2021-10-13

Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland, United States of America.; St. Michael's Hospital, University of Toronto, Toronto, Canada.; St. Michael's Hospital, University of Toronto, Toronto, Canada.; ICES, Toronto, Canada; Department of Family and Community Medicine, Faculty of Medicine, University of Toronto, Toronto, Canada; Public Health Ontario, Toronto, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, Canada; University Health Network, Toronto, ON.; St. Michael's Hospital, University of Toronto, Toronto, Canada.; ICES, Toronto, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada; Public Health Ontario, Toronto, Canada.; Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.; Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland, United States of America.; St. Michael's Hospital, University of Toronto, Toronto, Canada; Division of Infectious Diseases, Department of Medicine, University of Toronto, Toronto, Canada. Electronic address: sharmistha.mishra@utoronto.ca.

Shelter-in-place mandates and closure of nonessential businesses have been central to COVID19 response strategies including in Toronto, Canada. Approximately half of the working population in Canada are employed in occupations that do not allow for remote work suggesting potentially limited impact of some of the strategies proposed to mitigate COVID-19 acquisition and onward transmission risks and associated morbidity and mortality. We compared per-capita rates of COVID-19 cases and deaths from January 23, 2020 to January 24, 2021, across neighborhoods in Toronto by proportion of the population working in essential services. We used person-level data on laboratory-confirmed COVID-19 community cases and deaths, and census data for neighborhood-level attributes. Cumulative per-capita rates of COVID-19 cases and deaths were 3.3-fold and 2.5-fold higher, respectively, in neighborhoods with the highest versus lowest concentration of essential workers. Findings suggest that the population

2021-02-21

Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.; Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of Innate Immunity and Chronic Disease, Division of Life Sciences and Medicine, School of Basic Medical Sciences, University of Science and Technology of China, Hefei, Anhui, China.; Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of Innate Immunity and Chronic Disease, Division of Life Sciences and Medicine, School of Basic Medical Sciences, University of Science and Technology of China, Hefei, Anhui, China.; Division of Life Sciences and Medicine, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, China.; Division of Life Sciences and Medicine, Department of Infectious Diseases, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, China.; Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of Innate Immunity and Chronic Disease, Division of Life Sciences and Medicine, School of Basic Medical Sciences, University of Science and Technology of China, Hefei, Anhui, China.; Anhui Center for Disease Control and Prevention (Anhui CDC), Hefei, Anhui, China.; Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of Innate Immunity and Chronic Disease, Division of Life Sciences and Medicine, School of Basic Medical Sciences, University of Science and Technology of China, Hefei, Anhui, China.; Kangrun Biotech LTD, Guangzhou, Guangdong, China.; Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.; Division of Life Sciences and Medicine, Department of Infectious Diseases, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, China. ygao87@ustc.edu.cn.; Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China. jint@ustc.edu.cn.; Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of Innate Immunity and Chronic Disease, Division of Life Sciences and Medicine, School of Basic Medical Sciences, University of Science and Technology of China, Hefei, Anhui, China. jint@ustc.edu.cn.; CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Science, Shanghai, China. jint@ustc.edu.cn.

2021-09-28

The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.; The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.; Department of Microbiology, Anhui Provincial Center for Disease Control and Prevention, Hefei, China.; The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.; The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.; The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.; Department of Microbiology, Anhui Provincial Center for Disease Control and Prevention, Hefei, China.; The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.; The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.; The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.; The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.; Division of Life Sciences and Medicine, Laboratory of Structural Immunology, University of Science and Technology of China (USTC), Hefei, China.; Division of Life Sciences and Medicine, Laboratory of Structural Immunology, University of Science and Technology of China (USTC), Hefei, China.; The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.; The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

The mutants resulted from the ongoing SARS-CoV-2 epidemic have showed resistance to antibody neutralization and vaccine-induced immune response. The present study isolated and identified two novel SARS-CoV-2 neutralizing antibodies (nAbs) from convalescent COVID-19 patients. These two nAbs (XG81 and XG83) were then systemically compared with nine nAbs that were reconstructed by using published data, and revealed that, even though these two nAbs shared targeting epitopes on spike protein, they were different from any of the nine nAbs. Compared with XG81, XG83 exhibited a higher RBD binding affinity and neutralization potency against wild-typed pseudovirus, variant pseudoviruses with mutated spike proteins, such as D614G, E484Q, and A475V, as well as the authentic SARS-CoV-2 virus. To explore potential broadly neutralizing antibodies, heavy and light chains from all 18 nAbs (16 published nAbs, XG81 and XG83) were cross-recombined, and some of the functional antibodies were screened and

2021-06-03

Department of Emergency and Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.; Department of Cardiology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial Cardiovascular Institute, Guangzhou, 510080, China.; Department of Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial Geriatrics Institute, Guangzhou, 510080, China.; Department of Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial Geriatrics Institute, Guangzhou, 510080, China.; Department of Emergency Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.; Department of Respiratory and Critical Care Medicine, the First People's Hospital of Shaoguan, Shaoguan, 512000, China.; Department of Emergency, the First Affiliated Hospital of Jingzhou, Jingzhou, 434000, China.; Department of Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial Geriatrics Institute, Guangzhou, 510080, China.; Department of Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial Geriatrics Institute, Guangzhou, 510080, China.; Department of Gastroenterology, the First Affiliated Hospital of Yangtze University, Jingzhou, 434000, China.; Department of Critical Care Medicine, Dongguan Eighth People's Hospital, Dongguan Children's Hospital, Dongguan, 523000, China. songxiuchan0769@163.com.; Department of Gastroenterology, the First Affiliated Hospital of Yangtze University, Jingzhou, 434000, China. zqcn@qq.com.; Department of Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial Geriatrics Institute, Guangzhou, 510080, China. hdzdoctor@139.com.

BACKGROUND: Could nutritional status serve as prognostic factors for coronavirus disease 2019 (COVID-19)? The present study evaluated the clinical and nutritional characteristics of COVID-19 patients and explored the relationship between risk for malnutrition at admission and in-hospital mortality. METHODS: A retrospective, observational study was conducted in two hospitals in Hubei, China. Confirmed cases of COVID-19 were typed as mild/moderate, severe, or critically ill. Clinical data and in-hospital death were collected. The risk for malnutrition was assessed using the geriatric nutritional risk index (GNRI), the prognostic nutritional index (PNI), and the Controlling Nutritional Status (CONUT) via objective parameters at admission. RESULTS: Two hundred ninety-five patients were enrolled, including 66 severe patients and 41 critically ill patients. Twenty-five deaths were observed, making 8.47% in the whole population and 37.88% in the critically ill subgroup. Patients had

2021-02-28

The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.; Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.; The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.; Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.; Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.; Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.; Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.; Key Laboratory for Medical and Health of the 13th Five-Year Plan, Anhui Provincial Center for Disease Control and Prevention, Hefei, China.; Key Laboratory for Medical and Health of the 13th Five-Year Plan, Anhui Provincial Center for Disease Control and Prevention, Hefei, China.; The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.; The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.; The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.; The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.; The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. maxiaoling@ustc.edu.cn.; Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. Jint@ustc.edu.cn.; The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. zhushu@ustc.edu.cn.; Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. zhushu@ustc.edu.cn.; School of Data Science, University of Science and Technology of China, Hefei, China. zhushu@ustc.edu.cn.; CAS Centre for Excellence in Cell and Molecular Biology, University of Science and Technology of China, Hefei, China. zhushu@ustc.edu.cn.

2020-03-03

grid.410745.30000 0004 1765 1045Nanjing Infectious Disease Center, the Second; Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210003 China grid.89957.3a0000 0000 9255 8984Department of Epidemiology, Center for Global; Health, School of Public Health, Nanjing Medical University, Nanjing, 211166 China grid.410745.30000 0004 1765 1045Department of Radiology, the Second Hospital of; Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210003 China grid.89957.3a0000 0000 9255 8984Department of Epidemiology, Center for Global; Health, School of Public Health, Nanjing Medical University, Nanjing, 211166 China grid.410745.30000 0004 1765 1045Nanjing Infectious Disease Center, the Second; Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210003 China grid.89957.3a0000 0000 9255 8984Department of Epidemiology, Center for Global; Health, School of Public Health, Nanjing Medical University, Nanjing, 211166 China grid.89957.3a0000 0000 9255 8984Department of Epidemiology, Center for Global; Health, School of Public Health, Nanjing Medical University, Nanjing, 211166 China grid.410745.30000 0004 1765 1045Department of Clinical Research Center, the; Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210003 China grid.89957.3a0000 0000 9255 8984Department of Maternal, Child and Adolescent; Health, School of Public Health, Nanjing Medical University, Nanjing, 211166 China grid.410745.30000 0004 1765 1045Department of Critical Medicine, the Second; Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210003 China grid.89957.3a0000 0000 9255 8984Department of Epidemiology, Center for Global; Health, School of Public Health, Nanjing Medical University, Nanjing, 211166 China grid.410745.30000 0004 1765 1045Nanjing Infectious Disease Center, the Second; Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210003 China grid.410745.30000 0004 1765 1045Nanjing Infectious Disease Center, the Second; Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210003 China grid.89957.3a0000 0000 9255 8984Department of Epidemiology, Center for Global; Health, School of Public Health, Nanjing Medical University, Nanjing, 211166 China

Previous studies have showed clinical characteristics of patients with the 2019 novel coronavirus disease (COVID-19) and the evidence of person-to-person transmission. Limited data are available for asymptomatic infections. This study aims to present the clinical characteristics of 24 cases with asymptomatic infection screened from close contacts and to show the transmission potential of asymptomatic COVID-19 virus carriers. Epidemiological investigations were conducted among all close contacts of COVID-19 patients (or suspected patients) in Nanjing, Jiangsu Province, China, from Jan 28 to Feb 9, 2020, both in clinic and in community. Asymptomatic carriers were laboratory-confirmed positive for the COVID-19 virus by testing the nucleic acid of the pharyngeal swab samples. Their clinical records, laboratory assessments, and chest CT scans were reviewed. As a result, none of the 24 asymptomatic cases presented any obvious symptoms

2020-03-03

grid.410745.30000 0004 1765 1045Nanjing Infectious Disease Center, the Second; Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210003 China grid.89957.3a0000 0000 9255 8984Department of Epidemiology, Center for Global; Health, School of Public Health, Nanjing Medical University, Nanjing, 211166 China grid.410745.30000 0004 1765 1045Department of Radiology, the Second Hospital of; Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210003 China grid.89957.3a0000 0000 9255 8984Department of Epidemiology, Center for Global; Health, School of Public Health, Nanjing Medical University, Nanjing, 211166 China grid.410745.30000 0004 1765 1045Nanjing Infectious Disease Center, the Second; Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210003 China grid.89957.3a0000 0000 9255 8984Department of Epidemiology, Center for Global; Health, School of Public Health, Nanjing Medical University, Nanjing, 211166 China grid.89957.3a0000 0000 9255 8984Department of Epidemiology, Center for Global; Health, School of Public Health, Nanjing Medical University, Nanjing, 211166 China grid.410745.30000 0004 1765 1045Department of Clinical Research Center, the; Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210003 China grid.89957.3a0000 0000 9255 8984Department of Maternal, Child and Adolescent; Health, School of Public Health, Nanjing Medical University, Nanjing, 211166 China grid.410745.30000 0004 1765 1045Department of Critical Medicine, the Second; Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210003 China grid.89957.3a0000 0000 9255 8984Department of Epidemiology, Center for Global; Health, School of Public Health, Nanjing Medical University, Nanjing, 211166 China grid.410745.30000 0004 1765 1045Nanjing Infectious Disease Center, the Second; Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210003 China grid.410745.30000 0004 1765 1045Nanjing Infectious Disease Center, the Second; Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210003 China grid.89957.3a0000 0000 9255 8984Department of Epidemiology, Center for Global; Health, School of Public Health, Nanjing Medical University, Nanjing, 211166 China

Previous studies have showed clinical characteristics of patients with the 2019 novel coronavirus disease (COVID-19) and the evidence of person-to-person transmission. Limited data are available for asymptomatic infections. This study aims to present the clinical characteristics of 24 cases with asymptomatic infection screened from close contacts and to show the transmission potential of asymptomatic COVID-19 virus carriers. Epidemiological investigations were conducted among all close contacts of COVID-19 patients (or suspected patients) in Nanjing, Jiangsu Province, China, from Jan 28 to Feb 9, 2020, both in clinic and in community. Asymptomatic carriers were laboratory-confirmed positive for the COVID-19 virus by testing the nucleic acid of the pharyngeal swab samples. Their clinical records, laboratory assessments, and chest CT scans were reviewed. As a result, none of the 24 asymptomatic cases presented any obvious symptoms

2020-02-04

Department of Psychiatry, RenMin Hospital of Wuhan University, Wuhan 430060,; China Wuhan Mental Health Center, Wuhan, China; Department of Psychiatry, First Affiliated Hospital, Zhejiang University School; of Medicine, Hangzhou, China The School of Computer Science and Technology, Huazhong University of Science and; Technology, Wuhan, China Department of Psychiatry, RenMin Hospital of Wuhan University, Wuhan 430060,; China School of Health Sciences, Wuhan University, Wuhan, China; Department of Psychiatry, RenMin Hospital of Wuhan University, Wuhan 430060,; China Department of Psychiatry, First Affiliated Hospital, Zhejiang University School; of Medicine, Hangzhou, China Department of Psychiatry, First Affiliated Hospital, Zhejiang University School; of Medicine, Hangzhou, China Department of Psychiatry, First Affiliated Hospital of Xi'an Jiaotong University,; Xi'an, China Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, ; Shanghai, China Peking University Sixth Hospital, Peking University Institute of Mental Health,; NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China Department of Psychiatry, RenMin Hospital of Wuhan University, Wuhan 430060,; China Peking University Sixth Hospital, Peking University Institute of Mental Health,; NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China Department of Psychiatry, RenMin Hospital of Wuhan University, Wuhan 430060,; China

2020-02-04

Department of Psychiatry, RenMin Hospital of Wuhan University, Wuhan 430060,; China Wuhan Mental Health Center, Wuhan, China; Department of Psychiatry, First Affiliated Hospital, Zhejiang University School; of Medicine, Hangzhou, China The School of Computer Science and Technology, Huazhong University of Science and; Technology, Wuhan, China Department of Psychiatry, RenMin Hospital of Wuhan University, Wuhan 430060,; China School of Health Sciences, Wuhan University, Wuhan, China; Department of Psychiatry, RenMin Hospital of Wuhan University, Wuhan 430060,; China Department of Psychiatry, First Affiliated Hospital, Zhejiang University School; of Medicine, Hangzhou, China Department of Psychiatry, First Affiliated Hospital, Zhejiang University School; of Medicine, Hangzhou, China Department of Psychiatry, First Affiliated Hospital of Xi'an Jiaotong University,; Xi'an, China Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, ; Shanghai, China Peking University Sixth Hospital, Peking University Institute of Mental Health,; NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China Department of Psychiatry, RenMin Hospital of Wuhan University, Wuhan 430060,; China Peking University Sixth Hospital, Peking University Institute of Mental Health,; NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China Department of Psychiatry, RenMin Hospital of Wuhan University, Wuhan 430060,; China

2021-12-14

Neutron Scattering Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, United States.; National Virtual Biotechnology Laboratory, US Department of Energy, Washington, District of Columbia 20585, United States.; National Virtual Biotechnology Laboratory, US Department of Energy, Washington, District of Columbia 20585, United States.; Center for Nanophase Materials Sciences, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, United States.; National Virtual Biotechnology Laboratory, US Department of Energy, Washington, District of Columbia 20585, United States.; Biosciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, United States.; Neutron Scattering Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, United States.; National Virtual Biotechnology Laboratory, US Department of Energy, Washington, District of Columbia 20585, United States.; National Virtual Biotechnology Laboratory, US Department of Energy, Washington, District of Columbia 20585, United States.; Biosciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, United States.; Neutron Scattering Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, United States.; National Virtual Biotechnology Laboratory, US Department of Energy, Washington, District of Columbia 20585, United States.; Neutron Scattering Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, United States.; National Virtual Biotechnology Laboratory, US Department of Energy, Washington, District of Columbia 20585, United States.; National Virtual Biotechnology Laboratory, US Department of Energy, Washington, District of Columbia 20585, United States.; Center for Nanophase Materials Sciences, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, United States.; National Virtual Biotechnology Laboratory, US Department of Energy, Washington, District of Columbia 20585, United States.; Data Science and Learning Division, Argonne National Laboratory, Lemont, Illinois 60439, United States.; Department of Computer Science, University of Chicago, Chicago, Illinois 60615, United States.; National Virtual Biotechnology Laboratory, US Department of Energy, Washington, District of Columbia 20585, United States.; Data Science and Learning Division, Argonne National Laboratory, Lemont, Illinois 60439, United States.; National Virtual Biotechnology Laboratory, US Department of Energy, Washington, District of Columbia 20585, United States.; Data Science and Learning Division, Argonne National Laboratory, Lemont, Illinois 60439, United States.; Consortium for Advanced Science and Engineering, University of Chicago, Chicago, Illinois 60615, United States.; Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, Tennessee 38163, United States.; National Virtual Biotechnology Laboratory, US Department of Energy, Washington, District of Columbia 20585, United States.; Joint Institute for Biological Sciences, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, United States.; National Virtual Biotechnology Laboratory, US Department of Energy, Washington, District of Columbia 20585, United States.; Second Target Station, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, United States.; Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, DHHS, Bethesda, Maryland 20892-0520, United States.; National Virtual Biotechnology Laboratory, US Department of Energy, Washington, District of Columbia 20585, United States.; Center for Nanophase Materials Sciences, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, United States.; Neutron Scattering Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, United States.; National Virtual Biotechnology Laboratory, US Department of Energy, Washington, District of Columbia 20585, United States.

Creating small-molecule antivirals specific for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins is crucial to battle coronavirus disease 2019 (COVID-19). SARS-CoV-2 main protease (M(pro)) is an established drug target for the design of protease inhibitors. We performed a structure-activity relationship (SAR) study of noncovalent compounds that bind in the enzyme's substrate-binding subsites S1 and S2, revealing structural, electronic, and electrostatic determinants of these sites. The study was guided by the X-ray/neutron structure of M(pro) complexed with Mcule-5948770040 (compound 1), in which protonation states were directly visualized. Virtual reality-assisted structure analysis and small-molecule building were employed to generate analogues of 1. In vitro enzyme inhibition assays and room-temperature X-ray structures demonstrated the effect of chemical modifications on M(pro) inhibition, showing that (1) maintaining correct geometry of an inhibitor's P1