: The unprecedented pandemic of COVID-19 caused by the novel strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) engulfs millions of death worldwide. It has directly hit the socio-economic status of the affected countries. There are more than 219 countries badly affected by the COVID-19. There are no particular small molecule inhibitors to combat the dreadful virus. Many antivirals, antimalarials, antiparasitic, antibacterials, immunosuppressive anti-inflammatory, and immune stimulatory agents have been repurposed for the treatment of COVID19. But the exact mechanism of action of these drugs towards COVID-19 targets has not been experimented with yet. Under the effect of chemotherapeutics, the virus may change its genetic material and produces various strains, which are the main reasons behind the dreadful attack of COVID-19. The nuclear genetic components are composed of main protease and RNA-dependent RNA polymerase (RdRp) which are responsible for producing nascent virion and viral replication in the host cells. To explore the biochemical mechanisms of various small molecule inhibitors, structure-based drug design can be attempted utilizing NMR crystallography. The process identifies and validates the target protein involved in the disease pathogenesis by the binding of a chemical ligand at a well-defined pocket on the protein surface. In this way, the mode of binding of the ligands inside the target cavity can be predicted for the design of potent SARS-CoV-2 inhibitors.
Background: Hepatitis C Virus (HCV) belongs to the Hepacivirus family. HCV has been designated as a very dreadful virus as it can attack the liver causing inflammation and even may lead to cancer in chronic condition. It was es- timated that 71 million people around the world have chronic HCV infection. World Health Organization (WHO) reported that about 399000 people died because of chronic cirrhosis and liver cancer globally. In spite of abundance of availability of drugs for the treatment of HCV, however, the issue of drug resistance surpasses all the possibilities of therapeutic man- agement of HCV. Therefore, to address this issue of ‘drug-resistance’ various HCV targets were explored to quest the evaluation of the mechanism of the disease progression. Methods: An attempt has been made in the present study to explore the various targets of HCV involved in the mecha- nism(s) of the disease initiation and progression and to focus on the mode of binding of ligands, which are co-crystallized at the active cavity of different HCV targets. Conclusion: The present study could predict some crucial features of these ligands which possibly interacted with various amino acid residues responsible for their biological activity and molecular signaling pathway(s). Such binding mode may be considered as a template for the high throughput screening and designing of active congeneric ligands to combat HCV.
Objective: Hepatitis C Virus (HCV) is very dreadful as it can attack an estimated 71 million people around the world. The World Health Organization (WHO) reported that every year about 399000 people die due to HCV caused by chronic cirrhosis and liver cancer globally. There are many drugs available for the treatment of HCV. But drug resistance and toxicity are major issues. The quest for potential drugs utilizing repositioning would be a very useful and economical method to combat the HCV. Methods: One of the most HCV targets is RNA dependent RNA polymerase (RdRp). The RdRp is common in HCV, Dengue virus (DENV), Zika virus (ZIKV), and Yellow fever virus (YFV) belonging to the same family of Flaviviridae. An attempt has been made in the present study to repositioning different DENV, ZIKV, and YFV RdRp inhibitors against HCV NS5B polymerase utilizing structure-based molecular docking which explores the affinity and mode of binding of these RdRp inhibitors. Results: Several 87 compounds having dengue, yellow fever and zika RdRp inhibitory activities have been taken into consideration for the screening of potential RdRp leads utilizing docking simulation which focuses the affinity and mode of binding of sofosbuvir diphosphate which is a standard HCV, RdRp inhibitor. Conclusion: It was found that the compounds 6 (N-sulfonylanthranilic acid derivative), 17 (R1479), 20 (DMB220), 23 (FD-83-KI26), 40 (CCG-7648), 50 (T-1106), 65 (mycophenolic acid), and 69 (DMB213) can produce docking score with the range of -7.602 to -8.971 Kcal/Mol having almost same mode of interaction as compared to the reference drug molecule. The drugs mentioned above can produce satisfactory affinity to bind the hepatitis C viral RdRp and thus may be used to treat the disease. Therefore, these predicted compounds may be potential leads for further testing of anti HCV activity and can be repurposed to combat HCV. The high throughput shotgun of drug repurposing utilizing structure-based docking simulation freeware would be a cost-effective way to screen the potential anti-HCV leads.
Friction Stir welding (FSW) is a solid state attachment method used for welding of metals of same and different metals. This process of friction stir welding (FSW) is widely using for the reason it can produces sound welds and doesn't have common issues like solidification and liquefaction cracking connected to the fusion techniques. The Friction stir welding of Al 5086 alloys had been commercialized and up to date interest is targeted on change of integrity with different metals. Thus on commercialize this method, analysis studies are required to characterize. particularly, FSW has impressed researchers to aim modification of integrity different metals like aluminum 5086 that differ in properties and sound welds with none or restricted inter metallic bonding of components has been done. In this paper we have to make a research on the current analysis state of FSW between aluminum 5086 with attention on the resulting welding and tensile strength, microstructure, elongation and the tools are used to produce the welds and also an insight into future analysis during this process of study the project of friction welding. By this process in our project we got an idea of going to maintain the rotational speed (rpm) 450 to 1400 and also by changing welding rpm (speed). This friction stir welding is used in nasa for joining of two totally different or same types of materials.
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