Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 [95% confidence interval (CI) 4.84–5.29] for men of European ancestry to 3.74 [95% CI 3.36–4.17] for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher [95% CI 2.14–2.22], and men of East Asian ancestry 0.73-times lower [95% CI 0.71–0.76], than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.

Coronavirus Disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a newly emerged coronavirus, and has been pandemic since March 2020 and led to many fatalities. Vaccines represent the most efficient means to control and stop the pandemic of COVID-19. However, currently there is no effective COVID-19 vaccine approved to use worldwide except for two human adenovirus vector vaccines, three inactivated vaccines, and one peptide vaccine for early or limited use in China and Russia. Safe and effective vaccines against COVID-19 are in urgent need. Researchers around the world are developing 213 COVID-19 candidate vaccines, among which 44 are in human trials. In this review, we summarize and analyze vaccine progress against SARS-CoV, Middle-East respiratory syndrome Coronavirus (MERS-CoV), and SARS-CoV-2, including inactivated vaccines, live attenuated vaccines, subunit vaccines, virus like particles, nucleic acid vaccines, and viral vector vaccines. As SARS-CoV-2, SARS-CoV, and MERS-CoV share the common genus, Betacoronavirus, this review of the major research progress will provide a reference and new insights into the COVID-19 vaccine design and development.

250 words 25 Importance: 150 words 26 Abstract 28 A novel coronavirus SARS-CoV-2 is associated with the current global pandemic of Coronavirus 29Disease 2019 . Spike protein receptor-binding domain (RBD) of SARS-CoV-2 is the 30 critical determinant of viral tropism and infectivity. To investigate whether the mutations in the RBD 31 have altered the receptor binding affinity and caused these strains more infectious, we performed 32 molecular dynamics simulations of the binding affinity between the mutant SARS-CoV-2 RBDs to 33 date and the human ACE2 receptor. Among 1609 genomes of global SARS-CoV-2 strains, 32 34 non-synonymous RBD mutants were identified and clustered into 9 mutant types under high positive 35 selection pressure. Three mutant types (V367F, W436R, and D364Y) emerging in Wuhan, Shenzhen, 36 Hong Kong, and France, displayed higher human ACE2 affinity, and probably higher infectivity. This 37 is due to the enhanced structural stabilization of the RBD beta-sheet scaffold. High frequencies of 38 RBD mutations were identified: V367F from five France and one Hong Kong mutants, 13 V483A and 39 7 G476S mutants from the U.S.A. This suggested they originated as novel sub-lineages. The 40 enhancement of the binding affinity of the mutant type (V367F) was further validated by the 41 receptor-ligand binding ELISA assay. The molecular dynamics simulations also indicated that it 42 would be difficult for bat SARS-like CoV to infect humans. However, the pangolin CoV is potentially 43 infectious to humans. The analysis of critical RBD mutations provides further insights into the 44 evolutionary history of SARS-CoV-2 under high selection pressure. An enhancement of the 45 SARS-CoV-2 binding affinity to human ACE2 receptor reveals higher infectivity of the mutant 46 strains. 47 48 Importance 49 A novel coronavirus SARS-CoV-2 has caused the pandemic of COVID-19. The origin of 50 SARS-CoV-2 was associated with zoonotic infections. The spike protein receptor-binding domain 51 (RBD) is identified as the critical determinant of viral tropism and infectivity. Thus, whether the 52 mutations in the RBD of the circulating SARS-CoV-2 strains have altered the receptor binding 53affinity and caused these strains more infectious, should be paid more attentions to. Here, 32 54 non-synonymous RBD mutants were identified and clustered into 9 mutant types under high positive 55 . CC-BY-NC-ND 4.0 International license (which was not certified by peer review) is the author/funder. It is made available under a selection pressure, suggesting they originated as novel sub-lineages. Three mutant types displayed 56 higher human ACE2 affinity, and probably higher infectivity, one of which (V367F) was validated 57 by wet bench. The RBD mutation analysis provides insights into SARS-CoV-2 evolution. The 58 emergence of RBD mutations with increased human ACE2 affinity reveals higher risk of severe 59 morbidity and mortality during a sustained COVID-19 pandemic, particularly if no effective 60 precautions are implemented. 61 62

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect many animal species, including minks, cats, and dogs. To gain insights into SARS-CoV-2 infections in cats and dogs, we developed and validated a set of serologic assays, including ELISA and virus neutralization. Evaluation of samples from animals before they acquired coronavirus disease and samples from cats roaming SARS-CoV-2–positive mink farms confirmed the suitability of these assays for specific antibody detection. Furthermore, our findings exclude SARS-CoV-2 nucleocapsid protein as an antigen for serologic screening of cat and dog samples. We analyzed 500 serum samples from domestic cats and dogs in the Netherlands during April–May 2020. We showed 0.4% of cats and 0.2% of dogs were seropositive. Although seroprevalence in cats and dogs that had unknown SARS-CoV-2 exposure was low during the first coronavirus disease wave, our data stress the need for development of continuous serosurveillance for SARS-CoV-2 in these 2 animal species.