With the frequent outbreaks of emerging infectious diseases in recent years, an effective broad-spectrum antiviral drug is becoming an urgent need for global public health. Cholesterol-25-hydroxylase (CH25H) and its enzymatic products 25-hydroxycholesterol (25HC), a well-known oxysterol that regulates lipid metabolism, have been reported to play multiple functions in modulating cholesterol homeostasis, inflammation, and immune responses. CH25H and 25HC were recently identified as exerting broadly antiviral activities, including upon a variety of highly pathogenic viruses such as human immunodeficiency virus (HIV), Ebola virus (EBOV), Nipah virus (NiV), Rift Valley fever virus (RVFV), and Zika virus (ZIKV). The underlying mechanisms for its antiviral activities are being extensively investigated but have not yet been fully clarified. In this study, we summarized the current findings on how CH25H and 25HC play multiple roles to modulate cholesterol metabolism, inflammation, immunity, and antiviral infections. Overall, 25HC should be further studied as a potential therapeutic agent to control emerging infectious diseases in the future.

With the rapid global spread of the Coronavirus Disease 2019 (COVID-19) pandemic, a safe and effective vaccine against human coronaviruses (HCoVs) is believed to be a top priority in the field of public health. Due to the frequent outbreaks of different HCoVs, the development of a pan-HCoVs vaccine is of great value to biomedical science. The antigen design is a key prerequisite for vaccine efficacy, and we therefore developed a novel antigen with broad coverage based on the genetic algorithm of mosaic strategy. The designed antigen has a potentially broad coverage of conserved cytotoxic T lymphocyte (CTL) epitopes to the greatest extent, including the existing epitopes from all reported HCoV sequences (HCoV-NL63, HCoV-229E, HCoV-OC43, HCoV-HKU1, SARS-CoV, MERS-CoV, and SARS-CoV-2). This novel antigen is expected to induce strong CTL responses with broad coverage by targeting conserved epitopes against multiple coronaviruses.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells mainly by the angiotensin converting enzyme 2 (ACE2) receptor, which can recognize the spike (S) protein by its extracellular domain. Previously, recombinant soluble ACE2 (sACE2) has been clinically used as a therapeutic treatment for cardiovascular diseases. Recent data demonstrated that sACE2 can also be exploited as a decoy to effectively inhibit the cell entry of SARS-CoV-2, through blocking SARS-CoV-2 binding to membrane-anchored ACE2. In this study, we summarized the current findings on the optimized sACE2-based strategies as a therapeutic agent, including Fc fusion to prolong the half-life of sACE2, deep mutagenesis to create high-affinity decoys for SARS-CoV-2, or designing the truncated functional fragments to enhance its safety, among others. Considering that COVID-19 patients are often accompanied by manifestations of cardiovascular complications, we think that administration of sACE2 in COVID-19 patients may be a promising therapeutic strategy to simultaneously treat both cardiovascular diseases and SARS-CoV-2 infection. This review would provide insights for the development of novel therapeutic agents against the COVID-19 pandemic.