Search

Since the coronavirus disease outbreak in 2019, several antibody therapeutics have been developed to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Antibody therapeutics are effective in neutralizing the virus and reducing hospitalization in patients with mild and moderate infections. These therapeutics target the spike protein of SARS-CoV-2; however, emerging mutations in this protein reduce their efficiency. In this study, we developed a universal SARS-CoV-2 neutralizing antibody. We generated a humanized monoclonal antibody, MG1141A, against the receptor-binding domain of the spike protein through traditional mouse immunization. We confirmed that MG1141A could effectively neutralize live viruses, with an EC50 of 92 pM, and that it exhibited effective Fc-mediated functions. Additionally, it retained its neutralizing activity against the alpha (UK), beta (South Africa), and gamma (Brazil) variants of SARS-CoV-2. Taken together, our study contributes to the development of a novel antibody therapeutic approach, which can effectively combat emerging SARS-CoV-2 mutations.

An outbreak of nosocomial infections with Middle East respiratory syndrome coronavirus occurred in South Korea in May 2015. Spike glycoprotein genes of virus strains from South Korea were closely related to those of strains from Riyadh, Saudi Arabia. However, virus strains from South Korea showed strain-specific variations.

In May 2015, Middle East respiratory syndrome coronavirus infection was laboratory confirmed in South Korea. Patients were a man who had visited the Middle East, his wife, and a man who shared a hospital room with the index patient. Rapid laboratory confirmation will facilitate subsequent prevention and control for imported cases.

Japanese encephalitis (JE) is major emerging neurologic disease caused by JE virus. To date, the impact of TLR molecules on JE progression has not been addressed. Here, we determined whether each TLR modulates JE, using several TLR-deficient mouse strains (TLR2, TLR3, TLR4, TLR7, TLR9). Surprisingly, among the tested TLR-deficient mice there were contrasting results in TLR3(-/-) and TLR4(-/-) mice, i.e. TLR3(-/-) mice were highly susceptible to JE, whereas TLR4(-/-) mice showed enhanced resistance to JE. TLR3 ablation induced severe CNS inflammation characterized by early infiltration of inflammatory CD11b(+)Ly-6Chigh monocytes along with profoundly increased viral burden, proinflammatory cytokine/chemokine expression as well as BBB permeability. In contrast, TLR4(-/-) mice showed mild CNS inflammation manifested by reduced viral burden, leukocyte infiltration and proinflammatory cytokine expression. Interestingly, TLR4 ablation provided potent in vivo systemic type I IFN innate response, as well as ex vivo type I IFN production associated with strong induction of antiviral PRRs (RIG-I, MDA5), transcription factors (IRF-3, IRF-7), and IFN-dependent (PKR, Oas1, Mx) and independent ISGs (ISG49, ISG54, ISG56) by alternative activation of IRF3 and NF-κB in myeloid-derived DCs and macrophages, as compared to TLR3(-/-) myeloid-derived cells which were more permissive to viral replication through impaired type I IFN innate response. TLR4 ablation also appeared to mount an enhanced type I IFN innate and humoral, CD4(+) and CD8(+) T cell responses, which were mediated by altered immune cell populations (increased number of plasmacytoid DCs and NK cells, reduced CD11b(+)Ly-6C(high) monocytes) and CD4(+)Foxp3(+) Treg number in lymphoid tissue. Thus, potent type I IFN innate and adaptive immune responses in the absence of TLR4 were closely coupled with reduced JE lethality. Collectively, these results suggest that a balanced triggering of TLR signal array by viral components during JE progression could be responsible for determining disease outcome through regulating negative and positive factors.

The shortage of narrow band gap polymer acceptors with high electron mobility is the major bottleneck for developing efficient all‐polymer solar cells (all‐PSCs). Herein, we synthesize a distannylated electron‐deficient biselenophene imide monomer (BSeI‐Tin) with high purity/reactivity, affording an excellent chance to access acceptor–acceptor (A–A) type polymer acceptors. Copolymerizing BSeI‐Tin with dibrominated monomer Y5‐Br, the resulting A–A polymer PY5‐BSeI shows a higher molecular weight, narrower band gap, deeper‐lying frontier molecular orbital levels and larger electron mobility than the donor–acceptor type counterpart PY5‐BSe. Consequently, the PY5‐BSeI‐based all‐PSCs deliver a remarkable efficiency of 17.77 % with a high short‐circuit current of 24.93 mA cm−2 and fill factor of 75.83 %. This efficiency is much higher than that (10.70 %) of the PY5‐BSe‐based devices. Our study demonstrates that BSeI is a promising building block for constructing high‐performance polymer acceptors and stannylation of electron‐deficient building blocks offers an excellent approach to developing A–A type polymers for all‐PSCs and even beyond. [ABSTRACT FROM AUTHOR]

By changing the structures of the side chain on the backbone of the Y6 acceptor, many Y‐series acceptors have been synthesized to investigate the relationships between structures and properties of the fused‐ring electron acceptors (FREAs). However, not much attention has been paid to the effects of cycloalkane substituents on optoelectronic, morphological, and photovoltaic properties of the FREAs. Here, a brand‐new FREA D12 is developed by incorporating cyclohexylmethyl functional groups into the pyrrole rings of the backbone of the Y6 acceptor, and a similar compound E12 with the linear n‐heptane side chains is also synthesized for comparison. After the cyclization of the alkyl side‐chain, the molecular orientation of D12 exhibits favorable face‐on dominant, which endows D12 with higher charge mobility. Consequently, the organic solar cells (OSCs) with PM6 as donor and D12 as acceptor deliver the maximum power conversion efficiency of 17.3%, along with an excellent fill factor of 0.794, which is much higher than those of the PM6:E12‐based OSCs. The results reveal that introducing an inner cyclized alkyl chain on the pyrrole motif is a simple and feasible strategy to regulate molecular orientation and improve photovoltaic properties, which might provide guidelines for developing high‐performance electron acceptors. [ABSTRACT FROM AUTHOR]