The reemergence of coronavirus prompts the need for the development of effective therapeutics to prevent the cellular entry and replication of coronavirus. This study demonstrated the putative inhibitory potential of lopinavir, remdesivir, oseltamir, azithromycin, ribavirin, and chloroquine towards V-ATPase, protein kinase A, SARS-CoV spike glycoprotein/ACE-2 complex and viral proteases. The pharmacodynamic and pharmacokinetic properties were predicted through the pkCSM server while the corresponding binding affinity of the selected drugs towards the proteins was computed using AutodockVina Screening tool. The ADMET properties revealed all the drugs possess drug-like properties. Lopinavir has the highest binding affinities to the pocket site of SARS-CoV spike glycoprotein/ ACE-2 complex, cyclic AMP-dependent protein kinase A and 3-Chymotrypsin like protease while redemsivir has the highest binding affinities for vacuolar proton-translocating ATPase (V-ATPase) and papain-like proteins. The amino acids Asp269, Leu370, His374, and His345 were predicted as the key residues for lopinavir binding to human SARS-CoV spike glycoprotein/ACE-2 complex while His378, Tyr515, Leu73, Leu100, Phe32 and Phe40 for remdesivir and Tyr510, Phe504, Met62, Tyr50, and His378 were predicted for azithromycin as the key residues for binding to SARS-CoV spike glycoprotein/ACE-2 complex. Moreover, it was also observed that chloroquine has appreciable binding affinities for 3-Chymotrpsin-like protease and cyclic AMP-dependent protein kinase A when compared to Oseltamivir and ribavirin. The study provided evidence suggesting putative repurposing of the selected drugs for the development of valuable drugs for the prevention of cellular entry and replication of coronavirus. ARTICLE HISTORY
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The global challenge to the treatment of malaria is mainly the occurrence of resistance of malaria parasites to conventionally used antimalarials. Artesunate, a semisynthetic artemisinin compound, and other artemisinin derivatives are currently used in combination with selected active antimalarial drugs in order to prevent or delay the emergence of resistance to artemisinin derivatives. Several methods, such as preparation of hybrid compounds, combination therapy, chemical modification and the use of synthetic materials to enhance solubility and delivery of artesunate, have been employed over the years to improve the antimalarial activity of artesunate. Each of these methods has advantages it bestows on the efficacy of artesunate. This review discussed the various methods employed in enhancing the antimalarial activity of artesunate and delaying the emergence of resistance of parasite to it.
With the world threatened by a second surge in the number of Coronavirus cases, there is an urgent need for the development of effective treatment for the novel coronavirus (COVID-19). Recently, global attention has turned to preliminary reports on the promising anti-COVID-19 effect of histamine H2-receptor antagonists (H2RAs), most especially Famotidine. Therefore, this study was designed to exploit a possible molecular basis for the efficacy of H2RAs against coronavirus. Molecular docking was performed between four H2RAs, Cimetidine, Famotidine, Nizatidine, Ranitidine, and three non-structural proteins viz. NSP3, NSP7/8 complex, and NSP9. Thereafter, a 100 ns molecular dynamics simulation was carried out with the most outstanding ligands to determine the stability. Thereafter, Famotidine and Cimetidine were subjected to gene target prediction analysis using HitPickV2 and eXpression2Kinases server to determine the possible network of genes associated with their anti-COVID activities. Results obtained from molecular docking showed the superiority of Famotidine and Cimetidine compared to other H2RAs with a higher binding affinity to all selected targets. Molecular dynamic simulation and MMPBSA results revealed that Famotidine as well as Cimetidine bind to non-structural proteins more efficiently with high stability over 100 ns. Results obtained suggest that Famotidine and Cimetidine could be a viable option to treat COVID-19 with a mechanism of action that involves the inhibition of viral replication through the inhibition of non-structural proteins. Therefore, Famotidineand Cimetidine qualify for further study as a potential treatment for COVID-19.
Objectives Glycoproteins are organic compounds formed from proteins and carbohydrates, which are found in many parts of the living systems including the cell membranes. Furthermore, impaired metabolism of glycoprotein components plays the main role in the pathogenesis of diabetes mellitus. The aim of this study is to investigate the influence of glycoprotein levels in the treatment of diabetes mellitus. Methods All relevant papers in the English language were compiled by searching electronic databases, including Scopus, PubMed and Cochrane library. The keywords of glycoprotein, diabetes mellitus, glycan, glycosylation, and inhibitor were searched until January 2019. Results Glycoproteins are pivotal elements in the regulation of cell proliferation, growth, maturation and signaling pathways. Moreover, they are involved in drug binding, drug transportation, efflux of chemicals and stability of therapeutic proteins. These functions, structure, composition, linkages, biosynthesis, significance and biological effects are discussed as related to their use as a therapeutic strategy for the treatment of diabetes mellitus and its complications. Conclusions The findings revealed several chemical and natural compounds have significant beneficial effects on glycoprotein metabolism. The comprehension of glycoprotein structure and functions are very essential and inevitable to enhance the knowledge of glycoengineering for glycoprotein-based therapeutics as may be required for the treatment of diabetes mellitus and its associated complications.
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