Identification of host factors that bind to the 5 ' end of the MERS-CoV RNA genome

Plain language summaryMERS-CoV is a virus that causes a severe illness in the nose, mouth and throat of humans. It is a zoonotic virus, which means that it can spread from animals to humans. MERS-CoV was first found in Saudi Arabia in 2012 and continues to pose a threat to public health. Interactions between the virus and human cells and proteins are important to establishing infection. Understanding these interactions is important for the development of drugs to treat viral infections. Here, we have identified some proteins that interact with MERS-CoV. Tweetable A proteomic approach for the identification of cellular proteins that interact with the 5 '-terminal region of MERS-CoV RNA genome. #MERS-CoV #RNA_viruses. Aim: The aim of this study was to identify host factors that interact with the 5 ' end of the MERS-CoV RNA genome. Materials & methods: RNA affinity chromatography followed by mass spectrometry analysis was used to identify the binding of host factors in Vero E6 cells. Results: A total of 59 host factors that bound the MERS-CoV RNA genome in non-infected Vero E6 cells were identified. Most of the identified cellular proteins were previously reported to interact with the genome of other RNA viruses. We validated our mass spectrometry results using western blotting. Conclusion: These data enhance our knowledge about the RNA-host interactions of coronaviruses, which could serve as targets for developing antiviral therapeutics against MERS-CoV.

In Silico Mining of Terpenes from Red-Sea Invertebrates for SARS-CoV-2 Main Protease (M^pro) Inhibitors

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent for the COVID-19 pandemic, which generated more than 1.82 million deaths in 2020 alone, in addition to 83.8 million infections. Currently, there is no antiviral medication to treat COVID-19. In the search for drug leads, marine-derived metabolites are reported here as prospective SARS-CoV-2 inhibitors. Two hundred and twenty-seven terpene natural products isolated from the biodiverse Red-Sea ecosystem were screened for inhibitor activity against the SARS-CoV-2 main protease (M^pro) using molecular docking and molecular dynamics (MD) simulations combined with molecular mechanics/generalized Born surface area binding energy calculations. On the basis of in silico analyses, six terpenes demonstrated high potency as M^pro inhibitors with DELTAG_binding <= -40.0 kcal/mol. The stability and binding affinity of the most potent metabolite, erylosides B, were compared to the human immunodeficiency virus protease inhibitor, lopinavir. Erylosides B showed greater binding affinity towards SARS-CoV-2 M^pro than lopinavir over 100 ns with DELTAG_binding values of -51.9 vs. -33.6 kcal/mol, respectively. Protein-protein interactions indicate that erylosides B biochemical signaling shares gene components that mediate severe acute respiratory syndrome diseases, including the cytokine- and immune-signaling components BCL2L1, IL2, and PRKC. Pathway enrichment analysis and Boolean network modeling were performed towards a deep dissection and mining of the erylosides B target-function interactions. The current study identifies erylosides B as a promising anti-COVID-19 drug lead that warrants further in vitro and in vivo testing.