Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. Antibody resistance dampens neutralizing antibody therapy and threatens current global Coronavirus (COVID-19) vaccine campaigns. In addition to the emergence of resistant SARS-CoV-2 variants, little is known about how SARS-CoV-2 evades antibodies. Here, we report a novel mechanism of extracellular vesicle (EV)-mediated cell-to-cell transmission of SARS-CoV-2, which facilitates SARS-CoV-2 to escape from neutralizing antibodies. These EVs, initially observed in SARS-CoV-2 envelope protein-expressing cells, are secreted by various SARS-CoV-2-infected cells, including Vero E6, Calu-3, and HPAEpiC cells, undergoing infection-induced pyroptosis. Various SARS-CoV-2-infected cells produce similar EVs characterized by extra-large sizes (1.6–9.5 μm in diameter, average diameter > 4.2 μm) much larger than previously reported virus-generated vesicles. Transmission electron microscopy analysis and plaque assay reveal that these SARS-CoV-2-induced EVs contain large amounts of live virus particles. In particular, the vesicle-cloaked SARS-CoV-2 virus is resistant to neutralizing antibodies and able to reinfect naïve cells independent of the reported receptors and cofactors. Consistently, the constructed 3D images show that intact EVs could be taken up by recipient cells directly, supporting vesicle-mediated cell-to-cell transmission of SARS-CoV-2. Our findings reveal a novel mechanism of receptor-independent SARS-CoV-2 infection via cell-to-cell transmission, provide new insights into antibody resistance of SARS-CoV-2 and suggest potential targets for future antiviral therapeutics.

Artificial intelligence has had a profound impact on life sciences. This review discusses the application, challenges, and future development directions of artificial intelligence in various branches of life sciences, including zoology, plant science, microbiology, biochemistry, molecular biology, cell biology, developmental biology, genetics, neuroscience, psychology, pharmacology, clinical medicine, biomaterials, ecology, and environmental science. It elaborates on the important roles of artificial intelligence in aspects such as behavior monitoring, population dynamic prediction, microorganism identification, and disease detection. At the same time, it points out the challenges faced by artificial intelligence in the application of life sciences, such as data quality, black-box problems, and ethical concerns. The future directions are prospected from technological innovation and interdisciplinary cooperation. The integration of Bio-Technologies (BT) and Information-Technologies (IT) will transform the biomedical research into AI for Science and Science for AI paradigm.

Sequencing of biomacromolecules is a crucial cornerstone in life sciences. Glycans, one of the fundamental biomolecules, derive their physiological and pathological functions from their structures. Glycan sequencing faces challenges due to its structural complexity and current detection technology limitations. As a highly sensitive sensor, nanopores can directly convert nucleic acid sequence information into electrical signals, spearheading the revolution of third-generation nucleic acid sequencing technologies. However, their potential for deciphering complex glycans remains untapped. Initial attempts demonstrated the significant sensitivity of nanopores in glycan sensing, which provided the theoretical basis and insights for the realization of nanopore-based glycan sequencing. Here, we present three potential technical routes to employ nanopore technology in glycan sequencing for the first time. The three novel technical routes include: strand sequencing, capturing glycan chains as they translocate through nanopores; sequential hydrolysis sequencing, capturing released monosaccharides one by one; splicing sequencing, mapping signals from hydrolyzed glycan fragments to an oligosaccharide database/library. Designing suitable nanopores, enzymes, and motors, and extracting characteristic signals pose major challenges, potentially aided by artificial intelligence. It would be highly desirable to design an all-in-one high-throughput glycan sequencer instrument by integrating a sample processing unit, nanopore array, and signal acquisition system into a microfluidic device. The nanopore sequencer invention calls for intensive multidisciplinary cooperation including electrochemistry, glycochemistry, engineering, materials, enzymology, etc. Advancing glycan sequencing will promote the development of basic research and facilitate the discovery of glycan-based drugs and disease markers, fostering progress in glycoscience and even life sciences.

Lack of efficiency has been a major problem shared by all currently developed anti-SARS-CoV-2 therapies. Our previous study shows that SARS-CoV-2 structural envelope (2-E) protein forms a type of cation channel, and heterogeneously expression of 2-E channels causes host cell death. In this study we developed a cell-based high throughput screening (HTS) assay and used it to discover inhibitors against 2-E channels. Among 4376 compounds tested, 34 hits with cell protection activity were found. Followed by an anti-viral analysis, 15 compounds which could inhibit SARS-CoV-2 replication were identified. In electrophysiological experiments, three representatives showing inhibitory effect on 2-E channels were chosen for further characterization. Among them, proanthocyanidins directly bound to 2-E channel with binding affinity (K_D) of 22.14 μM in surface plasmon resonance assay. Molecular modeling and docking analysis revealed that proanthocyanidins inserted into the pore of 2-E N-terminal vestibule acting as a channel blocker. Consistently, mutations of Glu 8 and Asn 15, two residues lining the proposed binding pocket, abolished the inhibitory effects of proanthocyanidins. The natural product proanthocyanidins are widely used as cosmetic, suggesting a potential of proanthocyanidins as disinfectant for external use. This study further demonstrates that 2-E channel is an effective antiviral drug target and provides a potential antiviral candidate against SARS-CoV-2.