Among seven coronaviruses that infect humans, three (SARS-CoV, MERS-CoV, and the newly identified SARS-CoV-2) are associated with a severe, life-threatening respiratory infection and multiorgan failure. We previously proposed that the cationically modified chitosan, N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC) is a potent inhibitor of HCoV-NL63. Next, we demonstrated the broad-spectrum antiviral activity of the compound, as it inhibited all low pathogenic human coronaviruses (HCoV-NL63, HCoV-229E, HCoV-OC43, and HCoV-HKU1). Here, using in vitro and ex vivo model of human airway epithelium, we show that HTCC effectively blocks MERS-CoV and SARS-CoV-2 infection. We also confirmed the mechanism of action for these two viruses, showing that the polymer blocks the virus entry to the host cell by interaction with the S protein. IMPORTANCE The beginning of 2020 brought us information about the novel coronavirus emerging in China. Rapid research resulted in the characterization of the pathogen, which appeared to be a member of the SARS-like cluster, commonly seen in bats. Despite the global and local efforts, the virus escaped the health care measures and rapidly spread in China and later globally, officially causing a pandemic and global crisis in March 2020. At present, different scenarios are being written to contain the virus, but the development of novel anticoronavirals for all highly pathogenic coronaviruses remains the major challenge. Here, we describe the antiviral activity of previously developed by us HTCC compound, which may be used as a potential inhibitor of currently circulating highly pathogenic coronaviruses – SARS-CoV-2 and MERS-CoV.

38The beginning of 2020 brought us information about the novel coronavirus emerging in China. 39Rapid research resulted in the characterization of the pathogen, which appeared to be a member 40 of the SARS-like cluster, commonly seen in bats. Despite the global and local efforts, the virus 41 escaped the healthcare measures and rapidly spread in China and later globally, officially 42 causing a pandemic and global crisis in March 2020. At present, different scenarios are being 43 written to contain the virus, but the development of novel anticoronavirals for all highly 44 pathogenic coronaviruses remains the major challenge. Here, we describe the antiviral activity 45 of previously developed by us HTCC compound (N-(2-hydroxypropyl)-3-trimethylammonium 46 chitosan chloride), which may be used as potential inhibitor of currently circulating highly 47

Background In Poland, the clinical characteristics and outcomes of patients with COVID-19 requiring extracorporeal membrane oxygenation (ECMO) remain unknown. This study aimed to answer these unknowns by analyzing data collected from high-volume ECMO centers willing to participate in this project. Methods This retrospective, multicenter cohort study was completed between March 1, 2020, and May 31, 2021 (15 months). Data from all patients treated with ECMO for COVID-19 were analyzed. Pre-ECMO laboratory and treatment data were compared between non-survivors and survivors. Independent predictors for death in the intensive care unit (ICU) were identified. Results There were 171 patients admitted to participating centers requiring ECMO for refractory hypoxemia due to COVID-19 during the defined time period. A total of 158 patients (mean age: 46.3 ± 9.8 years) were analyzed, and 13 patients were still requiring ECMO at the end of the observation period. Most patients (88%) were treated after October 1, 2020, 77.8% were transferred to ECMO centers from another facility, and 31% were transferred on extracorporeal life support. The mean duration of ECMO therapy was 18.0 ± 13.5 days. The crude ICU mortality rate was 74.1%. In the group of 41 survivors, 37 patients were successfully weaned from ECMO support and four patients underwent a successful lung transplant. In-hospital death was independently associated with pre-ECMO lactate level (OR 2.10 per 1 mmol/L, p = 0.017) and BMI (OR 1.47 per 5 kg/m2, p = 0.050). Conclusions The ICU mortality rate among patients requiring ECMO for COVID-19 in Poland was high. In-hospital death was independently associated with increased pre-ECMO lactate levels and BMI.

35Human coronavirus HKU1 (HCoV-HKU1) is associated with respiratory disease and is 36 prevalent worldwide, but in vitro model for virus replication is lacking. Interaction between the 37 coronaviral spike (S) protein and its receptor is the major determinant of virus tissue and host 38 specificity, but virus entry is a complex process requiring a concerted action of multiple cellular 39 elements. Here, we show that KLK13 is required for the infection of the human respiratory 40 epithelium and is sufficient to mediate the entry of HCoV-HKU1 to non-permissive RD cells. 41 We also demonstrated HCoV-HKU1 S protein cleavage by KLK13 in the S1/S2 region, proving 42 that KLK13 is the priming enzyme for this virus. Summarizing, we show for the first time that 43 protease distribution and specificity predetermines the tissue and cell specificity of the virus 44 and may also regulate interspecies transmission. It is also of importance that presented data may 45 be relevant for the emerging coronaviruses, including SARS-CoV-2 and may help to understand 46 the differences in their zoonotic potential. : bioRxiv preprint 48Coronaviruses are the largest group within the order Nidovirales. Mainly, they cause 49 respiratory and enteric diseases in humans and animals, but some can cause more serious 50 conditions such as hepatitis, peritonitis, or neurological disease. Seven coronaviruses infect 51 humans, four of which (human coronavirus [HCoV]-229E, HCoV-NL63, HCoV-OC43, and 52 HCoV-HKU1) cause relatively mild upper and lower respiratory tract disease and two (SARS-53 CoV and MERS-CoV) are associated with severe, life-threatening respiratory infections and 54 multiorgan failure (1-6). Furthermore, in December 2019 a novel coronavirus SARS-CoV-2 55 emerged in Hubei province, China, causing pneumonia. To date, almost 90,000 cases were 56 identified and 3,000 patients died worldwide. 57 Coronaviral infection is initiated by interaction between the trimeric spike (S) protein 58 and its receptor, which is expressed on the surface of the susceptible cell. A number of adhesion 59 and entry receptors have been described for coronaviruses. For example, HCoV-229E (similar 60 to many other alphacoronaviruses) utilizes aminopeptidase N (APN) as the primary entry port 61 (7). Surprisingly, its cousin HCoV-NL63 shares receptor specificity with the evolutionarily 62 distant SARS-CoV and SARS-CoV-2: all hijack angiotensin-converting enzyme 2 (ACE2) (8-63 11). HCoV-NL63 was also shown to use heparan sulfate as a primary attachment site (12-14). 64 A very different receptor is recognized by MERS-CoV, which binds to dipeptidyl-peptidase 4 65 (DPP4) (9, 15, 16). Another betacoronavirus, HCoV-OC43, binds to N-acetyl-9-O-66 acetylneuraminic acid (17, 18). HCoV-HKU1 remains the great unknown because its cellular 67 receptor has not been identified and all efforts to culture the virus in vitro have failed.68 HCoV-HKU1 was identified in Hong Kong in 2004. The virus was present in a sample 69 obtained from an elderly patient with severe pneumonia (...

Background: Berberine (BBR) is an isoquinoline alkaloid which exhibits a variety of biological and therapeutic properties, and has been reported by some to block replication of the influenza virus. However, contradictory results have also been presented, and the mechanistic explanation is lacking. Methods: A panel of cell lines (Madin-Darby canine kidney (MDCK), adenocarcinoma human alveolar basal epithelial cells (A549), lung epithelial type I (LET1)) and primary human airway epithelial cells (HAE) susceptible to influenza virus infection were infected with a seasonal influenza A virus in the presence or absence of BBR. Cytotoxicity towards cell lines was measured using XTT assay. The yield of the virus was analyzed using RT-qPCR. To study the molecular mechanism of BBR, confocal microscopy and Western blot analyses of cellular fractions were applied. Results and conclusions: Our results show cell-type-dependent anti-influenza properties of BBR in vitro which suggests that the compound acts on the cell and not the virus. Importantly, BBR hampers influenza replication in primary human airway epithelium 3D cultures that mimic the natural replication site of the virus. Studies show that the influenza A virus upregulates the mitogen-activated protein kinase/extracellular signal-related kinase (MAPK/ERK) pathway and hijacks this pathway for nucleolar export of the viral ribonucleoprotein. Our results suggest that BBR interferes with this process and hampers influenza A replication.

Objectives: Lung transplantation not only saves a patient's life but also creates the opportunity for becoming more self-reliant and getting back to work. The aim of this single center study was to assess the prospects of employment, as well as its influence on the quality of life and physical activity, of the lung transplant recipients of the Silesian Center for Heart Diseases in Zabrze, Poland. Material and Methods: A retrospective study covered 67 lung transplant recipients of the Silesian Center of Heart Diseases. Only patients with ≥ 6-month follow-up were included. All of the patients gave their written consent to be included in the study before filling out the questionnaire containing questions about employment, income, education and how work affected their quality of life before and after lung transplantation. A physical capability assessment was performed by climbing flights of stairs and by means of a 6-min walk test, and spirometry parameters were also measured. Results: Twenty of the patients included in the study (31.7%) were employed after lung transplantation, 63.2% of whom worked full-time. Profession was changed by 2 patients (14.3%). The patients diagnosed with cystic fibrosis were found to have the highest chance of finding employment after lung transplantation. The statistical analysis revealed that the employed patients were able to cover longer distances during the 6-min walk test (556 m, on average) than the unemployed ones (494 m, on average). Conclusions: One in 3 patients finds employment after lung transplantation. Work improves the quality of life of the majority of lung transplant recipients. The patients who are employed are also in a better physical condition, and they are more self-reliant in comparison to those who remain unemployed. Lung transplant recipients with cystic fibrosis are most likely to find employment, and so are patients with higher education. Int J Occup

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