Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) entry is mediated by the interaction of the viral spike (S) protein with angiotensin‐converting enzyme 2 (ACE2) on the host cell surface. Although a clinical trial testing soluble ACE2 (sACE2) for COVID‐19 is currently ongoing, our understanding of the delivery of sACE2 via small extracellular vesicles (sEVs) is still rudimentary. With excellent biocompatibility allowing for the effective delivery of molecular cargos, sEVs are broadly studied as nanoscale protein carriers. In order to exploit the potential of sEVs, we design truncated CD9 scaffolds to display sACE2 on the sEV surface as a decoy receptor for the S protein of SARS‐CoV‐2. Moreover, to enhance the sACE2‐S binding interaction, we employ sACE2 variants. sACE2‐loaded sEVs exhibit typical sEVs characteristics and bind to the S protein. Furthermore, engineered sEVs inhibit the entry of wild‐type (WT), the globally dominant D614G variant, Beta (K417N‐E484K‐N501Y) variant, and Delta (L452R‐T478K‐D614G) variant SARS‐CoV‐2 pseudovirus, and protect against authentic SARS‐CoV‐2 and Delta variant infection. Of note, sACE2 variants harbouring sEVs show superior antiviral efficacy than WT sACE2 loaded sEVs. Therapeutic efficacy of the engineered sEVs against SARS‐CoV‐2 challenge was confirmed using K18‐hACE2 mice. The current findings provide opportunities for the development of new sEVs‐based antiviral therapeutics.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused corona virus disease 2019 (COVID-19) pandemic and led to mass casualty. Even though much effort has been put into development of vaccine and treatment methods to combat COVID-19, no safe and efficient cure has been discovered. Drug repurposing or drug repositioning which is a process of investigating pre-existing drug candidates for novel applications outside their original medical indication can speed up the drug development process. Raloxifene is a selective estrogen receptor modulator (SERM) that has been approved by FDA in 1997 for treatment and prevention of postmenopausal osteoporosis and cancer. Recently, raloxifene demonstrates efficacy in treating viral infections by Ebola, influenza A, and hepatitis C viruses and shows potential for drug repurposing for the treatment of SARS-CoV-2 infection. This review will provide an overview of raloxifene’s mechanism of action as a SERM and present proposed mechanisms of action in treatment of viral infections.

The ability of Staphylococcus aureus to adapt and thrive in diverse host niches adds to the challenge in combating this ubiquitous pathogen. While extensive research has been pursued on the adaptive mechanisms of methicillin-resistant S. aureus (MRSA) in various infection models, a comprehensive analysis of its fitness across different host niches is lacking. In this study, we employ transposon sequencing to analyze the adaptive strategies of MRSA in various infection niches. Our analysis encompasses a cell model that mimics an intracellular niche, human blood, which represents a major extracellular environment as well as a major intermediary route encountered by bacteria during systemic infection, and a male murine sepsis model that recapitulates intra-organ environments. Our findings reveal substantial differences in the genetic determinants essential for bacterial survival in intracellular and blood environments. Moreover, we show that each organ imposes unique growth constraints, thus fostering heterogeneity within the mutant population that can enter and survive in each organ of the mouse. By comparing genes important for survival across all examined host environments, we identify 27 core genes that represent potential therapeutic targets for treating S. aureus infections. Additionally, our findings aid in understanding how bacteria adapt to diverse host environments.

Synthetic biology approaches offer potential for large-scale and sustainable production of natural products with bioactive potency, including ginsenosides, providing a means to produce novel compounds with enhanced therapeutic properties. Ginseng, known for its non-toxic and potent qualities in traditional medicine, has been used for various medical needs. Ginseng has shown promise for its antioxidant and neuroprotective properties, and it has been used as a potential agent to boost immunity against various infections when used together with other drugs and vaccines. Given the increasing demand for ginsenosides and the challenges associated with traditional extraction methods, synthetic biology holds promise in the development of therapeutics. In this review, we discuss recent developments in microorganism producer engineering and ginsenoside production in microorganisms using synthetic biology approaches.

Mycobacterium aviumcomplex (MAC) is the main causative agent of infectious diseases in humans among nontuberculous mycobacteria (NTM) that are ubiquitous organisms found in environmental media such as soil as well as in domestic and natural waters. MAC is a primary causative agent of NTM-lung disease that threaten immunocompromised or structural lung disease patients. The incidence and the prevalence ofM. tuberculosisinfection have been reduced, while MAC infections and mortality rates have increased, making it a cause of global health concern. The emergence of drug resistance and the side effects of long-term drug use have led to a poor outcome of treatment regimens against MAC infections. Therefore, the development of host-directed therapy (HDT) has recently gained interest, aiming to accelerate mycobacterial clearance and reversing lung damage by employing the immune system using a novel adjuvant strategy to improve the clinical outcome of MAC infection. Therefore, in this review, we discuss the innate immune responses that contribute to MAC infection focusing on macrophages, chief innate immune cells, and host susceptibility factors in patients. We also discuss potential HDTs that can act on the signaling pathway of macrophages, thereby contributing to antimycobacterial activity as a part of the innate immune response during MAC infection. Furthermore, this review provides new insights into MAC infection control that modulates and enhances macrophage function, promoting host antimicrobial activity in response to potential HDTs and thus presenting a deeper understanding of the interactions between macrophages and MACs during infection.