review articles to present a current overview of this expansive field. In this issue, five experts review key topics in malaria research, including the progress toward vaccine development , the problem of drug resistance , the artemisinin‐based combination therapy , the importance of helicases in malaria parasite biology , and the use of malarial proteases as viable drug targets . Four original studies from highly active malaria research groups present groundbreaking work on the P. falciparum ‐specific iron‐sulfur [Fe‐S] assembly pathway , characterization of an immunogenic P. falciparum surface protein for vaccine development , identification of amino acid substitutions that underlie metabolic adaptation in a P. falciparum mono‐acid transporter , and identification of origins of replication in the P. falciparum genome .…”

“…The review also discusses the efficiency of different ACTs compared to the usage of the partner drugs alone . The fourth review of the series highlights the helicases present in the P. falciparum genome . Helicases are motor proteins that play vital roles in nucleic acid unwinding by harnessing the energy derived from ATP hydrolysis.…”

“…In this review, we highlight the various families of helicases, their structure–function relationships, and their importance for malaria parasite growth and survival. We also propose suitable helicases that could be targets for antimalarial drugs . In the last review of the series, Edgar Deu describes the role of proteases in Plasmodium biology especially in P. falciparum .…”