Chikungunya fever in Africa: a systematic review
PATHOGENS AND GLOBAL HEALTH
Authors: Russo, Gianluca; Subissi, Lorenzo; Rezza, Giovanni
Since the identification of chikungunya virus (CHIKV), sporadic cases and outbreaks were reported in several African countries, on the Indian subcontinent, and in south-east Asia. In the last 20 years, there is a growing number of reports of CHIKV infections from African countries, but the overall picture of its circulation at the continent level remains ill-characterized because of under-diagnosis and under-reporting. Moreover, the public health impact of the infection in Africa is generally poorly understood, especially during outbreak situations. Our work has the aim to review available data on CHIKV circulation in Africa to facilitate the understanding of underlying reasons of its increased detection in the African continent.
Development of a theoretical model for the inhibition of nsP3 protease of Chikungunya virus using pyranooxazoles
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
Authors: Kumar, Durgesh; Kumari, Kamlesh; Jayaraj, Abhilash; Singh, Prashant
Chikungunya virus (CHIKV) causes Chikungunya fever (CHIKF) and till date no effective medicine for its cure is available in market. Different research groups find various possible interactions between small molecules and non-structural proteins, viz. nsP3, one of the most important viral elements in CHIKV. In this work, authors have studied the interactions of nsP3 protease of CHIKV with pyranooxazoles. Initially, a one-pot three-component reaction was designed using oxazolidine-2,4-dione, benzaldehyde and cyanoethylacetate to get a proposed biological active molecule, i.e. based on pyranooxazoles. The mechanism for the synthesis of the product based on pyranooxazole was studied through density functional theory (DFT) using Gaussian. Then, a library of the obtained pyranooxazole was created through computational tools by varying the substituents. Further, virtual screening of the designed library of pyranooxazoles (200 compounds) against nsP3 protease of CHIKV was performed. Herein, CMPD 104 showed strongest binding affinity toward the targeted nsP3 protease of CHIKV, based on the least binding energy obtained from docking. Based on docking results, the pharmacological, toxicity, biological score and Lipinski's filters were studied. Further, DFT studies of top five compounds were done using Gaussian. Molecular dynamics (MD) simulation of nsP3 protease of CHIKV with and without 104 was performed using AMBER18 utilizing ff14SB force field in three steps (minimization, equilibration and production). This work is emphasized to designing of one-pot three-component synthesis and to develop a theoretical model to inhibit the nsP3 protease of CHIKV.