Evaluation of antiviral activity of Carica papaya leaves against SARS-CoV-2 assisted by metabolomic profiling.

The COVID-19 pandemic caused a huge health crisis all over the globe. SARS-CoV-2 is the virus responsible for the disease and it is highly contagious leaving millions of confirmed infected cases and a dangerous death toll. Carica papaya is a tropical plant known for its antiviral activity since it possesses different classes of compounds that are believed to combat various viral classes. In this study, the extracts prepared from C. papaya leaves cultivated in Egypt were evaluated for their anti-SARS-CoV-2 activity using crystal violet assay and for their cytotoxicity through MTT assay. The total methanolic extract, n-hexane, ethyl acetate, and n-butanol fractions of papaya leaves were used in the study and the results revealed that the n-hexane fraction has a high anti-SARS-CoV-2 activity with an IC50 value = 1.98 µg mL-1. Moreover, it also showed a high selectivity index value = 104.7. Dereplication of the secondary metabolites in the crude methanolic extract of C. papaya leaves revealed the presence of different classes of compounds including sterols, terpenes, fatty acid, alkaloids and flavonoids that are known to possess antiviral activities against various classes of viruses. The current study was assisted by molecular docking, molecular dynamics simulation and MM-PBSA calculations for the annotated compounds against 6 SARS-CoV-2 target proteins. The results of these in silico-based investigations showed high to moderate binding on the targeted proteins. This postulation may instigate further research studies concerning the compounds responsible for this high anti-SARS-CoV-2 activity of the n-hexane fraction of C. papaya leaves.

Design, Synthesis, Antiviral Evaluation, and Molecular Dynamics Simulation Studies of New Spirocyclic Thiopyrimidinones as Anti HCoV-229E.

The current pandemic threat presented by viral pathogens like SARS-CoV-2 (COVID-19) suggests that virus emergence and dissemination are not geographically confined. As a result, the quest for antiviral agents has become critical to control this pandemic. In the current study, we provide a novel family of spirocyclic thiopyrimidinone derivatives whose cytotoxicity and antiviral efficacy were investigated against human coronavirus 229E (HCoV-229E) as a model for the Coronaviridae family. We utilized MTT and cytopathic effect (CPE) inhibitory tests on green monkey kidney (vero-E6) cell lines. The new molecules showed varied degrees of antiviral activity against the vero-E6 cell lines with minimal cytotoxicity. With a high level of a selective index (SI=14.8), compound 9 showed outstanding inhibitory ability and could effectively suppress the human coronavirus 229E. Molecular dynamics simulation (MD) studies were performed to measure the interaction and stability of the protein-ligand complex in motion. The MD results for the most active compound 9 explored remarkable interactions with the binding pockets of the main protease (Mpro) of SARS-CoV-2 enzyme confirming the results gained from in vitro experiments. ADMET properties were also predicted for all the tested compounds. All these results demonstrated that the novel spirocyclic thiopyrimidinone derivatives would have the potential to be safe, low-cost chemical compounds that might be used as a novel therapeutic option for Coronaviridae viruses like COVID-19.