Mycobacterium smegmatis (M.sm) is frequently used as an alternative model organism in Mycobacterium tuberculosis (M.tb) studies. While containing high sequence homology with M.tb, it is considered non-pathogenic in humans. As such it has been used to study M.tb and other infections in vivo and more recently been explored for potential therapeutic applications. A body of previous research has highlighted the potential of using genetically modified M.sm displaying rapid growth and unique immunostimulatory characteristics as an effective vaccine vector. Novel systems biology techniques can further serve to optimize these delivery constructs. In this article, we review recent advancements in vaccinomics tools that support the efficacy of a M.sm-based vaccine vector. Moreover, the integration of systems biology and molecular omics techniques in these pioneering studies heralds a potential accelerated pipeline for the development of next-generation recombinant vaccines against rapidly developing diseases.

Nitrogen metabolism is an important physiological process that affects the survival and virulence of Mycobacterium tuberculosis. M. tuberculosis’s utilization of nitrogen in the environment and its adaptation to the harsh environment of acid and low oxygen in macrophages are closely related to nitrogen metabolism. In addition, the dormancy state and drug resistance of M. tuberculosis are closely related to nitrogen metabolism. Although nitrogen metabolism is so important, limited research was performed on nitrogen metabolism as compared with carbon metabolism. M. tuberculosis can use a variety of inorganic or organic nitrogen sources, including ammonium salts, nitrate, glutamine, asparagine, etc. In these metabolic pathways, some enzymes encoded by key genes, such as GlnA1, AnsP2, etc, play important regulatory roles in the pathogenesis of TB. Although various small molecule inhibitors and drugs have been developed for different nitrogen metabolism processes, however, long-term validation is needed before their practical application. Most importantly, with the emergence of multidrug-resistant strains, eradication, and control of M. tuberculosis will still be very challenging.

Porcine epidemic diarrhea virus (PEDV) is a swine coronavirus that is highly infectious and prone to variation. Vaccines derived from traditional PEDV strains provide less protection against PEDV-variant strains. Furthermore; there is a complex diversity of sequences among various PEDV-variant strains. Therefore; there is an urgent need to develop alternative antiviral strategies to defend against PEDV. Molnupiravir is a nucleotide analogue that could replace natural nucleosides to restrain viral RNA replication. Our study provided evidence for the dose-dependent inhibition of PEDV replication by molnupiravir in Vero cells. Molnupiravir also exhibited a strong inhibitory effect on viral RNA and protein production. Our results demonstrated that molnupiravir inhibits PEDV RNA-dependent RNA polymerase (RdRp) activity and induces a high frequency of mutations in the PEDV genome. Further studies revealed that molnupiravir can reverse changes in the transcriptome caused by viral infection. In conclusion, our results indicated that molnupiravir has the potential to be an effective treatment for PEDV infection.

Porcine Epidemic Diarrhea Virus (PEDV) is a highly contagious and pathogenic virus that causes symptoms such as diarrhea, vomiting, weight loss, and even death in piglets. Due to its high transmission rate, PEDV has resulted in significant global losses. Although some vaccines have been developed and utilized to prevent PEDV, their effectiveness is limited due to the virus's mutations. Therefore, it is imperative to investigate new strategies to combat PEDV. Remdesivir, a classic antiviral drug for coronaviruses, has been proven in our experiment to effectively suppress PEDV replication in Vero and LLC-PK1 cells. Additionally, the cell experiment demonstrated its direct inhibition of PEDV RNA-dependent RNA polymerase (RdRp) enzyme activity. Molecular docking simulations were employed to predict the binding site of remdesivir and PEDV RdRp. Moreover, we observed that remdesivir does not impact the production of inflammatory factors and exhibits antagonistic effects with exogenous nucleosides. Furthermore, we conducted RNA-Seq analysis to investigate the global changes in transcriptome of infected cells treated with remdesivir. Overall, our findings indicate that remdesivir holds promise as a potential candidate for the treatment of PEDV infection.