Bioactive compounds from Huashi Baidu decoction possess both antiviral and anti-inflammatory effects against COVID-19
Haiyu Xu, Shufen Li, Jiayuan Liu, Jinlong Cheng, Liping Kang, Weijie Li, Yute Zhong, Chaofa Wei, Lifeng Fu, Jianxun Qi, Yulan Zhang, Miaomiao You, Zhenxing Zhou, Chongtao Zhang, Haixia Su, Sheng Yao, Zhaoyin Zhou, Yulong Shi, Ran Deng, Qi Lv, Fengdi Li, Feifei Qi, Jie Chen, Siqin Zhang, Xiaojing Ma, Zhijian Xu, Shao Li, Yechun Xu, Ke Peng, Yi Shi, Hualiang Jiang, George F Gao, Luqi Huang
Proceedings of the National Academy of Sciences, doi:10.1073/pnas.2301775120
Significance Huashi Baidu decoction (Q-14), a famous traditional Chinese medicine decoction for COVID-19, has good effects on SARS-CoV-2 RNA clearance, promoting lung lesion opacity absorption, reducing inflammation, and ameliorating flu-like symptoms based on a series of clinical trials, having potent antiviral and antiinflammatory effects. However, due to the lack of systematic and in-depth research, little significant progress has been made in the study of TCMT-NDRD of HBF for COVID-19 management. Therefore, the aim of the current study was to identify key antiviral and anti-inflammatory bioactive compounds from HBF based on an integrative pharmacological strategy. These findings will greatly stimulate the traditional Chinese medicine theory-driven natural drug discovery against COVID-19 and promote the modern research of Chinese medicine.
References
Adams, Grosse-Kunstleve, Li, Ioerger, Terwilliger, PHENIX: Building new software for automated crystallographic structure determination, Acta Crystallogr. D
Al-Kuraishy, Sequential doxycycline and colchicine combination therapy in Covid-19: The salutary effects, Pulm. Pharmacol. Ther
Baell, Walters, Chemistry: Chemical con artists foil drug discovery, Nature
Bai, Structural basis for the inhibition of the SARS-CoV-2 main protease by the anti-HCV drug narlaprevir, Signal Transduct. Targeted Ther
Bailey, The ccp4 suite -programs for protein crystallography, Acta Crystallogr. Sect. D
Bernal, Molnupiravir for oral treatment of Covid-19 in nonhospitalized patients, N. Engl. J. Med
Chen, 5-hydroxymethylcytosine signatures in circulating cell-free DNA as early warning biomarkers for COVID-19 progression and myocardial injury, Front. Cell Dev. Biol
Emsley, Cowtan, Coot: Model-building tools for molecular graphics, Acta Crystallogr. D
Feng, Li, Zhang, Yin, Li, Crystal structure of SARS-CoV 3C-like protease with baicalein, Biochem. Biophys. Res. Commun
Fu, Mechanism of microbial metabolite leupeptin in the treatment of COVID-19 by traditional Chinese medicine herbs, mBio
Gordon, Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency, J. Biol. Chem
Gottlieb, Effect of bamlanivimab as monotherapy or in combination with etesevimab on viral load in patients with mild to moderate COVID-19: A randomized clinical trial, Jama
Huang, Clinical features of patients infected with 2019 novel coronavirus in Wuhan. China, Lancet
Huang, Traditional Chinese medicine (TCM) in the treatment of COVID-19 and other viral infections: Efficacies and mechanisms, Pharmacol. Therapeut
Ingolfsson, Phytochemicals perturb membranes and promiscuously alter protein function, ACS Chem. Biol
Koes, Baumgartner, Camacho, Lessons learned in empirical scoring with smina from the CSAR 2011 benchmarking exercise, J. Chem. Inf. Model
Li, Potential treatment of COVID-19 with traditional chinese medicine: What herbs can help win the battle with SARS-CoV-2?, Engineering
Li, SARS-CoV-2 Z-RNA activates the ZBP1-RIPK3 pathway to promote virus-induced inflammatory responses, Cell Res
Li, SARS-CoV-2 triggers inflammatory responses and cell death through caspase-8 activation, Signal Transduct. Target. Ther
Li, SFTSV infection induces BAK/BAX-dependent Mitochondrial DNA release to trigger NLRP3 inflammasome activation, Cell Rep
Liu, A novel STING agonist-adjuvanted pan-sarbecovirus vaccine elicits potent and durable neutralizing antibody and T cell responses in mice, rabbits and NHPs, Cell Res
Liu, Combination of Hua Shi Bai Du granule (Q-14) and standard care in the treatment of patients with coronavirus disease 2019 (COVID-19): A single-center, open-label, randomized controlled trial, Phytomedicine
Liu, He, Huang, Wei, Zhu, Severe fever with thrombocytopenia syndrome, an emerging tick-borne zoonosis, Lancet. Infect. Dis
Liu, Herb-drug interactions involving drug metabolizing enzymes and transporters, Curr. Drug. Metab
Liu, SFTSV infection induced interleukin-1β secretion through NLRP3 inflammasome activation, Front. Immunol
Lyu, Traditional Chinese medicine in COVID-19, Acta Pharm. Sin. B
Mangalmurti, Hunter, Cytokine storms: Understanding COVID-19, Immunity
Maurice, Advances in targeting cyclic nucleotide phosphodiesterases, Nat. Rev. Drug. Discov
Minor, Cymborowski, Otwinowski, Chruszcz, Hkl-, The integration of data reduction and structure solution-from diffraction images to an initial model in minutes, Acta Crystallogr. D
Najjar-Debbiny, Effectiveness of paxlovid in reducing severe COVID-19 and mortality in high risk patients, Clin. Infect. Dis
Niu, Network pharmacology analysis to identify phytochemicals in traditional Chinese medicines that may regulate ACE2 for the treatment of COVID-19, Evid. Based Complement. Alternat. Med
Niu, Network pharmacology for the identification of phytochemicals in traditional Chinese medicine for COVID-19 that may regulate interleukin-6, Biosci. Rep
Peng, Structural and biochemical characterization of the nsp12-nsp7-nsp8 core polymerase complex from SARS-CoV-2, Cell Rep
Runfeng, Lianhuaqingwen exerts anti-viral and anti-inflammatory activity against novel coronavirus (SARS-CoV-2), Pharmacol. Res
Saravolatz, Depcinski, Sharma, Molnupiravir and nirmatrelvir-ritonavir: Oral Coronavirus disease 2019 antiviral drugs, Clin. Infect. Dis
Sen, Identification of potential edible mushroom as SARS-CoV-2 main protease inhibitor using rational drug designing approach, Sci. Rep
Shankar-Hari, Association between administration of IL-6 antagonists and mortality among patients hospitalized for COVID-19: A meta-analysis, Jama
Shi, D3Targets-2019-nCoV: A webserver for predicting drug targets and for multi-target and multi-site based virtual screening against COVID-19, Acta Pharm. Sin. B
Shi, Efficacy and safety of Chinese herbal medicine versus Lopinavir-Ritonavir in adult patients with coronavirus disease 2019: A non-randomized controlled trial, Phytomedicine
Su, Identification of pyrogallol as a warhead in design of covalent inhibitors for the SARS-CoV-2 3CL protease, Nat. Commun
Tan, A novel coronavirus genome identified in a cluster of pneumonia cases -Wuhan, China 2019-2020, China CDC weekly
Trott, Olson, AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading, J. Comput. Chem
Tu, The discovery of artemisinin (qinghaosu) and gifts from Chinese medicine, Nat. Med
Wang, Artemisinin, the magic drug discovered from traditional Chinese medicine, Engineering
Wang, Deciphering the active compounds and mechanisms of HSBDF for treating ALI via integrating chemical bioinformatics analysis, Front. Pharmacol
Wang, Upgrade of macromolecular crystallography beamline BL17U1at SSRF, Nucl Sci. Tech
Wang, Zhang, Zhan, Gao, Screening out anti-inflammatory or anti-viral targets in Xuanfei Baidu Tang through a new technique of reverse finding target, Bioorg. Chem
Wegesser, Coppi, Harper, Paris, Minocherhomji, Nonclinical genotoxicity and carcinogenicity profile of apremilast, an oral selective inhibitor of PDE4, Regul. Toxicol. Pharmacol. RTP
Wei, Chemical profiling of Huashi Baidu prescription, an effective anti-COVID-19 TCM formula, by UPLC-Q-TOF/MS, Chinese J. Nat Med
Xiong, The effect of Huashibaidu formula on the blood oxygen saturation status of severe COVID-19: A retrospective cohort study, Phytomed. Int. J. Phytothera. Phytopharmacol
Xiong, Wang, Du, Ai, Efficacy of herbal medicine (Xuanfei Baidu decoction) combined with conventional drug in treating COVID-19: A pilot randomized clinical trial, Integra. Med. Res
Xu, A comprehensive review of integrative pharmacology-based investigation: A paradigm shift in traditional Chinese medicine, Acta Pharm. Sin. B
Xu, ETCM: An encyclopaedia of traditional Chinese medicine, Nucleic Acids Res
Yang, Mice transgenic for human angiotensin-converting enzyme 2 provide a model for SARS coronavirus infection, Comparat. Med
Yu, Ju, Ding, A nucleocapsid-based transcomplementation cell culture system of SARS-CoV-2 to recapitulate the complete viral life cycle, Bio Protocol
Zebda, Paller, Phosphodiesterase 4 inhibitors, J. Am. Acad. Dermatol
Zhang, Association between use of Qingfei Paidu Tang and mortality in hospitalized patients with COVID-19: A national retrospective registry study, Phytomedicine
Zhang, Dong, Li, Chen, Xu, Structure-aided identification and optimization of tetrahydro-isoquinolines as novel PDE4 inhibitors leading to discovery of an effective anti-psoriasis agent, J. Med. Chem
Zhang, Ibrahim, Gillette, Bollag, Phosphodiesterase-4 as a potential drug target, Expert. Opin. Ther. Targets
Zhang, Li, Zhang, Li, Liu, Design, synthesis, and biological evaluation of tetrahydroisoquinolines derivatives as novel, selective PDE4 inhibitors for antipsoriasis treatment, Eur. J. Med. Chem
Zhang, SoFDA: An integrated web platform from syndrome ontology to network-based evaluation of disease-syndrome-formula associations for precision medicine, Sci. Bull
Zhao, Chinese medicine formula huashibaidu granule early treatment for mild COVID-19 patients: An unblinded, cluster-randomized clinical trial, Front. Med
Zhou, A pneumonia outbreak associated with a new coronavirus of probable bat origin, Nature
Zhu, A novel coronavirus from patients with pneumonia in China, N. Engl. J. Med
Zhu, Analyzing the potential therapeutic mechanism of Huashi Baidu Decoction on severe COVID-19 through integrating network pharmacological methods, J. Tradit. Complement. Med
Zumla, Hui, Perlman, Middle east respiratory syndrome, Lancet
{ 'indexed': {'date-parts': [[2023, 4, 25]], 'date-time': '2023-04-25T04:35:47Z', 'timestamp': 1682397347666},
'reference-count': 0,
'publisher': 'Proceedings of the National Academy of Sciences',
'issue': '18',
'license': [ { 'start': { 'date-parts': [[2023, 4, 24]],
'date-time': '2023-04-24T00:00:00Z',
'timestamp': 1682294400000},
'content-version': 'vor',
'delay-in-days': 0,
'URL': 'https://creativecommons.org/licenses/by-nc-nd/4.0/'}],
'funder': [ { 'DOI': '10.13039/501100001809',
'name': 'National Natural Science Foundation of China',
'doi-asserted-by': 'publisher',
'award': ['81830111']},
{ 'name': 'Establishment of Sino-Austria "Belt and Road" Joint Laboratory on '
'Traditional Chinese Medicine for Severe Infectious Diseases and Joint Research',
'award': ['2020YFE0205100']},
{ 'name': 'The ability establishment of sustainable use for valuablee Chinese Medicine '
'Resources',
'award': ['2060302']}],
'content-domain': {'domain': ['www.pnas.org'], 'crossmark-restriction': True},
'published-print': {'date-parts': [[2023, 5, 2]]},
'abstract': '<jats:p>\n'
' The coronavirus disease 2019 (COVID-19) pandemic is an ongoing global health '
'concern, and effective antiviral reagents are urgently needed. Traditional Chinese medicine '
'theory-driven natural drug research and development (TCMT-NDRD) is a feasible method to '
'address this issue as the traditional Chinese medicine formulae have been shown effective in '
'the treatment of COVID-19. Huashi Baidu decoction (Q-14) is a clinically approved formula for '
'COVID-19 therapy with antiviral and anti-inflammatory effects. Here, an integrative '
'pharmacological strategy was applied to identify the antiviral and anti-inflammatory '
'bioactive compounds from Q-14. Overall, a total of 343 chemical compounds were initially '
'characterized, and 60 prototype compounds in Q-14 were subsequently traced in plasma using '
'ultrahigh-performance liquid chromatography with quadrupole time-of-flight mass spectrometry. '
'Among the 60 compounds, six compounds (magnolol, glycyrrhisoflavone, licoisoflavone A, '
'emodin, echinatin, and quercetin) were identified showing a dose-dependent inhibition effect '
'on the SARS-CoV-2 infection, including two inhibitors (echinatin and quercetin) of the main '
'protease (M\n'
' <jats:sup>pro</jats:sup>\n'
' ), as well as two inhibitors (glycyrrhisoflavone and licoisoflavone A) of the '
'RNA-dependent RNA polymerase (RdRp). Meanwhile, three anti-inflammatory components, including '
'licochalcone B, echinatin, and glycyrrhisoflavone, were identified in a SARS-CoV-2-infected '
'inflammatory cell model. In addition, glycyrrhisoflavone and licoisoflavone A also displayed '
'strong inhibitory activities against cAMP-specific 3′,5′-cyclic phosphodiesterase 4 (PDE4). '
'Crystal structures of PDE4 in complex with glycyrrhisoflavone or licoisoflavone A were '
'determined at resolutions of 1.54\xa0Å and 1.65\xa0Å, respectively, and both compounds bind '
'in the active site of PDE4 with similar interactions. These findings will greatly stimulate '
'the study of TCMT-NDRD against COVID-19.\n'
' </jats:p>',
'DOI': '10.1073/pnas.2301775120',
'type': 'journal-article',
'created': {'date-parts': [[2023, 4, 24]], 'date-time': '2023-04-24T19:12:52Z', 'timestamp': 1682363572000},
'update-policy': 'http://dx.doi.org/10.1073/pnas.cm10313',
'source': 'Crossref',
'is-referenced-by-count': 0,
'title': 'Bioactive compounds from Huashi Baidu decoction possess both antiviral and anti-inflammatory '
'effects against COVID-19',
'prefix': '10.1073',
'volume': '120',
'author': [ { 'given': 'Haiyu',
'family': 'Xu',
'sequence': 'first',
'affiliation': [ { 'name': 'Institute of Chinese Materia Medica, Academy of Chinese Medical '
'Sciences, Beijing 100700, China'}]},
{ 'given': 'Shufen',
'family': 'Li',
'sequence': 'additional',
'affiliation': [ { 'name': 'State Key Laboratory of Virology, Center for Antiviral Research, '
'Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan '
'430207, China'}]},
{ 'ORCID': 'http://orcid.org/0000-0003-4062-5278',
'authenticated-orcid': False,
'given': 'Jiayuan',
'family': 'Liu',
'sequence': 'additional',
'affiliation': [ { 'name': 'State Key Laboratory of Drug Research, Shanghai Institute of '
'Materia Medica, Chinese Academy of Sciences, Shanghai 201203, '
'China'}]},
{ 'given': 'Jinlong',
'family': 'Cheng',
'sequence': 'additional',
'affiliation': [ { 'name': 'Chinese Academy of Sciences (CAS) Key Laboratory of Pathogen '
'Microbiology and Immunology, Institute of Microbiology, Chinese '
'Academy of Sciences, Beijing 100101, China'}]},
{ 'given': 'Liping',
'family': 'Kang',
'sequence': 'additional',
'affiliation': [ { 'name': 'State Key Laboratory of Dao-di Herbs, National Resource Center '
'for Chinese Materia Medica, China Academy of Chinese Medical '
'Sciences, Beijing 100700, China'}]},
{ 'given': 'Weijie',
'family': 'Li',
'sequence': 'additional',
'affiliation': [ { 'name': 'Institute of Chinese Materia Medica, Academy of Chinese Medical '
'Sciences, Beijing 100700, China'}]},
{ 'given': 'Yute',
'family': 'Zhong',
'sequence': 'additional',
'affiliation': [ { 'name': 'Institute of Chinese Materia Medica, Academy of Chinese Medical '
'Sciences, Beijing 100700, China'}]},
{ 'given': 'Chaofa',
'family': 'Wei',
'sequence': 'additional',
'affiliation': [ { 'name': 'State Key Laboratory of Dao-di Herbs, National Resource Center '
'for Chinese Materia Medica, China Academy of Chinese Medical '
'Sciences, Beijing 100700, China'}]},
{ 'given': 'Lifeng',
'family': 'Fu',
'sequence': 'additional',
'affiliation': [ { 'name': 'Chinese Academy of Sciences (CAS) Key Laboratory of Pathogen '
'Microbiology and Immunology, Institute of Microbiology, Chinese '
'Academy of Sciences, Beijing 100101, China'}]},
{ 'ORCID': 'http://orcid.org/0000-0002-9358-4732',
'authenticated-orcid': False,
'given': 'Jianxun',
'family': 'Qi',
'sequence': 'additional',
'affiliation': [ { 'name': 'Chinese Academy of Sciences (CAS) Key Laboratory of Pathogen '
'Microbiology and Immunology, Institute of Microbiology, Chinese '
'Academy of Sciences, Beijing 100101, China'},
{'name': 'Beijing Life Science Academy, Beijing 102209, China'}]},
{ 'given': 'Yulan',
'family': 'Zhang',
'sequence': 'additional',
'affiliation': [ { 'name': 'State Key Laboratory of Virology, Center for Antiviral Research, '
'Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan '
'430207, China'}]},
{ 'given': 'Miaomiao',
'family': 'You',
'sequence': 'additional',
'affiliation': [ { 'name': 'State Key Laboratory of Virology, Center for Antiviral Research, '
'Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan '
'430207, China'}]},
{ 'given': 'Zhenxing',
'family': 'Zhou',
'sequence': 'additional',
'affiliation': [ { 'name': 'State Key Laboratory of Virology, Center for Antiviral Research, '
'Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan '
'430207, China'}]},
{ 'given': 'Chongtao',
'family': 'Zhang',
'sequence': 'additional',
'affiliation': [ { 'name': 'State Key Laboratory of Virology, Center for Antiviral Research, '
'Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan '
'430207, China'}]},
{ 'given': 'Haixia',
'family': 'Su',
'sequence': 'additional',
'affiliation': [ { 'name': 'State Key Laboratory of Drug Research, Shanghai Institute of '
'Materia Medica, Chinese Academy of Sciences, Shanghai 201203, '
'China'}]},
{ 'given': 'Sheng',
'family': 'Yao',
'sequence': 'additional',
'affiliation': [ { 'name': 'State Key Laboratory of Drug Research, Shanghai Institute of '
'Materia Medica, Chinese Academy of Sciences, Shanghai 201203, '
'China'}]},
{ 'given': 'Zhaoyin',
'family': 'Zhou',
'sequence': 'additional',
'affiliation': [ { 'name': 'State Key Laboratory of Drug Research, Shanghai Institute of '
'Materia Medica, Chinese Academy of Sciences, Shanghai 201203, '
'China'}]},
{ 'given': 'Yulong',
'family': 'Shi',
'sequence': 'additional',
'affiliation': [ { 'name': 'State Key Laboratory of Drug Research, Shanghai Institute of '
'Materia Medica, Chinese Academy of Sciences, Shanghai 201203, '
'China'}]},
{ 'given': 'Ran',
'family': 'Deng',
'sequence': 'additional',
'affiliation': [ { 'name': 'Beijing Key Laboratory for Animal Models of Emerging and '
'Reemerging Infectious Diseases, Key Laboratory of Comparative '
'Medicine for Human Diseases of the National Health Commission, '
'Institute of Laboratory Animal Sciences, Chinese Academy of '
'Medical Sciences & Peking Union Medical College, Beijing '
'100021, China'}]},
{ 'given': 'Qi',
'family': 'Lv',
'sequence': 'additional',
'affiliation': [ { 'name': 'Beijing Key Laboratory for Animal Models of Emerging and '
'Reemerging Infectious Diseases, Key Laboratory of Comparative '
'Medicine for Human Diseases of the National Health Commission, '
'Institute of Laboratory Animal Sciences, Chinese Academy of '
'Medical Sciences & Peking Union Medical College, Beijing '
'100021, China'}]},
{ 'given': 'Fengdi',
'family': 'Li',
'sequence': 'additional',
'affiliation': [ { 'name': 'Beijing Key Laboratory for Animal Models of Emerging and '
'Reemerging Infectious Diseases, Key Laboratory of Comparative '
'Medicine for Human Diseases of the National Health Commission, '
'Institute of Laboratory Animal Sciences, Chinese Academy of '
'Medical Sciences & Peking Union Medical College, Beijing '
'100021, China'}]},
{ 'given': 'Feifei',
'family': 'Qi',
'sequence': 'additional',
'affiliation': [ { 'name': 'Beijing Key Laboratory for Animal Models of Emerging and '
'Reemerging Infectious Diseases, Key Laboratory of Comparative '
'Medicine for Human Diseases of the National Health Commission, '
'Institute of Laboratory Animal Sciences, Chinese Academy of '
'Medical Sciences & Peking Union Medical College, Beijing '
'100021, China'}]},
{ 'given': 'Jie',
'family': 'Chen',
'sequence': 'additional',
'affiliation': [ { 'name': 'Institute of Chinese Materia Medica, Academy of Chinese Medical '
'Sciences, Beijing 100700, China'}]},
{ 'given': 'Siqin',
'family': 'Zhang',
'sequence': 'additional',
'affiliation': [ { 'name': 'Institute for Traditional Chinese Medicine-X, Ministry of '
'Education Key Laboratory of Bioinformatics/Bioinformatics '
'Division, Beijing National Research Center for Information '
'Science and Technology, Department of Automation, Tsinghua '
'University, Beijing 100084, China'}]},
{ 'given': 'Xiaojing',
'family': 'Ma',
'sequence': 'additional',
'affiliation': [ { 'name': 'State Key Laboratory of Dao-di Herbs, National Resource Center '
'for Chinese Materia Medica, China Academy of Chinese Medical '
'Sciences, Beijing 100700, China'}]},
{ 'given': 'Zhijian',
'family': 'Xu',
'sequence': 'additional',
'affiliation': [ { 'name': 'State Key Laboratory of Drug Research, Shanghai Institute of '
'Materia Medica, Chinese Academy of Sciences, Shanghai 201203, '
'China'}]},
{ 'given': 'Shao',
'family': 'Li',
'sequence': 'additional',
'affiliation': [ { 'name': 'Institute for Traditional Chinese Medicine-X, Ministry of '
'Education Key Laboratory of Bioinformatics/Bioinformatics '
'Division, Beijing National Research Center for Information '
'Science and Technology, Department of Automation, Tsinghua '
'University, Beijing 100084, China'}]},
{ 'given': 'Yechun',
'family': 'Xu',
'sequence': 'additional',
'affiliation': [ { 'name': 'State Key Laboratory of Drug Research, Shanghai Institute of '
'Materia Medica, Chinese Academy of Sciences, Shanghai 201203, '
'China'}]},
{ 'given': 'Ke',
'family': 'Peng',
'sequence': 'additional',
'affiliation': [ { 'name': 'State Key Laboratory of Virology, Center for Antiviral Research, '
'Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan '
'430207, China'}]},
{ 'given': 'Yi',
'family': 'Shi',
'sequence': 'additional',
'affiliation': [ { 'name': 'Chinese Academy of Sciences (CAS) Key Laboratory of Pathogen '
'Microbiology and Immunology, Institute of Microbiology, Chinese '
'Academy of Sciences, Beijing 100101, China'},
{'name': 'Beijing Life Science Academy, Beijing 102209, China'}]},
{ 'given': 'Hualiang',
'family': 'Jiang',
'sequence': 'additional',
'affiliation': [ { 'name': 'State Key Laboratory of Drug Research, Shanghai Institute of '
'Materia Medica, Chinese Academy of Sciences, Shanghai 201203, '
'China'}]},
{ 'ORCID': 'http://orcid.org/0000-0002-3869-615X',
'authenticated-orcid': False,
'given': 'George F.',
'family': 'Gao',
'sequence': 'additional',
'affiliation': [ { 'name': 'Chinese Academy of Sciences (CAS) Key Laboratory of Pathogen '
'Microbiology and Immunology, Institute of Microbiology, Chinese '
'Academy of Sciences, Beijing 100101, China'},
{'name': 'Beijing Life Science Academy, Beijing 102209, China'}]},
{ 'given': 'Luqi',
'family': 'Huang',
'sequence': 'additional',
'affiliation': [ { 'name': 'State Key Laboratory of Dao-di Herbs, National Resource Center '
'for Chinese Materia Medica, China Academy of Chinese Medical '
'Sciences, Beijing 100700, China'}]}],
'member': '341',
'published-online': {'date-parts': [[2023, 4, 24]]},
'container-title': 'Proceedings of the National Academy of Sciences',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'https://pnas.org/doi/pdf/10.1073/pnas.2301775120',
'content-type': 'unspecified',
'content-version': 'vor',
'intended-application': 'similarity-checking'}],
'deposited': { 'date-parts': [[2023, 4, 24]],
'date-time': '2023-04-24T19:15:31Z',
'timestamp': 1682363731000},
'score': 1,
'resource': {'primary': {'URL': 'https://pnas.org/doi/10.1073/pnas.2301775120'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2023, 4, 24]]},
'references-count': 0,
'journal-issue': {'issue': '18', 'published-print': {'date-parts': [[2023, 5, 2]]}},
'alternative-id': ['10.1073/pnas.2301775120'],
'URL': 'http://dx.doi.org/10.1073/pnas.2301775120',
'relation': {},
'ISSN': ['0027-8424', '1091-6490'],
'subject': ['Multidisciplinary'],
'container-title-short': 'Proc. Natl. Acad. Sci. U.S.A.',
'published': {'date-parts': [[2023, 4, 24]]},
'assertion': [ { 'value': '2023-02-02',
'order': 0,
'name': 'received',
'label': 'Received',
'group': {'name': 'publication_history', 'label': 'Publication History'}},
{ 'value': '2023-03-14',
'order': 1,
'name': 'accepted',
'label': 'Accepted',
'group': {'name': 'publication_history', 'label': 'Publication History'}},
{ 'value': '2023-04-24',
'order': 2,
'name': 'published',
'label': 'Published',
'group': {'name': 'publication_history', 'label': 'Publication History'}}]}
