新型コロナウイルス感染における宿主因子EXOC2の機能解析

京都大学新制・課程博士博士(医科学)甲第25203号医科博第159号京都大学大学院医学研究科医科学専攻(主査)教授 濵﨑 洋子, 教授 中川 一路, 教授 竹内 理学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Exocyst complex component 2 is a potential host factor for SARS-CoV-2 infection

iPS細胞やオルガノイド技術を用いた新型コロナウイルス感染におけるEXOC2の機能解析. 京都大学プレスリリース. 2022-10-27.An important host factor in SARS-CoV-2 infection, identified using iPS cell and organoid technology. 京都大学プレスリリース. 2022-10-31.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an epidemic and spread rapidly all over the world. Because the analysis of host factors other than receptors and proteases has not been sufficiently performed, we attempted to identify and characterize host factors essential for SARS-CoV-2 infection using iPS cells and airway organoids (AO). Based on previous CRISPR screening and RNA-seq data, we found that exocyst complex component 2 (EXOC2) is one important host factor for SARS-CoV-2 infection. The intracellular SARS-CoV-2 nucleocapsid (N) expression level was decreased to 3.7 % and the virus copy number in cell culture medium was decreased to 1.6 % by EXOC2 knockdown. Consistently, immunostaining results showed that N protein-positive cells were significantly decreased by EXOC2 knockdown. We also found that EXOC2 knockdown downregulates SARS-CoV-2 infection by regulating IFNW1 expression. In conclusion, controlling the EXOC2 expression level may prevent SARS-CoV-2 infection and deserves further study

Dual inhibition of TMPRSS2 and Cathepsin B prevents SARS-CoV-2 infection in iPS cells

TMPRSS2とカテプシンBを標的とした新型コロナウイルスの感染阻害. 京都大学プレスリリース. 2021-10-21.A drug cocktail stops SARS-CoV-2 infection of stem cells. 京都大学プレスリリース. 2021-10-21.It has been reported that many receptors and proteases are required for SARS-CoV-2 infection. Although angiotensin-converting enzyme2 (ACE2) is the most important of these receptors, little is known about the contribution of other genes. In this study, we examined the roles of neuropilin-1, basigin, transmembrane serine proteases (TMPRSSs), and cathepsins (CTSs) in SARS-CoV-2 infection using the CRISPR interference system and ACE2-expressing human iPS cells. Double-knockdown of TMPRSS2 and CTSB reduced the viral load to 0.036±0.021%. Consistently, the combination of the CTPB inhibitor CA-074 methyl ester and the TMPRSS2 inhibitor Camostat reduced the viral load to 0.0078±0.0057%. This result was confirmed using four SARS-CoV-2 variants (B.1.3, B.1.1.7, B.1.351, and B.1.1.248). The simultaneous use of these two drugs reduced viral load to less than 0.01% in both female and male iPS cells. These findings suggest that compounds targeting TMPRSS2 and CTSB exhibit highly efficient antiviral effects independent of gender and SARS-CoV-2 variant

Scalable processing for realizing 21.7%-efficient all-perovskite tandem solar modules.

10.1126/science.abn7696Science3766594762-76

All-perovskite tandem solar cells with 24.2% certified efficiency and area over 1 cm2 using surface-anchoring zwitterionic antioxidant

Monolithic all-perovskite tandem solar cells offer an avenue to increase power conversion efficiency beyond the limits of single-junction cells. It is an important priority to unite efficiency, uniformity and stability, yet this has proven challenging because of high trap density and ready oxidation in narrow-bandgap mixed lead–tin perovskite subcells. Here we report simultaneous enhancements in the efficiency, uniformity and stability of narrow-bandgap subcells using strongly reductive surface-anchoring zwitterionic molecules. The zwitterionic antioxidant inhibits Sn2+ oxidation and passivates defects at the grain surfaces in mixed lead–tin perovskite films, enabling an efficiency of 21.7% (certified 20.7%) for single-junction solar cells. We further obtain a certified efficiency of 24.2% in 1-cm2-area all-perovskite tandem cells and in-lab power conversion efficiencies of 25.6% and 21.4% for 0.049 cm2 and 12 cm2 devices, respectively. The encapsulated tandem devices retain 88% of their initial performance following 500 hours of operation at a device temperature of 54–60 °C under one-sun illumination in ambient conditions.This work is financially supported by the National Natural Science Foundation of China (61974063, 61921005), Fundamental Research Funds for the Central Universities (14380168), National Key R&D Program of China (2018YFB1500102), Natural Science Foundation of Jiangsu Province (BK20190315), Basic Research Program of Frontier Leading Technologies in Jiangsu Province, Program for Innovative Talents and Entrepreneur in Jiangsu and Thousand Talent Program for Young Outstanding Scientists in China. The work of Y.H., M.W. and E.H.S. is supported by US Department of the Navy, Office of Naval Research (N00014-20-1-2572). V.Y. and M.I.S. acknowledge the support of the Natural Sciences and Engineering Research Council of Canada (NSERC)