Applications of Artificial Intelligence in Biotech Drug Discovery and Product Development.

Artificial intelligence (AI) is revolutionizing biotechnology by transforming the landscape of therapeutic development. Traditional drug discovery faces persistent challenges, including high attrition rates, billion-dollar costs, and timelines exceeding a decade. Recent advances in AI-particularly generative models such as generative adversarial networks, variational autoencoders, and diffusion models-have introduced data-driven, iterative workflows that dramatically accelerate and enhance pharmaceutical R&D.

Desmocollin 2 is a dominant entry receptor for Epstein-Barr virus infection of epithelial cells.

Epstein-Barr virus (EBV) can infect B cells and epithelial cells, and cause lymphomas and various epithelial malignancies. During epithelial cell infection, EBV employs a complex combination of viral glycoproteins and host receptors. However, the exact mechanism and whether a dominant receptor exists remain unclear.

Human herpesvirus 6B glycoprotein B postfusion structure, vulnerability mapping, and receptor recognition.

Human herpesvirus 6B (HHV-6B), a β-herpesvirus that significantly threatens immunocompromised individuals, currently lacks targeted antiviral therapies or vaccines. Glycoprotein B (gB), the primary mediator of membrane fusion during viral entry, is a key target for neutralizing antibody (nAb) and vaccine development. In this study, we determined a 2.

The PLEKHA1-TACC2 fusion gene drives tumorigenesis via vascular mimicry formation in esophageal squamous-cell carcinoma.

Despite advancements of diagnosis and multimodality therapies in esophageal squamous-cell carcinoma (ESCC), the survival is still unsatisfactory. Therefore, it is urgent to identify novel targets for efficient therapeutic strategies. Herein, we identify a fusion gene between PLEKHA1 and TACC2 generated by chromosomal rearrangement by performing RNA sequencing from ESCC tissues.

OASL enhances mRNA translation and reprograms lipid metabolism to promote cancer progression.

Type I interferons (IFN-Is) are central coordinators of tumor-immune system interactions. Accumulating evidence suggests that persistent IFN-Is and a subset of IFN-stimulated genes (ISGs) might promote tumor development, but the regulation of mRNA translation and lipid metabolism during this process remains unknown. Here, we report that oligoadenylate synthetase-like (OASL) is a key ISG in mediating the pro-tumor effects of IFN-Is.

Interferon-responsive HEVs drive tumor tertiary lymphoid structure formation and predict immunotherapy response in nasopharyngeal carcinoma.

The outcome of immune checkpoint blockade (ICB) therapy largely hinges on the antitumor immunity of tertiary lymphoid structures (TLSs), but drivers of tumor TLS formation remain exclusive. By integrating spatial transcriptomics and a pan-cancer single-cell atlas, we reveal the characteristics of TLSs in nasopharyngeal carcinoma (NPC) and identify a subset of interferon-responsive high endothelial venules (IFN-HEVs) that links to the emergence of tumor-specific chemokines, especially CXCL9. Functionally, CXCL9-secreting IFN-HEVs are associated with the recruitment of CXCR3CD4 T cells into TLSs.

R9AP is a common receptor for EBV infection in epithelial cells and B cells.

Epstein-Barr virus (EBV) persistently infects more than 90% of the human population, causing infectious mononucleosis, susceptibility to autoimmune diseases and multiple malignancies of epithelial or B cell-origin. EBV infects epithelial cells and B cells through interaction between viral glycoproteins and different host receptors, but it has remained unknown whether a common receptor mediates infection of its two major host cell targets. Here, we establish R9AP as a crucial EBV receptor for entry into epithelial and B cells.

Immunosequencing identifies signatures of T cell responses for early detection of nasopharyngeal carcinoma.

To identify nasopharyngeal carcinoma (NPC)-relevant T cell receptors (TCRs), we profile the repertoires of peripheral blood TCRβ chains from 228 NPC patients, 241 at-risk controls positive for serum Epstein-Barr virus (EBV) VCA-IgA antibody, and 251 seronegative controls. We develop a TCR-based signature (T-score) based on 208 NPC-enriched CDR3β sequences, which accurately diagnoses NPC in both the original and independent validation cohorts. Notably, a higher T-score, associated with a shorter time interval to NPC diagnosis, effectively identifies early-stage NPC among EBV-seropositive at-risk individuals prior to clinical diagnosis.

Structure and Antigenicity of Kaposi's Sarcoma-Associated Herpesvirus Glycoprotein B.

Kaposi's sarcoma-associated herpesvirus (KSHV), a member of the human γ-herpesviruses family, exhibits extensive cellular tropism and is associated with Kaposi's sarcoma and various B-cell malignancies. Despite its clinical significance, no effective prophylactic vaccines or specific therapeutics are currently available to prevent or treat KSHV infection. Similar to other herpesviruses, KSHV depends on the envelope glycoprotein B (gB) for host receptor recognition and membrane fusion initiation, making gB a prime target for antiviral antibody or vaccine development.

A Chimeric Virus-Like Particle Vaccine Presenting an Immunodominant Epitope of gB Elicited Potent Neutralizing Antibodies against EBV Infection and .

Epstein-Barr Virus (EBV) as the first characterized tumorigenic virus in humans causes heavy disease burdens. An effective vaccine is urgently needed to block EBV infection. Glycoprotein B (gB) is the essential fusogen for EBV infection of all susceptible cell types.

Inactivation of TACC2 epigenetically represses CDKN1A and confers sensitivity to CDK inhibitors.

Background: The genomic landscape of esophageal squamous cell carcinoma (ESCC) has been characterized extensively, but there remains a significant need for actionable targets and effective therapies.

Methods: Here, we perform integrative analysis of genome-wide loss of heterozygosity and expression to identify potential tumor suppressor genes. The functions and mechanisms of one of the candidates, TACC2, are then explored both in vitro and in vivo, leading to the proposal of a therapeutic strategy based on the concept of synthetic lethality.

Structural basis of Epstein-Barr virus gp350 receptor recognition and neutralization.

Epstein-Barr virus (EBV) is an oncogenic virus associated with multiple lymphoid malignancies and autoimmune diseases. During infection in B cells, EBV uses its major glycoprotein gp350 to recognize the host receptor CR2, initiating viral attachment, a process that has lacked direct structural evidence for decades. In this study, we resolved the structure of the gp350-CR2 complex, elucidated their key interactions, and determined the site-specific N-glycosylation map of gp350.

Research landmarks on the 60th anniversary of Epstein-Barr virus.

Epstein-Barr virus (EBV), the first human oncovirus discovered in 1964, has become a focal point in virology, immunology, and oncology because of its unique biological characteristics and significant role in human diseases. As we commemorate the 60th anniversary of EBV's discovery, it is an opportune moment to reflect on the major advancements in our understanding of this complex virus. In this review, we highlight key milestones in EBV research, including its virion structure and life cycle, interactions with the host immune system, association with EBV-associated diseases, and targeted intervention strategies.

Design and characterization of defined alpha-helix mini-proteins with intrinsic cell permeability.

Proteins with intrinsic cell permeability that can access intracellular targets represent a promising strategy for novel drug development; however, a general design principle is still lacking. Here, we established a library of 46,678 de novo-designed mini-proteins and performed cell permeability screening via phage display. Analyses revealed a characteristic neighboring distribution of positive charges across helices among enriched mini-proteins of CPP7, CPP11, CPP55, CPP109 and CPP112.

Primary and Orthotopic Murine Models of Nasopharyngeal Carcinoma Reveal Molecular Mechanisms Underlying its Malignant Progression.

Nasopharyngeal carcinoma (NPC), a squamous cell carcinoma originating in the nasopharynx, is a leading malignancy in south China and other south and east Asia areas. It is frequently associated with Epstein-Barr virus (EBV) infection, while there are also some NPC patients without EBV infection. Here, it is shown that the EBV+ (EBV positive) and EBV- (EBV negative) NPCs contain both shared and distinct genetic abnormalities, among the latter are increased mutations in TP53.

A pan-KRAS degrader for the treatment of KRAS-mutant cancers.

KRAS mutations are highly prevalent in a wide range of lethal cancers, and these mutant forms of KRAS play a crucial role in driving cancer progression and conferring resistance to treatment. While there have been advancements in the development of small molecules to target specific KRAS mutants, the presence of undruggable mutants and the emergence of secondary mutations continue to pose challenges in the clinical treatment of KRAS-mutant cancers. In this study, we developed a novel molecular tool called tumor-targeting KRAS degrader (TKD) that effectively targets a wide range of KRAS mutants.

Potent human monoclonal antibodies targeting Epstein-Barr virus gp42 reveal vulnerable sites for virus infection.

Epstein-Barr virus (EBV) is linked to various malignancies and autoimmune diseases, posing a significant global health challenge due to the lack of specific treatments or vaccines. Despite its crucial role in EBV infection in B cells, the mechanisms of the glycoprotein gp42 remain elusive. In this study, we construct an antibody phage library from 100 EBV-positive individuals, leading to the identification of two human monoclonal antibodies, 2B7 and 2C1.