Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), an epidemic disease characterized by rapid infection and a high death toll. The clinical diagnosis of patients with COVID-19 has risen sharply, especially in Western countries. Globally, an effective treatment for COVID-19 is still limited. Vitamin A (VA) exhibits pharmacological activity in the management of pneumonia. Thus, we reason that VA may potentially serve as an anti-SARS-CoV-2 regimen. In this study, bioinformatics analysis and computation assays using a network pharmacology method were conducted to explore and uncover the therapeutic targets and mechanisms of VA for treating COVID-19. We identified candidate targets, pharmacological functions, and therapeutic pathways of VA against SARS-CoV-2. Bioinformatics findings indicate that the mechanisms of action of VA against SARS-CoV-2 include enrichment of immunoreaction, inhibition of inflammatory reaction, and biological processes related to reactive oxygen species. Furthermore, seven core targets of VA against COVID-19, including MAPK1, IL10, EGFR, ICAM1, MAPK14, CAT, and PRKCB were identified. With this bioinformatics-based report, we reveal, for the first time, the anti-SARS-CoV-2 functions and mechanisms of VA and suggest that VA may act as a potent treatment option for COVID-19, a deadly global epidemic.

Background: Deconjugation of ubiquitin and/or ubiquitin-like modified protein substrates is essential to modulate protein-protein interactions and, thus, signaling processes in cells. Although deubiquitylating (deubiquitinating) enzymes (DUBs) play a key role in this process, however, their function and regulation remain insufficiently understood. The "loss-of-function" phenotype studies can provide important information to elucidate the gene function, and zebrafish is an excellent model for this goal. Results: From an in silico genome-wide search, we found more than 90 putative DUBs encoded in the zebrafish genome belonging to six different subclasses. Out of them, 85 from five classical subclasses have been tested with morpholino (MO) knockdown experiments and 57 of them were found to be important in early development of zebrafish. These DUB morphants resulted in a complex and pleiotropic phenotype that, regardless of gene target, always affected the notochord. Based on the huC neuronal marker expression, we grouped them into five sets (groups I to V). Group I DUBs (otud7b, uchl3 and bap1) appear to be involved in the Notch signaling pathway based on the neuronal hyperplasia, while group IV DUBs (otud4, usp5, usp15 and usp25) play a critical role in dorsoventral patterning through the BMP pathway. Conclusion: We have identified an exhaustive list of genes in the zebrafish genome belonging to the five established classes of DUBs. Additionally, we performed the corresponding MO knockdown experiments in zebrafish as well as functional studies for a subset of the predicted DUB genes. The screen results in this work will stimulate functional follow-up studies of potential DUB genes using the zebrafish model system.