[Targets and mechanisms of neutralizing monoclonal antibodies against Dengue virus].

Dengue fever is a mosquito-borne disease prevalent in tropical and subtropical regions, with its prevalence expanding due to increased global travel. The dengue virus, the causative agent of dengue fever, often co-circulates in the form of four distinct serotypes. Cross-reactive antibodies generated during a primary infection pose a significant risk during secondary infections with different serotypes, and fully protective vaccines and antiviral drugs are yet to be developed.

mRNA vaccines: A promising platform for safer, more effective next-generation Orthopoxvirus immunization.

In recent work, Mucker et al. demonstrated that mRNA-1769 outperforms modified vaccinia Ankara (MVA), which has been deployed against recent mpox virus (MPXV) outbreaks, in reducing clinical symptoms and controlling viral replication, highlighting its potential as a scalable, safe, and effective next-generation platform for orthopoxvirus vaccination.

Chest CT features and risk factors for patients with Omicron variant pneumonia: a multicenter retrospective clinical study.

Introduction: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron variant infection has become widespread in China as a result of the alterations in epidemic control and prevention policies. We identified the clinical characteristics and lung computed tomography (CT) imaging characteristics of patients infected during the early stage of the Omicron BA.5 wave in Shanghai to provide a guide to the diagnosis, treatment, and prognosis of infection.

Mpox multi-antigen mRNA vaccine candidates by a simplified manufacturing strategy afford efficient protection against lethal orthopoxvirus challenge.

Current unprecedented mpox outbreaks in non-endemic regions represent a global public health concern. Although two live-attenuated vaccinia virus (VACV)-based vaccines have been urgently approved for people at high risk for mpox, a safer and more effective vaccine that can be available for the general public is desperately needed. By utilizing a simplified manufacturing strategy of mixing DNA plasmids before transcription, we developed two multi-antigen mRNA vaccine candidates, which encode four (M1, A29, B6, A35, termed as Rmix4) or six (M1, H3, A29, E8, B6, A35, termed as Rmix6) mpox virus antigens.

A combination vaccine against SARS-CoV-2 and H1N1 influenza based on receptor binding domain trimerized by six-helix bundle fusion core.

Background: Increasing severe morbidity and mortality by simultaneous or sequential infections with SARS-CoV-2 and influenza A viruses (IAV), especially in the elderly and obese patients, highlight the urgency of developing a combination vaccine against COVID-19 and influenza.

Methods: Self-assembling SARS-CoV-2 RBD-trimer and Influenza H1N1 HA1-trimer antigens were constructed, upon the stable fusion core in post-fusion conformation. Immunogenicity of SARS-CoV-2 RBD-trimer vaccine and H1N1 HA1-trimer antigens candidates were evaluated in mice.

A neutralizing-protective supersite of human monoclonal antibodies for yellow fever virus.

The yellow fever virus (YFV) is a life-threatening human pathogen. Owing to the lack of available therapeutics, non-vaccinated individuals are at risk. Here, we isolated eight human monoclonal antibodies that neutralize YFV infection.

Anti-diabetic effects of linarin from via AMPK activation.

Objective: The purpose of this study is to investigate the anti-diabetic effects of linarin, a flavonoid extracted from (CIF), and its potential mechanisms.

Methods: The effects of linarin on cell viability and glucose consumption in HepG2 cells were measured. Meanwhile, monosodium glutamate (MSG) mouse model was constructed to monitor the changes of insulin tolerance, glucose tolerance, triglyceride and cholesterol.

Structure-based neutralizing mechanisms for SARS-CoV-2 antibodies.

The devastating economic and public health consequences caused by the COVID-19 pandemic have prompted outstanding efforts from the scientific community and pharmaceutical companies to develop antibody-based therapeutics against SARS-CoV-2. Those efforts are encouraging and fruitful. An unprecedentedly large number of monoclonal antibodies (mAbs) targeting a large spectrum of epitopes on the spike protein has been developed in the last two years.

[Clinical progress of neutralizing antibodies against SARS-CoV-2].

Since the palivizumab for respiratory syncytial virus was approved in 1998, therapeutic antibodies against infectious diseases have been widely used in clinical treatment. Since the outbreak of COVID-19, plenty of neutralizing antibodies were developed and transferred into clinical trials, holding enormous promise for the treatment of COVID-19 under the context of emergency use authorization. This review summarizes the clinical progress of these drugs, in order to provide a reference for the research and development of neutralizing antibody drugs for the future.

Efficacy and Safety of the RBD-Dimer-Based Covid-19 Vaccine ZF2001 in Adults.

Background: The ZF2001 vaccine, which contains a dimeric form of the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 and aluminum hydroxide as an adjuvant, was shown to be safe, with an acceptable side-effect profile, and immunogenic in adults in phase 1 and 2 clinical trials.

Methods: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial to investigate the efficacy and confirm the safety of ZF2001. The trial was performed at 31 clinical centers across Uzbekistan, Indonesia, Pakistan, and Ecuador; an additional center in China was included in the safety analysis only.

A tandem-repeat dimeric RBD protein-based covid-19 vaccine zf2001 protects mice and nonhuman primates.

Safe, efficacious, and deployable vaccines are urgently needed to control COVID-19 in the large-scale vaccination campaigns. We report here the preclinical studies of an approved protein subunit vaccine against COVID-19, ZF2001, which contains tandem-repeat dimeric receptor-binding domain (RBD) protein with alum-based adjuvant. We assessed vaccine immunogenicity and efficacy in both mice and non-human primates (NHPs).

Novel (Z)/(E)-1,2,4-triazole derivatives containing oxime ether moiety as potential ergosterol biosynthesis inhibitors: design, preparation, antifungal evaluation, and molecular docking.

Inspired by the highly effective and broad-spectrum antifungal activity of ergosterol biosynthesis inhibitions, a series of novel 1,2,4-triazole derivatives containing oxime ether moiety were constructed for screening the bioactivity against phytopathogenic fungi. The (Z)- and (E)-isomers of target compounds were successfully separated and identified by the spectroscopy and single crystal X-ray diffraction analyses. The bioassay results showed that the (Z)-isomers of target compounds possessed higher antifungal activity than the (E)-isomers.

Etesevimab in combination with JS026 neutralizing SARS-CoV-2 and its variants.

The neutralizing antibody is a potential therapeutic for the ongoing COVID-19 pandemic. As an antiviral agent, numerous mAbs recognize the epitopes that overlap with ACE2-binding sites in the SARS-CoV-2-RBD. Some studies have shown that residual changes on the spike protein can significantly decrease the efficiency of neutralizing antibodies.

Macrophage deletion of Noc4l triggers endosomal TLR4/TRIF signal and leads to insulin resistance.

In obesity, macrophages drive a low-grade systemic inflammation (LSI) and insulin resistance (IR). The ribosome biosynthesis protein NOC4 (NOC4) mediates 40 S ribosomal subunits synthesis in yeast. Hereby, we reported an unexpected location and function of NOC4L, which was preferentially expressed in human and mouse macrophages.

Molecular insights into receptor binding of recent emerging SARS-CoV-2 variants.

Multiple SARS-CoV-2 variants of concern (VOCs) have been emerging and some have been linked to an increase in case numbers globally. However, there is yet a lack of understanding of the molecular basis for the interactions between the human ACE2 (hACE2) receptor and these VOCs. Here we examined several VOCs including Alpha, Beta, and Gamma, and demonstrate that five variants receptor-binding domain (RBD) increased binding affinity for hACE2, and four variants pseudoviruses increased entry into susceptible cells.

A broadly neutralizing humanized ACE2-targeting antibody against SARS-CoV-2 variants.

The successive emergences and accelerating spread of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages and evolved resistance to some ongoing clinical therapeutics increase the risks associated with the coronavirus disease 2019 (COVID-19) pandemic. An urgent intervention for broadly effective therapies to limit the morbidity and mortality of COVID-19 and future transmission events from SARS-related coronaviruses (SARSr-CoVs) is needed. Here, we isolate and humanize an angiotensin-converting enzyme-2 (ACE2)-blocking monoclonal antibody (MAb), named h11B11, which exhibits potent inhibitory activity against SARS-CoV and circulating global SARS-CoV-2 lineages.

Protective Zika vaccines engineered to eliminate enhancement of dengue infection via immunodominance switch.

Antibody-dependent enhancement (ADE) is an important safety concern for vaccine development against dengue virus (DENV) and its antigenically related Zika virus (ZIKV) because vaccine may prime deleterious antibodies to enhance natural infections. Cross-reactive antibodies targeting the conserved fusion loop epitope (FLE) are known as the main sources of ADE. We design ZIKV immunogens engineered to change the FLE conformation but preserve neutralizing epitopes.

Tolerability, Safety, Pharmacokinetics, and Immunogenicity of a Novel SARS-CoV-2 Neutralizing Antibody, Etesevimab, in Chinese Healthy Adults: a Randomized, Double-Blind, Placebo-Controlled, First-in-Human Phase 1 Study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread rapidly worldwide. This study is the first to report the tolerability, safety, pharmacokinetics (PK), and immunogenicity of a recombinant human anti-SARS-CoV-2 monoclonal antibody, etesevimab (CB6, JS016, LY3832479, or LY-CoV016), in healthy adults. This paper describes a randomized, double-blind, placebo-controlled, phase 1 study.

Safety and immunogenicity of a recombinant tandem-repeat dimeric RBD-based protein subunit vaccine (ZF2001) against COVID-19 in adults: two randomised, double-blind, placebo-controlled, phase 1 and 2 trials.

Background: Although several COVID-19 vaccines have been developed so far, they will not be sufficient to meet the global demand. Development of a wider range of vaccines, with different mechanisms of action, could help control the spread of SARS-CoV-2 globally. We developed a protein subunit vaccine against COVID-19 using a dimeric form of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein as the antigen.