<p>A novel coronavirus (SARS-CoV-2) has been the cause of a recent pandemic of respiratory illness known as COVID-19. The lack of anti-viral drugs or vaccines to control the infection has resulted in an enormous number of seriously ill patients requiring hospitalization. In the absence of an effective vaccine, there is an urgent need for therapies which can fight COVID-19 infection. Readily available compounds in foods and plants may be one source of anti-viral compounds. Here, natural product chemicals from the Nuclei of Bioassays, Ecophysiology and Biosynthesis of Natural Products Database (NuBBE_DB) were screened against the main protease (Mpro) of SARS-CoV-2. This protease was chosen as a target due to its importance in the replication of SARS-CoV-2. Molecular docking was used to screen the natural products against Mpro to identify potential candidates. The identified candidates were further filtered using molecular dynamics simulation investigation. Nine natural compounds were identified for experimental validation, with carlinoside and quercetin 3-o-sophoroside being the top candidates. </p>

The final stage of endocytosis involves the recruitment of the protein dynamin to the neck of the vesicle to cut the membrane and release the vesicle to the interior of the cell. Dynamin forms a helical protein coat around the vesicle neck that ultimately disrupts the lipid membrane and the vesicle is released. Dynamin is able to causes membrane scission by undergoing a large conformational change after catalyzing the hydrolysis of guanosine triphosphate (GTP) to guanosine diphosphate (GDP), which results in an allosteric change in the protein structure. Understanding how the reaction energy released by the hydrolysis reaction is used by the protein to undergo conformational changes is key to determining the molecular mechanism of membrane fission. To this end, we have used molecular dynamics of dynamin monomers, dimers, and tetramers in solution to understand the free energy changes associated with allosteric conformation changes undergone by the protein. These studies will allow us to begin developing a new molecular based model of how dynamin is able to channel the energy released by GTP hydrolysis to remodel lipid membranes during dynamin induced membrane fission.