Little to no expression of angiotensin-converting enzyme-2 on most human peripheral blood immune cells but highly expressed on tissue macrophages.

Angiotensin-converting enzyme-2 (ACE2) has been recognized as the binding receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Flow cytometry demonstrated that there was little to no expression of ACE2 on most of the human peripheral blood-derived immune cells including CD4+ T, CD8+ T, activated CD4+ /CD8+ T, Tregs, Th17, NKT, B, NK cells, monocytes, dendritic cells, and granulocytes. There was no ACE2 expression on platelets and very low level of ACE2 protein expression on the surface of human primary pulmonary alveolar epithelial cells. The ACE2 expression was markedly upregulated on the activated type 1 macrophages (M1). Immunohistochemistry demonstrated high expressions of ACE2 on human tissue macrophages, such as alveolar macrophages, Kupffer cells within livers, and microglial cells in brain at steady state. The data suggest that alveolar macrophages, as the frontline immune cells, may be directly targeted by the SARS-CoV-2 infection and therefore need to be considered for the prevention and treatment of COVID-19.

Hydrogen bonding penalty used for virtual screening to discover potent inhibitors for Papain-Like cysteine proteases of SARS-CoV-2.

The Papain-Like proteases (PLpro) of SARS-CoV-2 play a crucial role in viral replication and the formation of nonstructural proteins. To find available inhibitors, the 3D structure of PLpro of SARS2 was obtained by homologous modelling, and we used this structure as a target to search for inhibitors through molecular docking and MM/GBSA binding free energy rescoring. A novel hydrogen bonding penalty was applied to the screening process, which meanwhile took desolvation into account. Finally, 61 compounds were acquired and 4 of them with IC50 at micromolar level tested in vitro enzyme activity assay, which includes clinical drugs tegaserod. Considering the importance of crystal water molecules, the 4 compounds were re-docked and considered bound waters in the active site as a part of PLpro. The binding modes of these 4 compounds were further explored with metadynamics simulations. The hits will provide a starting point for future key interactions identified and lead optimization targetting PLpro.

Investigation of an overseas COVID-19 misdiagnosed as dengue fever in Guangzhou

Analysis of a case of COVID-19 and dengue fever misdiagnosed key links, we provide basis for the development of COVID-19 prevention and control strategy in the epidemic period of dengue fever. We used descriptive epidemiological method to investigate and analyze the case, their close contacts and suspected sources of infection, tested SARS-CoV-2 by RT-PCR and dengue virus antigen and antibody by immunochromatography. The case had lived in Wuhan and Cambodia 14 days, and was diagnosed as suspected dengue fever in overseas hospital on January 23rd, 2020. On January 30, dengue antigen NS1 of the patient was tested suspiciously positive in an outpatient clinic in a "group hospital" in Cambodia, and negative for dengue antibodies IgM and IgG. The patient was diagnosed as "suspected dengue fever". In the early morning of January 31, the case entered Guangzhou and was quarantined in a hotel for observation. Blood samples were collected by medical staff at the hotel and sent to the Center for Disease Control and Prevention in Haizhu District for dengue fever detection by immunochromatography (colloidal gold). The results showed that the Dengue virus NS1 antigen was negative, IgM and IgG antibodies were negative, and "dengue fever" was excluded. On January 31, the hospital took a throat swab sample and the result was positive from SARS-CoV-2 nucleic acid test, which was reported as a "suspected COVID-19 case" on the network. On February 1, the Guangzhou Municipal Center for Disease Control and Prevention reviewed SARS-CoV-2 nucleic acid test and revised it as a "confirmed COVID-19 case". Some early symptoms of COVID-19 are similar with dengue fever. In the epidemic period of dengue fever, it is very important to make a good early diagnosis between dengue fever and COVID-19, early diagnosis and treatment is the key to prevent the spread of disease epidemic.