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SARS-CoV-2, a novel coronavirus with high nucleotide identity to SARS-CoV and SARS-related coronaviruses detected in horseshoe bats, has spread across the world and impacted global healthcare systems and economy 1,2 . A suitable small animal model is needed to support vaccine and therapy development. We report the pathogenesis and transmissibility of the SARS-CoV-2 in golden Syrian hamsters. Immunohistochemistry demonstrated viral antigens in nasal mucosa, bronchial epithelial cells, and in areas of lung consolidation on days 2 and 5 post-inoculation (dpi), followed by rapid viral clearance and pneumocyte hyperplasia on 7 dpi. Viral antigen was also found in the duodenum epithelial cells with viral RNA detected in feces. Notably, SARS-CoV-2 transmitted efficiently from inoculated hamsters to naïve hamsters by direct contact and via aerosols. Transmission via fomites in soiled cages was less efficient. Although viral RNA was continuously detected in the nasal washes of inoculated hamsters for 14 days, the communicable period was short and correlated with the detection of infectious virus but not viral RNA. Inoculated and naturally-infected hamsters showed apparent weight loss, and all animals recovered with the detection of neutralizing antibodies. Our results suggest that SARS-CoV-2 infection in golden Syrian hamsters resemble features found in humans with mild infections.SARS-CoV-2 was first detected from a cluster of pneumonia patients in Wuhan, Hubei Province, China in December 2019. Although 55% of the initial cases were linked to one seafood wholesale market where wild animals were also sold 3 , multiple viral (sustained human-to-human transmissibility by symptomatic and pre-symptomatic patients 4 ) and ecological factors (extensive domestic and international travel during Chinese Lunar New Year) have contributed to the rapid global spread of the virus. The clinical spectrum of patients with the novel coronavirus disease (COVID-19) is wide, 19% of 72,314 symptomatic patients in China progressed to severe and critical illness 5 with an estimated 1.4% symptomatic case fatality risk 6 . There is no approved vaccine or treatment against SARS-CoV-2, and the available interventions including country lock-down and social distancing have severely disrupted the global supply chain and economy.A suitable animal model is essential for understanding the pathogenesis of this disease and for evaluating vaccine and therapeutic candidates. Previous animal studies on SARS-CoV suggested the importance of the interaction between the viral spike protein and the host angiotensin converting enzyme 2 (ACE2) receptors 7-10 as well as age and innate immune status of the animals 11-14 in pathogenesis. As with SARS-CoV, the spike protein of SARS-CoV-2 also utilizes ACE2 receptors that are distributed predominantly in the epithelial cells of the lungs and small intestine to gain entry into epithelial cells for viral replication 1,15 . SARS-CoV-2 showed good binding for human ACE2 but limited binding to murine ACE2 1 , which has limited...

We identified seasonal human coronaviruses, influenza viruses and rhinoviruses in exhaled breath and coughs of children and adults with acute respiratory illness. Surgical face masks significantly reduced detection of influenza virus RNA in respiratory droplets and coronavirus RNA in aerosols, with a trend toward reduced detection of coronavirus RNA in respiratory droplets. Our results indicate that surgical face masks could prevent transmission of human coronaviruses and influenza viruses from symptomatic individuals.Respiratory virus infections cause a broad and overlapping spectrum of symptoms collectively referred to as acute respiratory virus illnesses (ARIs) or more commonly the 'common cold' . Although mostly mild, these ARIs can sometimes cause severe disease and death 1 . These viruses spread between humans through direct or indirect contact, respiratory droplets (including larger droplets that fall rapidly near the source as well as coarse aerosols with aerodynamic diameter >5 µm) and fine-particle aerosols (droplets and droplet nuclei with aerodynamic diameter ≤5 µm) 2,3 . Although hand hygiene and use of face masks, primarily targeting contact and respiratory droplet transmission, have been suggested as important mitigation strategies against influenza virus transmission 4 , little is known about the relative importance of these modes in the transmission of other common respiratory viruses 2,3,5 . Uncertainties similarly apply to the modes of transmission of 7 ).Some health authorities recommend that masks be worn by ill individuals to prevent onward transmission (source control) 4,8 . Surgical face masks were originally introduced to protect patients from wound infection and contamination from surgeons (the wearer) during surgical procedures, and were later adopted to protect healthcare workers against acquiring infection from their patients. However, most of the existing evidence on the filtering efficacy of face masks and respirators comes from in vitro experiments with nonbiological particles 9,10 , which may not be generalizable to infectious respiratory virus droplets. There is little information on the efficacy of face masks in filtering respiratory viruses and reducing viral release from an individual with respiratory infections 8 , and most research has focused on influenza 11,12 .Here we aimed to explore the importance of respiratory droplet and aerosol routes of transmission with a particular focus on coronaviruses, influenza viruses and rhinoviruses, by quantifying the amount of respiratory virus in exhaled breath of participants with medically attended ARIs and determining the potential efficacy of surgical face masks to prevent respiratory virus transmission.

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 23.15 μM, 26.63 μM, 2.55 μM and 0.46 μM, respectively. Ribavirin or favipiravir that are currently evaluated under clinical trials showed no inhibition at 100 μM. Synergy between remdesivir and emetine was observed, and remdesivir at 6.25 μM in combination with emetine at 0.195 μM may achieve 64.9% inhibition in viral yield. Combinational therapy may help to reduce the effective concentration of compounds below the therapeutic plasma concentrations and provide better clinical benefits.

There are few studies describing the presence of respiratory viruses in respiratory droplets and aerosols in the exhaled breath of infected persons, and the efficacy of facemasks as a source control to prevent respiratory virus transmission. Here, we recruited children and adults with acute respiratory illness and collected respiratory droplets and aerosols, with and without surgical facemasks. We identified human coronaviruses, influenza virus and rhinovirus from both respiratory droplets and aerosols. Surgical face masks reduced detection of coronavirus RNA in both respiratory droplets and aerosols, but only respiratory droplets and not aerosols for influenza virus RNA. Our results provide mechanistic evidence that surgical facemasks could prevent transmission of human coronavirus and influenza virus infections if worn by symptomatic individuals.Authors Donald K Milton and Benjamin J Cowling are joint senior authors.

H5N1 influenza viruses transmitted from poultry to humans in Asia cause high mortality and pose a pandemic threat. Viral genes important for cell tropism and replication efficiency must be identified to elucidate and target virulence factors. We applied reverse genetics to generate H5N1 reassortants combining genes of lethal A/Vietnam/1203/04 (VN1203), a fatal human case isolate, and nonlethal A/chicken/Vietnam/C58/04 (CH58) and tested their pathogenicity in ferrets and mice. The viruses' hemagglutinins have six amino acids differences, identical cleavage sites, and avian-like α-(2,3)–linked receptor specificity. Surprisingly, exchanging hemagglutinin and neuraminidase genes did not alter pathogenicity, but substituting CH58 polymerase genes completely attenuated VN1203 virulence and reduced viral polymerase activity. CH58's NS gene partially attenuated VN1203 in ferrets but not in mice. Our findings suggest that for high virulence in mammalian species an avian H5N1 virus with a cleavable hemagglutinin requires adaptive changes in polymerase genes to overcome the species barrier. Thus, novel antivirals targeting polymerase proteins should be developed.

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Three type A influenza viruses, each of which has a distinct neuraminidase-gene mutation and is resistant to the neuraminidase inhibitor oseltamivir, have been isolated. Previously, in the ferret model, an R292K mutant of a type A (H3N2) virus was not transmitted under conditions in which the wild-type virus was transmitted. This model was used to investigate whether the E119V mutant of a type A (H3N2) virus and the H274Y mutant of a type A (H1N1) virus would be transmitted under similar circumstances. Both mutant viruses were transmitted, although the H274Y mutant required a 100-fold-higher dose for infection of donor ferrets and was transmitted more slowly than was the wild type. Both the mutant and the wild-type viruses retained their genotypic characteristics.