Dynamic protein and polypeptide hydrogels based on Schiff base co-assembly for biomedicine.

Stimuli-responsive biopolymer hydrogels are promising building blocks for biomedical devices, attributable to their excellent hydrophilicity, biocompatibility, and dynamic responsiveness to temperature, light, pH, and water content. Although hydrogels find interesting applications as drug carriers, therapeutic adhesives, scaffolds for tissue engineering, inks for bioprinting, and biosensors, conventional chemically crosslinked hydrogels often lack adaptive and biomimetic properties needed for diverse biomedical applications. Using dynamic and reversible crosslinks such as the Schiff base bond, biomimetic hydrogels featuring structurally dynamic behaviours, such as shape memory, self-healing properties, and dynamic mechanical resilience, can be developed for in vivo therapy. Natural proteins and polypeptides are non-toxic, biodegradable, and biocompatible biopolymers that serve fundamental structural and biochemical functions in the human body. Besides natural polypeptides, easily processible synthetic polypeptides are protein analogues with widely tunable sequences that form secondary structures. Therefore, natural proteins and synthetic polypeptides are excellent candidates for fabricating Schiff base-linked biomedical hydrogels. This review outlines the functional properties, design approaches, and applications of Schiff base-linked protein and polypeptide hydrogels in tissue engineering, regenerative medicine, wound dressing, drug delivery, bioprinting, and biosensors. The review ends with an outlook of future developments for potential applications of Schiff base-linked protein and polypeptide hydrogels in and beyond biomedicine.

Designed thiazolidines: an arsenal for the inhibition of nsP3 of CHIKV using molecular docking and MD simulations.

Chikungunya virus (CHIKV) belongs to the alpha virus and it's infection in humans causes fever, known as chikungunya fever (CHIKF). It is a sudden onset of fever and may affect humans badly. The mode of transmission to human occurs due to the biting of the mosquitoes. Till date, thousands of humans are affected from this virus throughout the world. As on date, no promising medicine or vaccine is available in the market to cure from this viral infection. Therefore, there is a need of promising candidate against the nsp3 of CHIKV. In the present work, a library of the compounds are designed based on the product obtained in a multi-component reaction. Then, the designed compounds are filtered based on binding energy against the nsp3 of CHIKV obtained using molecular docking. Further, to understand the interaction of nsp3 of CHIKV and screened compound, CMPD474, the molecular dynamics (MD) simulations at different temperatures, that is, 300, 325, 350, 375, and 400 K is performed. The binding or the formation of the complex is studied through different trajectories obtained from MD simulations. The accurate information for the binding energy is determined by performing MM-GBSA calculations and the best inhibition was observed at 300 K as the change in free energy for the formation of the complex is -7.0523 kcal/mol.Communicated by Ramaswamy H. Sarma.

Challenges with the proposed approach in enhancing the accessibility of antimalarial activities during COVID 19 pandemic.

COVID 19 has hardly left any part of the world untouched. Two hundred thirteen countries have been affected by this disease, with 17,208,324 cases and 670,626 deaths as of July 30, 2020. If we look at the death toll caused by Malaria, this year, it is closely nearing COVID 19 deaths, 5, 68,700 deaths. Malaria mostly occurs in poor, tropical, and subtropical regions across the globe. In 2018, Malaria was most rampant in Africa, followed by Southeast Asian Regions (SEAR). SEAR is at the greatest risk of both COVID 19 and malaria. Strategies for essential commodities and antimalarial activities are affected by COVID 19 when the rainy season registers the maximum malaria load. We searched the literature to explore the evidence regarding efficacious antimalarial activities and the gap created by the COVID 19 pandemic, responsible barriers, and challenges, with the possible approaches towards accomplishing a target for malaria control.

In-silico prediction of novel drug-target complex of nsp3 of CHIKV through molecular dynamic simulation.

Literature reported that nsp3 of CHIKV is an important target for the designing of drug as it involves in the replication, survival etc. Herein, about eighteen million molecules available in the ZINC database are filtered against nsp3 using RASPD. Top five hit drug molecules were then taken from the total screened molecules (6988) from ZINC database. Then, a one pot-three components reaction is designed to get the pyrazolophthalazine and its formation was studied using DFT method. Authors created a library of 200 compounds using the product obtained in the reaction and filtered against nsp3 of CHIKV based on docking using iGEMDOCK, a computational tool. Authors have studied the best molecules after applying the the Lipinski's rule of five and bioactive score. Further, the authors took the best compound i.e. CMPD178 and performed the MD simulations and tdMD simulations with nsp3 protease using AMBER18. MD trajectories were studied to collect the information about the nsp3 of CHIKV with and without screened compound and then, MM-GBSA calculations were performed to calculate change in binding free energies for the formation of complex. The aim of the work is to find the potential candidate as promising inhibitor against nsp3 of CHIKV.