The ongoing coronavirus disease 2019 (COVID-19) pandemic has caused >20 million infections and >750,000 deaths. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, has been found closely related to the bat coronavirus strain RaTG13 (Bat-CoV RaTG13) and a recently identified pangolin coronavirus (Pangolin-CoV-2020). Here we first investigated the ability of SARS-CoV-2 and three related coronaviruses to utilize animal orthologs of angiotensin-converting enzyme 2 (ACE2) for cell entry. We found that ACE2 orthologs of a wide range of domestic and wild mammals, including camels, cattle, horses, goats, sheep, cats, rabbits and pangolins, were able to support cell entry of SARS-CoV-2, suggesting that these species might be able to harbor and spread this virus. In addition, the pangolin and bat coronaviruses, Pangolin-CoV-2020 and Bat-CoV RaTG13, were also found able to utilize human ACE2 and a number of animal-ACE2 orthologs for cell entry, indicating risks of spillover of these viruses into humans in the future. We then developed potently anti-coronavirus ACE2-Ig proteins that are broadly effective against the four distinct coronaviruses. In particular, through truncating ACE2 at its residue 740 but not 615, introducing a D30E mutation, and adopting an antibody-like tetrameric-ACE2 configuration, we generated an ACE2-Ig variant that neutralizes SARS-CoV-2 at picomolar range. These data demonstrate that the improved ACE2-Ig variants developed in this study could potentially be developed to protect from SARS-CoV-2 and some other SARS-like viruses that might spillover into humans in the future. IMPORTANCE The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the currently uncontrolled coronavirus disease 2019 (COVID-19) pandemic. It is important to study the host range of SARS-CoV-2 because some domestic species might harbor the virus and transmit it back to humans. In addition, insight into the ability of SARS-CoV-2 and SARS-like viruses to utilize animal orthologs of the SARS-CoV-2 receptor ACE2 might provide structural insight into improving ACE2-based viral entry inhibitors. In this study, we found that ACE2 orthologs of a wide range of domestic and wild animals can support cell entry of SARS-CoV-2 and three related coronaviruses, providing insights into identifying animal hosts of these viruses. We also developed recombinant ACE2-Ig proteins that are able to potently block these viral infections, providing a promising approach to developing antiviral proteins broadly effective against these distinct coronaviruses.

Background: As a neutral lipid and prominent component of the Western diet, cholesterol levels might be a risk factor for prostate cancer. However, current evidence has been inconsistent. This meta-analysis aimed to evaluate the association between blood cholesterol levels and the risk of prostate cancer.Methods: An extensive search was performed in MEDLINE and EMBASE for prospective studies that have reported the association between total cholesterol (TC), high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol (LDL) levels in blood and risk of prostate cancer. Random-effects models were used to summarize the study-specific results.Results: Fourteen studies were included in this meta-analysis. In the meta-analysis, the summarized risk ratios (RR) for the highest to lowest cholesterol levels were as follows: 1.05 [95%

1The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a currently uncontrolled 2 pandemic and the etiological agent of coronavirus disease 2019 . It is important to study 3 the host range of SARS-CoV-2 because some domestic species might harbor the virus and transmit it 4 back to humans. In addition, insight into the ability of SARS-CoV-2 and SARS-like viruses to utilize 5 animal orthologs of the SARS-CoV-2 receptor ACE2 might provide structural insight into improving 6 ACE2-based viral entry inhibitors. Here we show that ACE2 orthologs of a wide range of domestic 7 and wild animals support entry of SARS-CoV-2, as well as that of SARS-CoV-1, bat coronavirus 8 RaTG13, and a coronavirus isolated from pangolins. Some of these species, including camels, cattle, 9 horses, goats, sheep, pigs, cats, and rabbits may serve as potential intermediate hosts for new human 10 transmission, and rabbits in particular may serve as a useful experimental model of COVID-19. We 11show that SARS-CoV-2 and SARS-CoV-1 entry could be potently blocked by recombinant IgG Fc-12 fusion proteins of viral spike protein receptor-binding domains (RBD-Fc) and soluble ACE2 (ACE2-13 Fc). Moreover, an ACE2-Fc variant, which carries a D30E mutation and has ACE2 truncated at its 14 residue 740 but not 615, outperforms all the other ACE2-Fc variants on blocking entry of both viruses. 15 Our data suggest that RBD-Fc and ACE2-Fc could be used to treat and prevent infection of SARS-16 CoV-2 and any new viral variants that emerge over the course of the pandemic. 17 19 coronavirus, SADS-CoV) and betacoronaviruses (e.g. SARS coronavirus 1, SARS-CoV-1), infect 20 mammals and have broad host ranges spanning bats, rodents, domestic animals, and humans 1-7 . Bats 21 are considered to be the natural reservoir hosts for a number of pathogenic human coronaviruses, 22 including SARS-CoV-1, Middle East respiratory syndrome coronavirus (MERS-CoV), HCoV-NL63, 23 and HCoV-229E 6,8 . Domestic animals have been shown to play key roles as intermediate hosts, such 24 as camels for MERS-CoV and camelids for HCoV-229E, to transmit coronaviruses from bats to 25 humans 6 . The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent 26 of coronavirus disease 2019 (COVID-19) 8-10 , shares 79.5% genome sequence identity to SARS-CoV-27 1 and 96.2% genome sequence identity to a bat coronavirus, Bat-CoV RaTG13, indicating that bats 28 are also likely the reservoir hosts for SARS-CoV-2 ref.8-10 . However, it is unknown whether domestic 29 was not certified by peer review) : bioRxiv preprint animals also served as intermediate hosts that facilitated SARS-CoV-2 transmission from its natural 30 reservoir hosts to humans. 31 As of April 7 th 2020, the uncontrolled COVID-19 pandemic has already caused over 1,210,000 32 confirmed infections and over 67,000 documented deaths across 211 countries, according to World 33 Health Organization's online updates. There are currently no vaccines or targeted therapeutics 34 available for this disease 11 . ...