Relaxed complex scheme and molecular dynamics simulation suggests small molecule inhibitor of human TMPRSS2 for combating COVID-19

This research article was published by Taylor & Francis online in 2021As the coronavirus disease 19 (COVID-19) pandemic continues to pose a health and economic crisis worldwide, the quest for drugs and/or vaccines against the virus continues. The human transmembrane protease serine 2 (TMPRSS2) has attracted attention as a target for drug discovery, as inhibition of its catalytic reaction would result in the inactivation of the proteolytic cleavage of the SARS-CoV-2 S protein. As a result, the inactivation prevents viral cell entry to the host’s cell. In this work, we screened and identified two potent molecules that interact and inhibit the catalytic reaction by using computational approaches. Two docking screening experiments were performed utilizing the crystal structure and holo ensemble structure obtained from molecular dynamics in bound form. There is enhancement and sensitivity of docking results to the holo ensemble as compared to the crystal structure. Compound 1 demonstrated a similar inhibition value to nafamostat by interacting with catalytic triad residues His296 and Ser441, thereby disrupting the already established hydrogen bond interaction. The stability of the ligand–TMPRSS2 complexes was studied by molecular dynamics simulation, and the binding energy was re-scored by using molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) binding free energy. The obtained compounds may serve as an initial point toward the discovery of potent TMPRSS2 inhibitors upon further in vivo validation

Preparation of activated carbon with disered properties through optimization of impregnating agent

This research articles was published in Research Journal of Applied Sciences, Engineering and Technology 2014In this study, activated carbon with desired properties was prepared from peanut shell and sugarcane bagasse using chemical activation method in which potassium hydroxide (KOH) was used as a impregnating agent. The properties of the activated carbon were evaluated based on the activation temperature, yield percentage, ratio of KOH to Char impregnation, and iodine adsorption number. Based on the characterization methods employed, the desired properties for activated carbon from peanut shell were obtained at these optimum conditions: Activation temperature of 350 0 C, treatment time of 1hr, and impregnation ratio of 1:2. These conditions exhibited maximum iodine number of 355 mg/g. On the other hand, sugarcane bagasse produced the superior properties (iodine number of 914.71 mg/g) at an activation temperature of 700 0 C, treatment time of 1hr, and impregnation ratio of 1:1. The activated carbons with superior properties obtained in this study are suitable for the treatment of waste water associated with carboxylic acids. Our on- going project will test the performance of the final product for various innovative application

Abrogating the nsp10–nsp16 switching mechanisms in SARS-CoV-2 by phytochemicals from Withania somnifera: a molecular dynamics study

This research article published by Taylor & Francis Online, 2021The search for therapeutic small molecules and vaccines for Covid-19 treatment is an urgent but evolving topic. The virus has claimed over 3,782,490 lives (as of 12 June 2021), with the figure expected to rise due to the high versatility of the SAR-CoV-2 variant. Therapeutic options based on SARS-CoV-2 inhibitor are essential. Withanolides have a long history in traditional medicines with versatile biological properties including antiviral activities. In this study, the inhibitory potential of withanolides from Withania somnifera (Ashwagandha) against SARS-CoV-2 non-structural protein 10 (nsp10) was investigated by employing atomistic in silico methods viz molecular docking, molecular dynamics and binding free energy calculations. Investigated Withania somnifera compounds demonstrated binding affinity to the nsp10 and in its complex form, that is, nsp10-nsp16 heterodimer. Two withanolides; withanoside IV and withanoside V isolated from the roots of Withania somnifera demonstrated strong inhibition with binding free energies of −29.5 and −29.1 kJ/mol, respectively. Molecular dynamics and binding free energy ascertained the stability of withanoside IV. Water molecules, although known to play an important role in mediating biological systems, herein, water was found to have a repulsive binding effect to some residues, suggesting that the binding of withanoside IV would require dewetting of the nsp10 or displacing the water to bulk solvents. Interestingly, residues in the nsp10 that are responsible for forming stable interaction at the nsp10–nsp16 were found to be strongly interacting with withanoside IV, hence weakening the nsp10–nsp16 interaction and recognition. Further in vitro and in vivo experiments are recommended to validate the anti-SARS-COV-2 potential of these phytochemicals

Luteolin: a blocker of SARS-CoV-2 cell entry based on relaxed complex scheme, molecular dynamics simulation, and metadynamics

This research article published by Springer Nature, 2021Natural products have served human life as medications for centuries. During the outbreak of COVID-19, a number of naturally derived compounds and extracts have been tested or used as potential remedies against COVID-19. Tetradenia riparia extract is one of the plant extracts that have been deployed and claimed to manage and control COVID-19 by some communities in Tanzania and other African countries. The active compounds isolated from T. riparia are known to possess various biological properties including antimalarial and antiviral. However, the underlying mechanism of the active compounds against SARS-CoV-2 remains unknown. Results in the present work have been interpreted from the view point of computational methods including molecular dynamics, free energy methods, and metadynamics to establish the related mechanism of action. Among the constituents of T. riparia studied, luteolin inhibited viral cell entry and was thermodynamically stable. The title compound exhibit residence time and unbinding kinetics of 68.86 ms and 0.014 /ms, respectively. The findings suggest that luteolin could be potent blocker of SARS-CoV-2 cell entry. The study shades lights towards identification of bioactive constituents from T. riparia against COVID-19, and thus bioassay can be carried out to further validate such observations