gene polymorphism common in East Asians confers decreased COVID-19 susceptibility.

COVID-19 has a wide range of clinical presentations, and the susceptibility to SARS-CoV-2 infection and the mortality rate also vary by region and ethnicity. Here, we found that rs12329760 in the gene, a missense variant common in East Asian populations, contributes to protection against SARS-CoV-2 infection. TMPRSS2 is a protease responsible for SARS-CoV-2 entry and syncytium formation.

3CL Protease Inhibitors with an Electrophilic Arylketone Moiety as Anti-SARS-CoV-2 Agents.

The novel coronavirus, SARS-CoV-2, has been identified as the causative agent for the current coronavirus disease (COVID-19) pandemic. 3CL protease (3CL) plays a pivotal role in the processing of viral polyproteins. We report peptidomimetic compounds with a unique benzothiazolyl ketone as a warhead group, which display potent activity against SARS-CoV-2 3CL.

Potent mouse monoclonal antibodies that block SARS-CoV-2 infection.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has developed into a global pandemic since its first outbreak in the winter of 2019. An extensive investigation of SARS-CoV-2 is critical for disease control. Various recombinant monoclonal antibodies of human origin that neutralize SARS-CoV-2 infection have been isolated from convalescent patients and will be applied as therapies and prophylaxis.

Influenza restriction factor MxA functions as inflammasome sensor in the respiratory epithelium.

The respiratory epithelium is exposed to the environment and initiates inflammatory responses to exclude pathogens. Influenza A virus (IAV) infection triggers inflammatory responses in the respiratory mucosa, but the mechanisms of inflammasome activation are poorly understood. We identified MxA as a functional inflammasome sensor in respiratory epithelial cells that recognizes IAV nucleoprotein and triggers the formation of ASC (apoptosis-associated speck-like protein containing a CARD) specks via interaction of its GTPase domain with the PYD domain of ASC.

Inhibition of Influenza Virus Infection by Mycelia Extract Through Its Direct Action and Immunopotentiating Activity.

mycelia (LEM) solid culture extracts contain many bioactive compounds with diverse pharmacological activities such as antitumor, antiviral, and immunopotentiating effects. In this study, we examined the anti-influenza virus activity of LEM and . LEM directly inhibited influenza virus growth at early phases of infection, possibly at the entry process of viral particles to host cells.

Influenza A Virus Infection Triggers Pyroptosis and Apoptosis of Respiratory Epithelial Cells through the Type I Interferon Signaling Pathway in a Mutually Exclusive Manner.

Respiratory epithelial cell death by influenza virus infection is responsible for the induction of inflammatory responses, but the exact cell death mechanism is not understood. Here we showed that influenza virus infection induces apoptosis and pyroptosis in normal or precancerous human bronchial epithelial cells. Apoptosis was induced only in malignant tumor cells infected with influenza virus.

Identification of new SUMO activating enzyme 1 inhibitors using virtual screening and scaffold hopping.

Sumoylation involves the enzymatic conjugation of small ubiquitin-like modifier (SUMO) protein to their substrate proteins. Sumoylation is not only crucial for maintaining normal cellular physiology but also implicated in the development of several diseases including cancer. SUMO E1, the first protein in sumoylation pathway is of particular significance due to its confirmed role in tumorogenesis.

Influenza Virus Induces Cholesterol-Enriched Endocytic Recycling Compartments for Budozone Formation via Cell Cycle-Independent Centrosome Maturation.

Influenza virus particles are assembled at the plasma membrane in concert with incorporation of the virus genome, but the details of its spatio-temporal regulation are not understood. Here we showed that influenza virus infection induces the assembly of pericentrosomal endocytic recycling compartment (ERC) through the activation of Rab11a GTPase and cell cycle-independent maturation of centrosome by YB-1, a multifunctional protein that is involved in mitotic division, RNA metabolism and tumorigenesis. YB-1 is recruited to the centrosome in infected cells and is required for anchoring microtubules to the centrosome.

Identification of sumoylation inhibitors targeting a predicted pocket in Ubc9.

Sumoylation is a post-translational modification that plays an important role in a wide range of cellular processes. Among the proteins involved in the sumoylation pathway, Ubc9 is the sole E2-conjugating enzyme required for sumoylation and plays a central role by interacting with almost all of the partners required for sumoylation. Ubc9 has been implicated in a variety of human malignancies.

Assay methods for small ubiquitin-like modifier (SUMO)-SUMO-interacting motif (SIM) interactions in vivo and in vitro using a split-luciferase complementation system.

SUMOylation is a posttranslational process that attaches a small ubiquitin-like modifier (SUMO) to its target proteins covalently. SUMOylation controls multiple cellular processes through the recognition of SUMO by a SUMO-interacting motif (SIM). In this study, we developed assay systems for detecting noncovalent interactions between SUMO and SIM in cells using split-luciferase complementation.

Spectomycin B1 as a novel SUMOylation inhibitor that directly binds to SUMO E2.

Conjugation of small ubiquitin-like modifier (SUMO) to protein (SUMOylation) regulates multiple biological systems by changing the functions and fates of a large number of proteins. Consequently, abnormalities in SUMOylation have been linked to multiple diseases, including breast cancer. Using an in situ cell-based screening system, we have identified spectomycin B1 and related natural products as novel SUMOylation inhibitors.

Identification of quinazolinyloxy biaryl urea as a new class of SUMO activating enzyme 1 inhibitors.

SUMO activating enzyme 1 (SUMO E1) is the first enzyme in sumoylation pathway and an important cancer drug target. However, only a few inhibitors were reported up to now that includes three natural products, semi-synthetic protein inhibitors and one AMP mimic. Here, we report the identification of quinazolinyloxy biaryl urea as a new class of SUMO E1 inhibitors.

Identification of sumoylation activating enzyme 1 inhibitors by structure-based virtual screening.

SUMO activating enzyme 1 (SUMO E1) is responsible for the activation of SUMO in the first step of the sumoylation cascade. SUMO E1 is linked to many human diseases including cancer, thus making it a potential therapeutic target. There are few reported SUMO E1 inhibitors including several natural products.