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The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) from China has become a global threat due to the continuous rise in cases of Coronavirus disease 2019 (COVID-19). The problem with COVID-19 therapeutics is due to complexity of the mechanism of the pathogenesis of this virus. In this review, an extensive analysis of genome architecture and mode of pathogenesis of SARS-CoV-2 with an emphasis on therapeutic approaches is performed. SARS-CoV-2 genome consists of a single, ~29.9 kb long RNA having significant sequence similarity to BAT-CoV, SARS-CoV and MERS-CoV genome. Two-third part of SARS-Cov-2 genome comprises of ORF ( ORF1ab ) resulting in the formation of 2 polyproteins, pp1a and pp1ab, later processed into 16 smaller non-structural proteins (NSPs). The four major structural proteins of SARS-CoV-2 are the spike surface glycoprotein (S), a small envelope (E), membrane (M), and nucleocapsid (N) proteins. S protein helps in receptor binding and membrane fusion and hence plays the most important role in the transmission of CoVs. Priming of S protein is done by serine 2 transmembrane protease and thus plays a key role in virus and host cell fusion. This review highlights the possible mechanism of action of SARS-CoV-2 to search for possible therapeutic options.

The unexpected emergence of the new Coronavirus disease (COVID-19) has affected more than three hundred million individuals and resulted in more than five million deaths worldwide. The ongoing pandemic has underscored the urgent need for effective preventive and therapeutic measures to develop anti-viral therapy. The natural compounds possess various pharmaceutical properties and are reported as effective anti-virals. The interest to develop an anti-viral drug against the novel severe acute respiratory syndrome Coronavirus (SARS-CoV-2) from natural compounds has increased globally. Here, we investigated the anti-viral potential of selected promising natural products. Sources of data for this paper are current literature published in the context of therapeutic uses of phytoconstituents and their mechanism of action published in various reputed peer-reviewed journals. An extensive literature survey was done and data were critically analyzed to get deeper insights into the mechanism of action of a few important phytoconstituents. The consumption of natural products such as thymoquinone, quercetin, caffeic acid, ursolic acid, ellagic acid, vanillin, thymol, and rosmarinic acid could improve our immune response and thus possesses excellent therapeutic potential. This review focuses on the anti-viral functions of various phytoconstituent and alkaloids and their potential therapeutic implications against SARS-CoV-2. Our comprehensive analysis provides mechanistic insights into phytoconstituents to restrain viral infection and provide a better solution through natural, therapeutically active agents.

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One of the significant proteins that have attracted research groups due to virtue of being a potent selective anticancer drug target and property of triggering apoptosis upon release in cytoplasm is cytochrome c (cyt c). The mechanical transformations due to the macromolecular crowding in membrane in the mammalian cell are proposed to be useful inductors of changes in volume. It is very interesting to know that mitochondrial function were observed to be improved by polyethylene glycol (PEG) interaction, which in turn inhibits the cyt c (a pro-apoptotic cell death factor). In this work, the effect of polyethylene glycol of molecular weight 4 kilo Dalton (PEG 4 kDa) was investigated to highlight the structural transformations (tertiary and secondary structure) in cyt c using a choice of spectroscopic techniques (including UV–Vis absorption, near-UV, far-UV and Soret circular dichroism and fluorescence spectroscopy), which shows noteworthy shifts in the secondary and tertiary structures at higher concentrations of PEG 4 kDa with small changes in the heme-globular interactions. The size distribution changes of native protein treated with various concentrations of the crowder were observed and analyzed by dynamic light scattering (DLS). The interaction studies of the crowder with the protein was observed and analyzed by FTIR, isothermal titration calorimetry, time resolved fluorescence and molecular docking. The investigations suggested that the structural changes in the protein occurred due to soft interactions of PEG 4 kDa, which usually destabilizes proteins. The experimental evidence in this study proposed that crowding could be another approach to mechanical super-competition and free of certain markers that could aid in the identification and control of various diseases. This study suggests that crowders at specific concentrations, which softly interact with proteins, can be exploited as remedy for various diseases.