Significance: Recent spread of SARS-CoV-2 has sparked significant health concerns of emerging infectious viruses. Drug repurposing is a tangible strategy for developing antiviral agents within a short period. In general, drug repurposing starts with virtual screening of approved drugs employing docking simulations. However, the actual hit rate is low, and most of the predicted compounds are false positives. To tackle the challenges, we report advanced virtual screening with pre- and postdocking pharmacophore filtering of 6,218 drugs for COVID-19. Notably, 7 out of 38 compounds showed efficacies in inhibiting SARS-CoV-2 in Vero cells. Three of these were also found to inhibit SARS-CoV-2 in human Calu-3 cells. Furthermore, three drug combinations showed strong synergistic effects in SARS-CoV-2 inhibition at their clinically achievable concentrations.

Bio-based production of many chemicals is not yet possible due to the unknown biosynthetic pathways. Here, we report a strategy combining retrobiosynthesis and precursor selection step to design biosynthetic pathways for multiple short-chain primary amines (SCPAs) that have a wide range of applications in chemical industries. Using direct precursors of 15 target SCPAs determined by the above strategy,Streptomyces viridifaciens vlmDencoding valine decarboxylase is examined as a proof-of-concept promiscuous enzyme both in vitro and in vivo for generating SCPAs from their precursors.Escherichia coliexpressing the heterologousvlmDproduces 10 SCPAs by feeding their direct precursors. Furthermore, metabolically engineeredE. colistrains are developed to produce representative SCPAs from glucose, including the one producing 10.67 g L⁻¹ofiso-butylamine by fed-batch culture. This study presents the strategy of systematically designing biosynthetic pathways for the production of a group of related chemicals as demonstrated by multiple SCPAs as examples.