Korupensamine A, but not its atropisomer, korupensamine B, inhibits SARS-CoV-2 in vitro by targeting its main protease (Mpro)

By combining docking and molecular dynamics simulations, we explored a library of 65 mostly axially chiral naphthylisoquinoline alkaloids and their analogues, with most different molecular architectures and structural analogues, for their activity against SARS-CoV-2. Although natural biaryls are often regarded without consideration of their axial chirality, they can bind to protein targets in an atroposelective manner. By combining docking results with steered molecular dynamics simulations, we identified one alkaloid, korupensamine A, that atropisomer-specifically inhibited the main protease (Mpro) activity of SARS-CoV-2 significantly in comparison to the reference covalent inhibitor GC376 (IC50 = 2.52 ± 0.14 and 0.88 ± 0.15 μM, respectively) and reduced viral growth by five orders of magnitude in vitro (EC50 = 4.23 ± 1.31 μM). To investigate the binding pathway and mode of interaction of korupensamine A within the active site of the protease, we utilized Gaussian accelerated molecular dynamics simulations, which reproduced the docking pose of korupensamine A inside the active site of the enzyme. The study presents naphthylisoquinoline alkaloids as a new class of potential anti-COVID-19 agents. Graphical abstract Image 1

Korupensamine A, but not its atropisomer, korupensamine B, inhibits SARS-CoV-2 in vitro by targeting its main protease (Mpro).

By combining docking and molecular dynamics simulations, we explored a library of 65 mostly axially chiral naphthylisoquinoline alkaloids and their analogues, with most different molecular architectures and structural analogues, for their activity against SARS-CoV-2. Although natural biaryls are often regarded without consideration of their axial chirality, they can bind to protein targets in an atroposelective manner. By combining docking results with steered molecular dynamics simulations, we identified one alkaloid, korupensamine A, that atropisomer-specifically inhibited the main protease (Mpro) activity of SARS-CoV-2 significantly in comparison to the reference covalent inhibitor GC376 (IC50 = 2.52 ± 0.14 and 0.88 ± 0.15 µM, respectively) and reduced viral growth by five orders of magnitude in vitro (EC50 = 4.23 ± 1.31 µM). To investigate the binding pathway and mode of interaction of korupensamine A within the active site of the protease, we utilized Gaussian accelerated molecular dynamics simulations, which reproduced the docking pose of korupensamine A inside the active site of the enzyme. The study presents naphthylisoquinoline alkaloids as a new class of potential anti-COVID-19 agents.

Electrochemical diagnostics of infectious viral diseases: Trends and challenges.

Infectious diseases caused by viruses can elevate up to undesired pandemic conditions affecting the global population and normal life function. These in turn impact the established world economy, create jobless situations, physical, mental, emotional stress, and challenge the human survival. Therefore, timely detection, treatment, isolation and prevention of spreading the pandemic infectious diseases not beyond the originated town is critical to avoid global impairment of life (e.g., Corona virus disease - 2019, COVID-19). The objective of this review article is to emphasize the recent advancements in the electrochemical diagnostics of twelve life-threatening viruses namely - COVID-19, Middle east respiratory syndrome (MERS), Severe acute respiratory syndrome (SARS), Influenza, Hepatitis, Human immunodeficiency virus (HIV), Human papilloma virus (HPV), Zika virus, Herpes simplex virus, Chikungunya, Dengue, and Rotavirus. This review describes the design, principle, underlying rationale, receptor, and mechanistic aspects of sensor systems reported for such viruses. Electrochemical sensor systems which comprised either antibody or aptamers or direct/mediated electron transfer in the recognition matrix were explicitly segregated into separate sub-sections for critical comparison. This review emphasizes the current challenges involved in translating laboratory research to real-world device applications, future prospects and commercialization aspects of electrochemical diagnostic devices for virus detection. The background and overall progress provided in this review are expected to be insightful to the researchers in sensor field and facilitate the design and fabrication of electrochemical sensors for life-threatening viruses with broader applicability to any desired pathogens.

Bioactivity Potential of Marine Natural Products from Scleractinia-Associated Microbes and In Silico Anti-SARS-COV-2 Evaluation.

Marine organisms and their associated microbes are rich in diverse chemical leads. With the development of marine biotechnology, a considerable number of research activities are focused on marine bacteria and fungi-derived bioactive compounds. Marine bacteria and fungi are ranked on the top of the hierarchy of all organisms, as they are responsible for producing a wide range of bioactive secondary metabolites with possible pharmaceutical applications. Thus, they have the potential to provide future drugs against challenging diseases, such as cancer, a range of viral diseases, malaria, and inflammation. This review aims at describing the literature on secondary metabolites that have been obtained from Scleractinian-associated organisms including bacteria, fungi, and zooxanthellae, with full coverage of the period from 1982 to 2020, as well as illustrating their biological activities and structure activity relationship (SAR). Moreover, all these compounds were filtered based on ADME analysis to determine their physicochemical properties, and 15 compounds were selected. The selected compounds were virtually investigated for potential inhibition for SARS-CoV-2 targets using molecular docking studies. Promising potential results against SARS-CoV-2 RNA dependent RNA polymerase (RdRp) and methyltransferase (nsp16) are presented.