Targeting CLK3 with Covalent Inhibitors: A Novel Strategy for Malaria Treatment.

Malaria still causes over 600,000 deaths annually, with rising resistance to frontline drugs by increasing this number each year. New medicines with novel mechanisms of action are, therefore, urgently needed. In this work, we solved the cocrystal structure of the essential malarial kinase CLK3 with the reversible inhibitor TCMDC-135051 (), enabling the design of covalent inhibitors targeting a unique cysteine residue (Cys368) poorly conserved in the human kinome.

Prevalence and association between alcohol, tobacco, and COVID-19: a study from a tribal predominant district in eastern India.

Introduction: Alcohol and tobacco use has been proposed to significantly affect COVID-19 outcomes. The study aimed to estimate the prevalence of alcohol and tobacco use among COVID-19-positive patients and compare it with the general population prevalence rates. It also aimed to assess and determine the association between the severity of COVID-19 illness and the complications with alcohol and tobacco use.

To assess the prevalence of dental anxiety among patients visiting a teaching dental hospital in Lucknow, India and their self-perceived treatment needs.

Image 1 Patients self assessment was a good predictor of patient dental status.

New insights of falcipain 2 structure from Plasmodium falciparum 3D7 strain.

Malaria identifies as a tropical hallmark, conforming to the burgeoning notion of escalating drug resistance among virulent strains, with the burdensome Plasmodium falciparum under its wing. The cysteine protease Falcipain-2 (FP2) is released in the parasite's food vacuole in the trophozoite stage and contributes to disease progression through its hemoglobinase activity. In the present study, we have determined the crystal structure of FP2 from a drug resistant P.

Inhibition of Plasmodium falciparum cysteine protease falcipain-2 by a human cross-class inhibitor serpinB3: A mechanistic insight.

Falcipain-2(FP2), a cysteine protease from Plasmodium falciparum, cleaves host erythrocyte hemoglobin and specific membrane skeleton components during the parasite life cycle. Therefore its inhibition has been considered as an attractive approach to combat the disease. SerpinB3 (SPB3) belongs to the ovalbumin-serpin family and is a potent cross-class inhibitor of cysteine cathepsins L, K, S and papain.