Comparative study of the propagation and plaque titration conditions for human coronavirus OC43 as a surrogate for SARS-CoV-2.

The ongoing COVID-19 pandemic is threatening human health globally. The development of effective drugs and vaccines against SARS-CoV-2 is hindered by the limited access to high-biosafety-level facilities. Although human coronavirus (HCoV) OC43, a low-pathogenic endemic human coronavirus, has been used as a surrogate virus for SARS-CoV-2 research, a standard technique for HCoV-OC43 culture and plaque titration has not been established.

In vitro synergistic antiviral activity of repurposed drugs against enterovirus 71.

Enteroviruses cause viral diseases that are harmful to children. Hand, foot, and mouth disease (HFMD) with neurological complications is mainly caused by enterovirus 71 (EV71). Despite its clinical importance, there is no effective antiviral drug against EV71.

Identification of inositol monophosphatase as a broad-spectrum antiviral target of ivermectin.

Ivermectin has broad-spectrum antiviral activities. Despite the failure in clinical application of COVID-19, it can serve as a lead compound for the development of more effective broad-spectrum antivirals, for which a better understanding of its antiviral mechanisms is essential. We thus searched for potential novel targets of ivermectin in host cells by label-free thermal proteomic profiling using Huh-7 cells.

Antibody Response to Influenza Hemagglutinin Conserved Stalk Domain after Sequential Immunization with Old Vaccine Strains.

Hemagglutinin (HA) is the major envelope glycoprotein and antigen on the surface of influenza virions. The glycoprotein comprises a globular head and a stalk region. While immunodominant epitopes on influenza HA head are highly variable, the stalk domain is conserved.

Human Schlafen 11 inhibits influenza A virus production.

Schlafen (SLFN) proteins are a subset of interferon-stimulated early response genes with antiviral properties. An antiviral mechanism of SLFN11 was previously demonstrated in human immunodeficiency virus type 1 (HIV-1)-infected cells, and it was shown that SLFN11 inhibited HIV-1 virus production in a codon usage-specific manner. The codon usage patterns of many viruses are vastly different from those of their hosts.

and studies of potential inhibitors against Dengue viral protein NS5 Methyl Transferase from Ginseng and Notoginseng.

Background And Aim: Dengue is a potentially deadly tropical infectious disease transmitted by mosquito vector with no antiviral drug available to date Dengue NS5 protein is crucial for viral replication and is the most conserved among all four Dengue serotypes, making it an attractive drug target. Both Ginseng and Notoginseng extracts and isolates have been shown to be effective against various viral infections yet against Dengue Virus is understudied. We aim to identify potential inhibitors against Dengue NS5 Methyl transferase from small molecular compounds found in Ginseng and Notoginseng.

Analysis of Influenza A virus infection in human induced pluripotent stem cells (hiPSCs) and their derivatives.

Influenza A virus (IAV) infection in pregnant women is a major public health concern. However, the effect of IAV infection on human embryogenesis is still unclear. Here we show that human induced pluripotent stem cells (hiPSCs) and hiPSC-derived ectodermal, mesodermal and endodermal cells are susceptible to IAV infection.

Dynamics of Neutralizing Antibodies and Binding Antibodies to Domains of SARS-CoV-2 Spike Protein in COVID-19 Survivors.

Neutralizing antibody level is used to predict immune protection against SARS-CoV-2 infection. Spike protein of SARS-CoV-2 is a major target for virus-neutralizing antibody. A number of neutralizing epitopes were mapped on receptor binding domain (RBD) and N-terminal domain (NTD) of S1 subunit of the spike.

A Randomized Controlled Trial of Combined Ivermectin and Zinc Sulfate versus Combined Hydroxychloroquine, Darunavir/Ritonavir, and Zinc Sulfate among Adult Patients with Asymptomatic or Mild Coronavirus-19 Infection.

Introduction: Ivermectin, hydroxychloroquine (HQ), and darunavir/ritonavir are widely prescribed as an oral treatment for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection despite their uncertainty of clinical benefit. The objective is to determine the safety and the efficacies of two treatment regimens against SARS-CoV-2 infection.

Methods: We conducted an open-labeled, randomized, controlled trial to compare the efficacy between a 3-day course of once-daily high-dose oral ivermectin plus zinc sulfate (Group A) and a combination of HQ, darunavir/ritonavir, and zinc sulfate (HQ + antiretroviral, Group B) for 5 days in asymptomatic or mild SARS-CoV-2 infection.

Synergistic anti-SARS-CoV-2 activity of repurposed anti-parasitic drug combinations.

Background: COVID-19 pandemic has claimed millions of lives and devastated the health service system, livelihood, and economy in many countries worldwide. Despite the vaccination programs in many countries, the spread of the pandemic continues, and effective treatment is still urgently needed. Although some antiviral drugs have been shown to be effective, they are not widely available.

Microparticles from human the lower airway show inhibitory activity against respiratory syncytial virus.

Airway microparticles (MPs) have been shown previously to inhibit influenza virus by trapping virions on their surface through their surface viral receptor. It was hypothesized that airway MPs may carry most of the epithelial cell surface molecules, including receptors for respiratory viruses, and may be able to inhibit various respiratory viruses. We show here that MPs from human bronchoalveolar lavage (BAL) can inhibit respiratory syncytial virus (RSV).

Repurposing of antiparasitic niclosamide to inhibit respiratory syncytial virus (RSV) replication.

Despite being an important health problem, there are only supportive care treatments for respiratory syncytial virus (RSV) infection. Thus, discovery of specific therapeutic drugs for RSV is still needed. Recently, an antiparasitic drug niclosamide has shown a broad-spectrum antiviral activity.

Analysis of Tembusu virus infection of human cell lines and human induced pluripotent stem cell derived hepatocytes.

Tembusu virus (TMUV) causes disease in poultry, especially in ducks, resulting in abnormality in egg production and with high morbidity and mortality, resulting in great loss in duck farming industry in China and Southeast Asia. Previous studies on the pathogenesis of TMUV infection have been mostly conducted in poultry, with a few studies being undertaken in mice. While TMUV does not cause disease in humans, it has been reported that antibodies against TMUV have been found in serum samples from duck farmers, and thus data on TMUV infection in humans is limited, and the pathogenesis is unclear.

Inhibition of human immunodeficiency virus type 1 by niclosamide through mTORC1 inhibition.

Niclosamide has been known to inhibit a number of pH-dependent viruses via the neutralization of endosomal acidic pH. It has also been shown to disrupt the mTORC1 signaling pathway. The replication of many viruses requires mTORC1 activation.

Influence of cellular lipid content on influenza A virus replication.

Influenza A virus (IAV) depends on the metabolism of its cellular host to provide energy and essential factors, including lipids, for viral replication. Previous studies have shown that fatty acids (FAs) play an important role in IAV replication and that inhibition of FA biosynthesis can diminish viral replication. However, cellular lipids can either be synthesized intracellularly or be imported from the extracellular environment.

Immune response to influenza vaccination in ESRD patients undergoing hemodialysis vs. hemodiafiltration.

Background: On-line hemodiafiltration (HDF) clears more azotemic toxins compared to high-flux hemodialysis (HD). The response to vaccination is impaired in dialysis patients. We wished to determine whether the immune responses to influenza vaccine in dialysis patients treated by HDF were stronger than those treated by HD.

The relationship of codon usage to the replication strategy of parvoviruses.

Codon usage is biased in most species, and the pattern of codon usage bias is specific to each species or group of closely related species. Although viruses use the host translational machinery for synthesis of their proteins, their codon usage patterns do not match those of their host. Viral codon usage is determined by a complex interplay of mutational bias, genome composition constraints, translational adaptation to the host, and host cellular innate defense.

Genome polarity of RNA viruses reflects the different evolutionary pressures shaping codon usage.

RNA viruses are classified by their genome polarity and replication strategies. Nucleotide composition and codon usage differ among virus groups, for instance positive-sense RNA (+ssRNA) viruses have higher GC-content than the other RNA virus groups. Codon usage of +ssRNA viruses is closer to humans showing significantly higher codon adaptation index (CAI) than those of negative-sense RNA (-ssRNA), double stranded RNA (dsRNA) and retroviruses.

Microparticle Release from Cell Lines and Its Anti-Influenza Activity.

Microparticles (MPs) are vesicles that are released by budding from plasma membrane of living cells. Recently, the role of MPs in antiviral activity has been proposed. We investigated quantity and anti-influenza activity of MPs from human alveolar epithelial cells A549, human bronchial epithelial cells BEAS-2B, human colon adenocarcinoma cells HT-29, and the human lung fibroblast cells MRC-5.

H1N1 seasonal influenza virus evolutionary rate changed over time.

It was previously shown that the seasonal H1N1 influenza virus antigenic drift occurred at a slower rate than the seasonal H3N2 virus during the first decade of the 21th century. It was hypothesized that the slower antigenic evolution led to a decrease in average ages of infection, which in turn resulted in lower level of global viral circulation. It is unclear what caused the difference between the two viruses, but a plausible explanation may be related to the fact that the H1N1 virus had been in human population for much longer than the H3N2 virus.

Codon usage of HIV regulatory genes is not determined by nucleotide composition.

Codon usage bias can be a result of either mutational bias or selection for translational efficiency and/or accuracy. Previous data has suggested that nucleotide composition constraint was the main determinant of HIV codon usage, and that nucleotide composition and codon usage were different between the regulatory genes, tat and rev, and other viral genes. It is not clear whether translational selection contributed to the codon usage difference and how nucleotide composition and translational selection interact to determine HIV codon usage.

Microparticle and anti-influenza activity in human respiratory secretion.

Respiratory secretions, such as saliva and bronchoalveolar fluid, contain anti-influenza activity. Multiple soluble factors have been described that exert anti-influenza activity and are believed to be responsible for the anti-influenza activity in respiratory secretions. It was previously shown that a bronchial epithelial cell culture could produce exosome-like particles with anti-influenza activity.

Mutations in matrix protein 1 and nucleoprotein caused human-specific defects in nuclear exportation and viral assembly of an avian influenza H7N1 virus.

Nuclear exportation of influenza ribonucleoprotein is a vital step in viral replication cycle. In this study a particular H7N1 (A/ostrich/Zimbabwe/222-E3/1996) virus showed exclusively nuclear localization of the viral nucleoprotein (NP) only in human cell lines but not in cell lines of other species suggesting a human-specific nuclear exportation defect. After 10 passages in human lung cells, an adapted strain (H7N1:P10) could efficiently replicate and export viral NP in human cells.

Exposure to cold impairs interferon-induced antiviral defense.

It is commonly believed that exposure to low temperature increases susceptibility to viral infection in the human respiratory tract, but a molecular mechanism supporting this belief has yet to be discovered. In this study, we investigated the effect of low temperature on viral infection and innate defense in cell lines from the human respiratory tract and found that interferon-induced antiviral responses were impaired at low temperatures. Cells maintained at 25°C and 33°C expressed lower levels of myxovirus resistance protein 1 (MxA) and 2'5'-oligoadenylate synthetase 1 (OAS1) mRNAs when compared to cells maintained at 37°C after infection by seasonal influenza viruses.

Evolutionary dynamic of antigenic residues on influenza B hemagglutinin.

Hemagglutinin (HA) of seasonal influenza virus evolves under positive selection pressure exerted by host immunity. It was previously shown that antigenic drift in different influenza B sublineages during different time periods distributed unevenly among different epitopes, and that more recent viruses up to 2007 might have their antigenic drift more focused on certain epitope. We further analyzed whether more recent influenza B viruses up to 2016 followed that same pattern of antigenic evolution.