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2022 Vol. 13, No. 12

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Severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) infection elicits an initial inflammatory immune response and leads to pneumonia and acute respiratory distress syndrome in the lungs, and even complicated clinical manifestations with variable multi-organ injuries. Gao et al. revealed wide distribution and active replication of SARSCoV-2 in multi-organs of rhesus macaques post infection for 7 days and further profiled dynamic transcriptomic landscape of multi-organs. The cover image showed multiple organs infected with SARS-CoV-2 and hyperinflammatory state of brain. The SARS-CoV-2-induced elevated expression of receptor NRP1 caused an active inflammatory immune response in cerebral cortex and close signaling transmission across tissues, and eventually led to viral encephalitis.

Recollections
The early days of structural biology at the Beijing Institute of Biophysics: In memory of Professor Zhengjiong Lin (1935–2022)
Jia-huai Wang
2022, 13(12): 869-872. doi: 10.1007/s13238-022-00916-4
[Abstract](446) [PDF 760KB](90)
Abstract:
A world renowned psychophysiologist: Kaoliang Chow
Lei Zhang, Lijun Wang, Benyu Guo, Yanyan Qian, Qingming Liu
2022, 13(12): 873-876. doi: 10.1007/s13238-020-00797-5
[Abstract](384) [PDF 590KB](27)
Abstract:
Review
Metabolic reprogramming and epigenetic modifications on the path to cancer
Linchong Sun, Huafeng Zhang, Ping Gao
2022, 13(12): 877-919. doi: 10.1007/s13238-021-00846-7
[Abstract](1218) [PDF 1773KB](194)
Abstract:
Metabolic rewiring and epigenetic remodeling, which are closely linked and reciprocally regulate each other, are among the well-known cancer hallmarks. Recent evidence suggests that many metabolites serve as substrates or cofactors of chromatin-modifying enzymes as a consequence of the translocation or spatial regionalization of enzymes or metabolites. Various metabolic alterations and epigenetic modifications also reportedly drive immune escape or impede immunosurveillance within certain contexts, playing important roles in tumor progression. In this review, we focus on how metabolic reprogramming of tumor cells and immune cells reshapes epigenetic alterations, in particular the acetylation and methylation of histone proteins and DNA. We also discuss other eminent metabolic modifications such as, succinylation, hydroxybutyrylation, and lactylation, and update the current advances in metabolism- and epigenetic modification-based therapeutic prospects in cancer.
Research Articles
Differential transcriptomic landscapes of multiple organs from SARS-CoV-2 early infected rhesus macaques
Chun-Chun Gao, Man Li, Wei Deng, Chun-Hui Ma, Yu-Sheng Chen, Yong-Qiao Sun, Tingfu Du, Qian-Lan Liu, Wen-Jie Li, Bing Zhang, Lihong Sun, Si-Meng Liu, Fengli Li, Feifei Qi, Yajin Qu, Xinyang Ge, Jiangning Liu, Peng Wang, Yamei Niu, Zhiyong Liang, Yong-Liang Zhao, Bo Huang, Xiao-Zhong Peng, Ying Yang, Chuan Qin, Wei-Min Tong, Yun-Gui Yang
2022, 13(12): 920-939. doi: 10.1007/s13238-022-00915-5
[Abstract](1050) [PDF 17522KB](279)
Abstract:
SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Based on our findings, neuropilin 1 (NRP1), a receptor of SARS-CoV-2, was significantly elevated in cerebral cortex post infection, accompanied by active immune response releasing inflammatory factors and signal transmission among tissues, which enhanced infection of the central nervous system (CNS) in a positive feedback way, leading to viral encephalitis. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.
Targeting papain-like protease for broad-spectrum coronavirus inhibition
Shuofeng Yuan, Xiaopan Gao, Kaiming Tang, Jian-Piao Cai, Menglong Hu, Peng Luo, Lei Wen, Zi-Wei Ye, Cuiting Luo, Jessica Oi-Ling Tsang, Chris Chun-Yiu Chan, Yaoqiang Huang, Jianli Cao, Ronghui Liang, Zhenzhi Qin, Bo Qin, Feifei Yin, Hin Chu, Dong-Yan Jin, Ren Sun, Jasper Fuk-Woo Chan, Sheng Cui, Kwok-Yung Yuen
2022, 13(12): 940-953. doi: 10.1007/s13238-022-00909-3
[Abstract](937) [PDF 2267KB](234)
Abstract:
The emergence of SARS-CoV-2 variants of concern and repeated outbreaks of coronavirus epidemics in the past two decades emphasize the need for next-generation pan-coronaviral therapeutics. Drugging the multi-functional papain-like protease (PLpro) domain of the viral nsp3 holds promise. However, none of the known coronavirus PLpro inhibitors has been shown to be in vivo active. Herein, we screened a structurally diverse library of 50,080 compounds for potential coronavirus PLpro inhibitors and identified a noncovalent lead inhibitor F0213 that has broad-spectrum anti-coronaviral activity, including against the Sarbecoviruses (SARS-CoV-1 and SARS-CoV-2), Merbecovirus (MERS-CoV), as well as the Alphacoronavirus (hCoV-229E and hCoV-OC43). Importantly, F0213 confers protection in both SARS-CoV-2-infected hamsters and MERS-CoV-infected human DPP4-knockin mice. F0213 possesses a dual therapeutic functionality that suppresses coronavirus replication via blocking viral polyprotein cleavage, as well as promoting antiviral immunity by antagonizing the PLpro deubiquitinase activity. Despite the significant difference of substrate recognition, mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue, whereas an allosteric inhibitor of MERS-PLpro interacting with its 271E position. Our proof-of-concept findings demonstrated that PLpro is a valid target for the development of broad-spectrum anti-coronavirus agents. The orally administered F0213 may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and future coronavirus outbreaks.
Letter
FTO stabilizes MIS12 and counteracts senescence
Sheng Zhang, Zeming Wu, Yue Shi, Si Wang, Jie Ren, Zihui Yu, Daoyuan Huang, Kaowen Yan, Yifang He, Xiaoqian Liu, Qianzhao Ji, Beibei Liu, Zunpeng Liu, Jing Qu, Guang-Hui Liu, Weimin Ci, Xiaoqun Wang, Weiqi Zhang
2022, 13(12): 954-960. doi: 10.1007/s13238-022-00914-6
[Abstract](1042) [PDF 1504KB](288)
Abstract:
Correction
Correction to: mTORC2/RICTOR exerts differential levels of metabolic control in human embryonic, mesenchymal and neural stem cells
Qun Chu, Feifei Liu, Yifang He, Xiaoyu Jiang, Yusheng Cai, Zeming Wu, Kaowen Yan, Lingling Geng, Yichen Zhang, Huyi Feng, Kaixin Zhou, Si Wang, Weiqi Zhang, Guang-Hui Liu, Shuai Ma, Jing Qu, Moshi Song
2022, 13(12): 961-961. doi: 10.1007/s13238-022-00917-3
[Abstract](188) [PDF 130KB](16)
Abstract:
Correction to: Gonadal mosaicism mediated female-biased gender control in mice
Meizhu Bai, Dan Liang, Yan Cheng, Guolong Liu, Qiudao Wang, Jinsong Li, Yuxuan Wu
2022, 13(12): 962-962. doi: 10.1007/s13238-022-00918-2
[Abstract](164) [PDF 101KB](5)
Abstract:

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