B-Cell-Epitope-Based Fluorescent Quantum Dot Biosensors for SARS-CoV-2 Enable Highly Sensitive COVID-19 Antibody Detection.

A new antibody diagnostic assay with more rapid and robust properties is demanded to quantitatively evaluate anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunity in a large population. Here, we developed a nanometer-scale fluorescent biosensor system consisting of CdSe-ZnS quantum dots (QDs) coupled with the highly sensitive B-cell epitopes of SARS-CoV-2 that could remarkably identify the corresponding antibody with a detection limit of 100 pM. Intriguingly, we found that fluorescence quenching of QDs was stimulated more obviously when coupled with peptides than the corresponding proteins, indicating that the energy transfer between QDs and peptides was more effective. Compared to the traditional enzyme-linked immunosorbent assay (ELISA), the B-cell-epitope-based QD-biosensor could robustly distinguish coronavirus disease 2019 (COVID-19) antibody-positive patients from uninfected individuals with a higher sensitivity (92.3-98.1% positive rates by QD-biosensor vs. 78.3-83.1% positive rates by ELISAs in 207 COVID-19 patients' sera) in a more rapid (5 min) and labor-saving manner. Taken together, the 'QD-peptides' biosensor provided a novel real-time, quantitative, and high-throughput method for clinical diagnosis and home-use tests.

A Broad Antiviral Strategy: Inhibitors of Human DHODH Pave the Way for Host-Targeting Antivirals against Emerging and Re-Emerging Viruses.

New strategies to rapidly develop broad-spectrum antiviral therapies are urgently required for emerging and re-emerging viruses. Host-targeting antivirals (HTAs) that target the universal host factors necessary for viral replication are the most promising approach, with broad-spectrum, foresighted function, and low resistance. We and others recently identified that host dihydroorotate dehydrogenase (DHODH) is one of the universal host factors essential for the replication of many acute-infectious viruses. DHODH is a rate-limiting enzyme catalyzing the fourth step in de novo pyrimidine synthesis. Therefore, it has also been developed as a therapeutic target for many diseases relying on cellular pyrimidine resources, such as cancers, autoimmune diseases, and viral or bacterial infections. Significantly, the successful use of DHODH inhibitors (DHODHi) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection further supports the application prospects. This review focuses on the advantages of HTAs and the antiviral effects of DHODHi with clinical applications. The multiple functions of DHODHi in inhibiting viral replication, stimulating ISGs expression, and suppressing cytokine storms make DHODHi a potent strategy against viral infection.

The Role of Ubiquitination in NF-κB Signaling during Virus Infection.

The nuclear factor κB (NF-κB) family are the master transcription factors that control cell proliferation, apoptosis, the expression of interferons and proinflammatory factors, and viral infection. During viral infection, host innate immune system senses viral products, such as viral nucleic acids, to activate innate defense pathways, including the NF-κB signaling axis, thereby inhibiting viral infection. In these NF-κB signaling pathways, diverse types of ubiquitination have been shown to participate in different steps of the signal cascades. Recent advances find that viruses also modulate the ubiquitination in NF-κB signaling pathways to activate viral gene expression or inhibit host NF-κB activation and inflammation, thereby facilitating viral infection. Understanding the role of ubiquitination in NF-κB signaling during viral infection will advance our knowledge of regulatory mechanisms of NF-κB signaling and pave the avenue for potential antiviral therapeutics. Thus, here we systematically review the ubiquitination in NF-κB signaling, delineate how viruses modulate the NF-κB signaling via ubiquitination and discuss the potential future directions.

Neurologic Manifestations of the World Health Organization's List of Pandemic and Epidemic Diseases.

The World Health Organization (WHO) monitors the spread of diseases globally and maintains a list of diseases with epidemic or pandemic potential. Currently listed diseases include Chikungunya, cholera, Crimean-Congo hemorrhagic fever, Ebola virus disease, Hendra virus infection, influenza, Lassa fever, Marburg virus disease, Neisseria meningitis, MERS-CoV, monkeypox, Nipah virus infection, novel coronavirus (COVID-19), plague, Rift Valley fever, SARS, smallpox, tularemia, yellow fever, and Zika virus disease. The associated pathogens are increasingly important on the global stage. The majority of these diseases have neurological manifestations. Those with less frequent neurological manifestations may also have important consequences. This is highlighted now in particular through the ongoing COVID-19 pandemic and reinforces that pathogens with the potential to spread rapidly and widely, in spite of concerted global efforts, may affect the nervous system. We searched the scientific literature, dating from 1934 to August 2020, to compile data on the cause, epidemiology, clinical presentation, neuroimaging features, and treatment of each of the diseases of epidemic or pandemic potential as viewed through a neurologist's lens. We included articles with an abstract or full text in English in this topical and scoping review. Diseases with epidemic and pandemic potential can be spread directly from human to human, animal to human, via mosquitoes or other insects, or via environmental contamination. Manifestations include central neurologic conditions (meningitis, encephalitis, intraparenchymal hemorrhage, seizures), peripheral and cranial nerve syndromes (sensory neuropathy, sensorineural hearing loss, ophthalmoplegia), post-infectious syndromes (acute inflammatory polyneuropathy), and congenital syndromes (fetal microcephaly), among others. Some diseases have not been well-characterized from a neurological standpoint, but all have at least scattered case reports of neurological features. Some of the diseases have curative treatments available while in other cases, supportive care remains the only management option. Regardless of the pathogen, prompt, and aggressive measures to control the spread of these agents are the most important factors in lowering the overall morbidity and mortality they can cause.

Coinfection with influenza A virus enhances SARS-CoV-2 infectivity.

The upcoming flu season in the Northern Hemisphere merging with the current COVID-19 pandemic raises a potentially severe threat to public health. Through experimental coinfection with influenza A virus (IAV) and either pseudotyped or live SARS-CoV-2 virus, we found that IAV preinfection significantly promoted the infectivity of SARS-CoV-2 in a broad range of cell types. Remarkably, in vivo, increased SARS-CoV-2 viral load and more severe lung damage were observed in mice coinfected with IAV. Moreover, such enhancement of SARS-CoV-2 infectivity was not observed with several other respiratory viruses, likely due to a unique feature of IAV to elevate ACE2 expression. This study illustrates that IAV has a unique ability to aggravate SARS-CoV-2 infection, and thus, prevention of IAV infection is of great significance during the COVID-19 pandemic.

Preliminary Assessment of the COVID-19 Outbreak Using 3-Staged Model e-ISHR.

The outbreak of coronavirus disease 2019 (COVID-19) in Wuhan has aroused widespread concern and attention from all over the world. Many articles have predicted the development of the epidemic. Most of them only use very basic SEIR model without considering the real situation. In this paper, we build a model called e-ISHR model based on SEIR model. Then we add hospital system and time delay system into the original model to simulate the spread of COVID-19 better. Besides, in order to take the government's control and people's awareness into consideration, we change our e-ISHR model into a 3-staged model which effectively shows the impact of these factors on the spread of the disease. By using this e-ISHR model, we fit and predict the number of confirmed cases in Wuhan and China except Hubei. We also change some of parameters in our model. The results indicate the importance of isolation and increasing the number of beds in hospital.