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The novel coronavirus disease-2019 (COVID-19) that emerged in China, is an extremely contagious and pathogenic viral infection caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) that has sparked a global pandemic. The few and limited availability of approved therapeutic agents or vaccines is of great concern. Urgently, Remdesivir, Nirmatrelvir, Molnupiravir, and some phytochemicals including polyphenol, flavonoid, alkaloid, and triterpenoid are applied to develop as repurposing drugs against the SARS-CoV-2 invasion. This study was conducted to perform molecular docking and absorption, distribution, metabolism, excretion and toxicity (ADMET) analysis of the potential phytocompounds and repurposing drugs against three targets of SARS-CoV-2 proteins (RNA dependent RNA polymerase, RdRp, Endoribonclease, S-protein of ACE2-RBD). The docking data illustrated Arachidonic acid, Rutin, Quercetin, and Curcumin were highly bound with coronavirus polyprotein replicase and Ebolavirus envelope protein. Furthermore, anti- Ebolavirus molecule Remedesivir, anti-HIV molecule Chloroquine, and Darunavir were repurposed with coronavirus polyprotein replicase as well as Ebolavirus envelope protein. The strongest binding interaction of each targets are Rutin with RdRp, Endoribonclease with Amentoflavone, and ACE2-RBD with Epigallocatechin gallate. Taken altogether, these results shed a light on that phytocompounds have a therapeutic potential for the treatment of anti-SARS-CoV-2 may base on multi-target effects or cocktail formulation for blocking viral infection through invasion/activation, transcription/reproduction, and posttranslational cleavage to battle COVID-19 pandemic. [Display omitted] • In silico discovers the potential phytocompounds combating high-infection virus. • 3D mapping exerts the specific banding site of SARS-CoV-2 with potential anti-virus drugs • Phytomedicines interrupt and hinder virus-entry, viral replication and immune evasion of COVID-19. [ABSTRACT FROM AUTHOR]

Summary: To address the functions of SigN (SCO4034) in Streptomyces coelicolor, we constructed a sigN null mutant M145Z, which showed a defect in sporulation. The differential proteomic profiles of wild-type S. coelicolors M145 and M145Z were demonstrated by two-dimensional polyacrylamide gel electrophoresis (2D PAGE), which identified 24 different spots that were up- or down-regulated due to sigN disruption. Among them, 22 proteins were identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). The up-regulated proteins were involved in energy metabolism, stress responses, ATP binding, ppGpp stringent stress response and transcriptional anti-termination, etc. The down-regulated proteins were related to antibiotic synthesis and differentiation. The results gave a new insight into the regulatory mechanism of SigN in S. coelicolor. Furthermore, deletion of sigN caused growth retardation under all stress conditions examined including heat, cold, acid, oxidation, salt and ethanol. These results indicated that SigN was involved in morphological development, secondary metabolism and stress responses in S. coelicolor. [Copyright &y& Elsevier]