SARS-CoV-2 infection aggravates cigarette smoke-exposed cell damage in primary human airway epithelia.

Background: The coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide pandemic with over 627 million cases and over 6.5 million deaths. It was reported that smoking-related chronic obstructive pulmonary disease (COPD) might be a crucial risk for COVID-19 patients to develop severe condition.

Human liver organoid derived intra-hepatic bile duct cells support SARS-CoV-2 infection and replication.

Although the main route of infection for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the respiratory tract, liver injury is also commonly seen in many patients, as evidenced by deranged parenchymal liver enzymes. Furthermore, the severity of liver damage has been shown to correlate with higher mortality. Overall, the mechanism behind the liver injury remains unclear.

Simeprevir Potently Suppresses SARS-CoV-2 Replication and Synergizes with Remdesivir.

The outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global threat to human health. Using a multidisciplinary approach, we identified and validated the hepatitis C virus (HCV) protease inhibitor simeprevir as an especially promising repurposable drug for treating COVID-19. Simeprevir potently reduces SARS-CoV-2 viral load by multiple orders of magnitude and synergizes with remdesivir .

Role of Epithelial-Endothelial Cell Interaction in the Pathogenesis of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection.

Background: The coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to threaten public health globally. Patients with severe COVID-19 disease progress to acute respiratory distress syndrome, with respiratory and multiple organ failure. It is believed that dysregulated production of proinflammatory cytokines and endothelial dysfunction contribute to the pathogenesis of severe diseases.

Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro.

An escalating pandemic by the novel SARS-CoV-2 virus is impacting global health and effective therapeutic options are urgently needed. We evaluated the in vitro antiviral effect of compounds that were previously reported to inhibit coronavirus replication and compounds that are currently under evaluation in clinical trials for SARS-CoV-2 patients. We report the antiviral effect of remdesivir, lopinavir, homorringtonine, and emetine against SARS-CoV-2 virus in Vero E6 cells with the estimated 50% effective concentration at 23.

Cell Cycle-independent Role of Cyclin D3 in Host Restriction of Influenza Virus Infection.

To identify new host factors that modulate the replication of influenza A virus, we performed a yeast two-hybrid screen using the cytoplasmic tail of matrix protein 2 from the highly pathogenic H5N1 strain. The screen revealed a high-score interaction with cyclin D3, a key regulator of cell cycle early G phase. M2-cyclin D3 interaction was validated through GST pull-down and recapitulated in influenza A/WSN/33-infected cells.

Anti-inflammatory effects of indirubin derivatives on influenza A virus-infected human pulmonary microvascular endothelial cells.

Influenza A virus (IAV) poses global threats to human health. Acute respiratory distress syndrome and multi-organ dysfunction are major complications in patients with severe influenza infection. This may be explained by the recent studies which highlighted the role of the pulmonary endothelium as the center of innate immune cells recruitment and excessive pro-inflammatory cytokines production.

Amino acid substitutions in polymerase basic protein 2 gene contribute to the pathogenicity of the novel A/H7N9 influenza virus in mammalian hosts.

Unlabelled: A novel avian-origin influenza A/H7N9 virus emerged in 2013 to cause more than 130 cases of zoonotic human disease, with an overall case fatality rate of around 30% in cases detected. It has been shown that an E-to-K amino acid change at residue 627 of polymerase basic protein 2 (PB2) occurred frequently in the H7N9 isolates obtained from humans but not in viruses isolated from poultry. Although this mutation has been reported to confer increased mammalian pathogenicity in other avian influenza subtypes, it has not been experimentally investigated in the H7N9 virus.

Pathogenicity of the novel A/H7N9 influenza virus in mice.

Unlabelled: A novel avian-origin influenza A/H7N9 virus infecting humans was first identified in March 2013 and, as of 30 May 2013, has caused 132 human infections leading to 33 deaths. Phylogenetic studies suggest that this virus is a reassortant, with the surface hemagglutinin (HA) and neuraminidase (NA) genes being derived from duck and wild-bird viruses, respectively, while the six "internal gene segments" were derived from poultry H9N2 viruses. Here we determine the pathogenicity of a human A/Shanghai/2/2013 (Sh2/H7N9) virus in healthy adult mice in comparison with that of A/chicken/Hong Kong/HH8/2010 (ck/H9N2) virus, highly pathogenic avian influenza (HPAI) A/Hong Kong/483/1997 (483/H5N1) virus, and a duck influenza A H7N9 virus of different genetic derivation, A/duck/Jiangxi/3286/2009 (dk/H7N9).

Dual functions of ginsenosides in protecting human endothelial cells against influenza H9N2-induced inflammation and apoptosis.

Ethnopharmacological Relevance: Panax ginseng is a precious traditional Chinese herbal medicine which has been utilized as herbal tonic for improving immunity. The active component, ginsenosides have been shown to possess various pharmacological functions including immunomodulation and cardiovascular protection.

Aim Of The Study: To investigate the immunomodulatory effect and anti-apoptotic effect of ginsenosides on avian influenza-infected human endothelial cells, and to present evidence for the cardiovascular protection by ginseng during influenza infection.

Amino acid residues 253 and 591 of the PB2 protein of avian influenza virus A H9N2 contribute to mammalian pathogenesis.

We investigated the tropism, host responses, and virulence of two variants of A/Quail/Hong Kong/G1/1997 (H9N2) (H9N2/G1) with D253N and Q591K in the PB2 protein in primary human macrophages and bronchial epithelium in vitro and in mice in vivo. Virus with PB2 D253N and Q591K had greater polymerase activity in minireplicon assays, induced more tumor necrosis factor alpha (TNF-α) in human macrophages, replicated better in differentiated normal human bronchial epithelial (NHBE) cells, and was more pathogenic for mice. Taken together, our studies help define the viral genetic determinants that contribute to pathogenicity of H9N2 viruses.