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407. Drug repurposing approach to combating coronavirus: Potential drugs and drug targets.

Author

Xu, Jimin, Xue, Yu, Zhou, Richard, Shi, Pei‐Yong, Li, Hongmin, and Zhou, Jia

Subjects
COVID-19, MERS coronavirus, SARS disease, COVID-19 pandemic, EMERGING infectious diseases
Abstract

In the past two decades, three highly pathogenic human coronaviruses severe acute respiratory syndrome coronavirus (SARS‐CoV), Middle East respiratory syndrome coronavirus, and, recently, SARS‐CoV‐2, have caused pandemics of severe acute respiratory diseases with alarming morbidity and mortality. Due to the lack of specific anti‐CoV therapies, the ongoing pandemic of coronavirus disease 2019 (COVID‐19) poses a great challenge to clinical management and highlights an urgent need for effective interventions. Drug repurposing is a rapid and feasible strategy to identify effective drugs for combating this deadly infection. In this review, we summarize the therapeutic CoV targets, focus on the existing small molecule drugs that have the potential to be repurposed for existing and emerging CoV infections of the future, and discuss the clinical progress of developing small molecule drugs for COVID‐19. [ABSTRACT FROM AUTHOR]

Published
2021
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408. High-Throughput Fitness Profiling of Zika Virus E Protein Reveals Different Roles for Glycosylation during Infection of Mammalian and Mosquito Cells.

Author

Gong, Danyang, Gong, Danyang, Zhang, Tian-Hao, Zhao, Dawei, Du, Yushen, Chapa, Travis J, Shi, Yuan, Wang, Laurie, Contreras, Deisy, Zeng, Gang, Shi, Pei-Yong, Wu, Ting-Ting, Arumugaswami, Vaithilingaraja, Sun, Ren, Gong, Danyang, Gong, Danyang, Zhang, Tian-Hao, Zhao, Dawei, Du, Yushen, Chapa, Travis J, Shi, Yuan, Wang, Laurie, Contreras, Deisy, Zeng, Gang, Shi, Pei-Yong, Wu, Ting-Ting, Arumugaswami, Vaithilingaraja, and Sun, Ren

Abstract

Zika virus (ZIKV) infection causes Guillain-Barré syndrome and severe birth defects. ZIKV envelope (E) protein is the major viral protein involved in cell receptor binding and entry and is therefore considered one of the major determinants in ZIKV pathogenesis. Here we report a gene-wide mapping of functional residues of ZIKV E protein using a mutant library, with changes covering every nucleotide position. By comparing the replication fitness of every viral mutant between mosquito and human cells, we identified that mutations affecting glycosylation display the most divergence. By characterizing individual mutants, we show that ablation of glycosylation selectively benefits ZIKV infection of mosquito cells by enhancing cell entry, whereas it either has little impact on ZIKV infection on certain human cells or leads to decreased infection through the entry factor DC-SIGN. In conclusion, we define the roles of individual residues of ZIKV envelope protein, which contribute to ZIKV replication fitness in human and mosquito cells.

Published
2018

409. Zika virus infection elicits auto-antibodies to C1q

Author

Koma, Takaaki, Veljkovic, Veljko, Anderson, Danielle E., Wang, Lin-Fa, Rossi, Shannan L., Shan, Chao, Shi, Pei-Yong, Beasley, David W., Bukreyeva, Natalya, Smith, Jeanon N., Hallam, Steven, Huang, Cheng, von Messling, Veronika, Paessler, Slobodan, Koma, Takaaki, Veljkovic, Veljko, Anderson, Danielle E., Wang, Lin-Fa, Rossi, Shannan L., Shan, Chao, Shi, Pei-Yong, Beasley, David W., Bukreyeva, Natalya, Smith, Jeanon N., Hallam, Steven, Huang, Cheng, von Messling, Veronika, and Paessler, Slobodan

Abstract

Zika virus (ZIKV) causes mostly asymptomatic infection or mild febrile illness. However, with an increasing number of patients, various clinical features such as microcephaly, Guillain-Barré syndrome and thrombocytopenia have also been reported. To determine which host factors are related to pathogenesis, the E protein of ZIKV was analyzed with the Informational Spectrum Method, which identifies common information encoded by primary structures of the virus and the respective host protein. The data showed that the ZIKV E protein and the complement component C1q cross-spectra are characterized by a single dominant peak at the frequency F = 0.338, suggesting similar biological properties. Indeed, C1q-specific antibodies were detected in sera obtained from mice and monkeys infected with ZIKV. As C1q has been known to be involved not only in immunity, but also in synaptic organization and different autoimmune diseases, a ZIKV-induced anti-C1q antibody response may contribute to the neurological complications. These findings might also be exploited for the design of safe and efficacious vaccines in the future.

Published
2018

410. Zika virus has oncolytic activity against glioblastoma stem cells

Author

Zhu, Zhe, Gorman, Matthew J, McKenzie, Lisa D, Chai, Jiani N, Hubert, Christopher G, Prager, Briana C, Fernandez, Estefania, Richner, Justin M, Zhang, Rong, Shan, Chao, Tycksen, Eric, Wang, Xiuxing, Shi, Pei-Yong, Diamond, Michael S, Rich, Jeremy N, and Chheda, Milan G

Subjects
Immunology, Fluorescent Antibody Technique, Antineoplastic Agents, Inbred C57BL, Medical and Health Sciences, Cell Line, Mice, Experimental, Rare Diseases, Stem Cell Research - Nonembryonic - Human, Neoplasms, Chlorocebus aethiops, Temozolomide, Genetics, Animals, Humans, West Nile Virus, Vero Cells, Cell Proliferation, Cancer, Oncolytic Virotherapy, Tumor, Brain Neoplasms, Neurosciences, Zika Virus, Gene Therapy, Stem Cell Research, Alkylating, Combined Modality Therapy, Brain Disorders, Dacarbazine, Brain Cancer, Orphan Drug, Neoplastic Stem Cells, Female, Stem Cell Research - Nonembryonic - Non-Human, Glioblastoma
Abstract

Glioblastoma is a highly lethal brain cancer that frequently recurs in proximity to the original resection cavity. We explored the use of oncolytic virus therapy against glioblastoma with Zika virus (ZIKV), a flavivirus that induces cell death and differentiation of neural precursor cells in the developing fetus. ZIKV preferentially infected and killed glioblastoma stem cells (GSCs) relative to differentiated tumor progeny or normal neuronal cells. The effects against GSCs were not a general property of neurotropic flaviviruses, as West Nile virus indiscriminately killed both tumor and normal neural cells. ZIKV potently depleted patient-derived GSCs grown in culture and in organoids. Moreover, mice with glioblastoma survived substantially longer and at greater rates when the tumor was inoculated with a mouse-adapted strain of ZIKV. Our results suggest that ZIKV is an oncolytic virus that can preferentially target GSCs; thus, genetically modified strains that further optimize safety could have therapeutic efficacy for adult glioblastoma patients.

Published
2017

411. Vaccine mediated protection against Zika virus-induced congenital disease

Author

Richner, Justin M., Jagger, Brett W., Shan, Chao, Fontes, Camila R., Dowd, Kimberly A., Cao, Bin, Himansu, Sunny, Caine, Elizabeth A., Nunes, Bruno Tardelli Diniz, Medeiros, Daniele Barbosa de Almeida, Muruato, Antonio E., Foreman, Bryant M., Luo, Huanle, Wang, Tian, Barrett, Alan D., Weaver, Scott C., Vasconcelos, Pedro Fernando da Costa, Rossi, Shannan L., Ciaramella, Giuseppe, Mysorekar, Indira U., Pierson, Theodore C., Shi, Pei-Yong, and Diamond, Michael S.

Subjects
Infec??o pelo Zika virus / virologia, Vacinas de Subunidades / imunologia, Vacinas Virais / administra??o & dosagem, Infec??o pelo Zika virus / preven??o & controle, Vacinas de Subunidades / administra??o & dosagem, Vacinas Virais / imunologia, Muta??o, Infec??o pelo Zika virus / imunologia, Feto / virologia, Camundongos Endog?micos C57BL, humanities, Zika virus / fisiologia
Abstract

Washington University School of Medicine. Department of Medicine. St. Louis, MO, USA. Washington University School of Medicine. Department of Medicine. St. Louis, MO, USA. University of Texas Medical Branch. Department of Biochemistry & Molecular Biology. Galveston, TX, USA. University of Texas Medical Branch. Department of Biochemistry & Molecular Biology. Galveston, TX, USA. National Institutes of Health. Laboratory of Viral Diseases. Viral Pathogenesis Section. Bethesda, MD. USA Washington University School of Medicine. Department of Obstetrics and Gynecology. St. Louis, MO, USA. Moderna Venture. Valera LLC. Technology Square. Cambridge, MA, USA. Washington University School of Medicine. Department of Medicine. St. Louis, MO, USA. University of Texas Medical Branch. Department of Biochemistry & Molecular Biology. Galveston, TX, USA / Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. University of Texas Medical Branch. Department of Biochemistry & Molecular Biology. Galveston, TX, USA / Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. University of Texas Medical Branch. Department of Biochemistry & Molecular Biology. Galveston, TX, USA / University of Texas Medical Branch. Department of Pathology. Galveston, TX, USA. National Institutes of Health. Laboratory of Viral Diseases. Viral Pathogenesis Section. Bethesda, MD, USA. University of Texas Medical Branch. Department of Pathology. Galveston, TX, USA. University of Texas Medical Branch. Department of Microbiology and Immunology. Galveston, TX, USA / University of Texas Medical Branch. Sealy Center for Vaccine Development. Galveston, TX, USA. University of Texas Medical Branch. Department of Pathology. Galveston, TX, USA / University of Texas Medical Branch. Sealy Center for Vaccine Development. Galveston, TX, USA. University of Texas Medical Branch. Department of Microbiology and Immunology. Galveston, TX, USA / University of Texas Medical Branch. Institute for Human infections and Immunity. Galveston, TX, USA / University of Texas Medical Branch. Sealy Center for Vaccine Development. Galveston, TX, USA. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil / Par? State University. Department of Pathology. Bel?m, PA, Brazil. University of Texas Medical Branch. Department of Pathology. Galveston, TX, USA / University of Texas Medical Branch. Institute for Human infections and Immunity. Galveston, TX, USA. Moderna Venture. Valera LLC. Technology Square. Cambridge, MA, USA. Washington University School of Medicine. Department of Obstetrics and Gynecology. St. Louis, MO, USA / Washington University School of Medicine. Department of Pathology and Immunology. St. Louis, MO, USA. National Institutes of Health. Laboratory of Viral Diseases. Viral Pathogenesis Section. Bethesda, MD, USA. University of Texas Medical Branch. Department of Biochemistry & Molecular Biology. Galveston, TX, USA / University of Texas Medical Branch. Institute for Translational Science. Galveston, TX, USA / University of Texas Medical Branch. Institute for Human infections and Immunity. Galveston, TX, USA / University of Texas Medical Branch. Department of Pharmacology & Toxicology. Galveston, TX, USA / University of Texas Medical Branch. Sealy Center for Structural Biology & Molecular Biophysics. Galveston, TX, USA. Washington University School of Medicine. Department of Medicine. St. Louis, MO, USA / Washington University School of Medicine. Department of Pathology and Immunology. St. Louis, MO, USA / Washington University School of Medicine. Department of Molecular Microbiology. St. Louis, MO, USA / Washington University School of Medicine. The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs. St. Louis, MO, USA. The emergence of Zika virus (ZIKV) and its association with congenital malformations has prompted the rapid development of vaccines. Although efficacy with multiple viral vaccine platforms has been established in animals, no study has addressed protection during pregnancy. We tested in mice two vaccine platforms, a lipid nanoparticle-encapsulated modified mRNA vaccine encoding ZIKV prM and E genes and a live-attenuated ZIKV strain encoding an NS1 protein without glycosylation, for their ability to protect against transmission to the fetus. Vaccinated dams challenged with a heterologous ZIKV strain at embryo day 6 (E6) and evaluated at E13 showed markedly diminished levels of viral RNA in maternal, placental, and fetal tissues, which resulted in protection against placental damage and fetal demise. As modified mRNA and live-attenuated vaccine platforms can restrict in utero transmission of ZIKV in mice, their further development in humans to prevent congenital ZIKV syndrome is warranted.

Published
2017

412. In vivo monoclonal antibody efficacy against SARS-CoV-2 variant strains

Author

Chen, Rita E., Winkler, Emma S., Case, James Brett, Aziati, Ishmael D., Bricker, Traci L., Joshi, Astha, Darling, Tamarand L., Ying, Baoling, Errico, John M., Shrihari, Swathi, VanBlargan, Laura A., Xie, Xuping, Gilchuk, Pavlo, Zost, Seth J., Droit, Lindsay, Liu, Zhuoming, Stumpf, Spencer, Wang, David, Handley, Scott A., Stine, W. Blaine, Shi, Pei-Yong, Davis-Gardner, Meredith E., Suthar, Mehul S., Knight, Miguel Garcia, Andino, Raul, Chiu, Charles Y., Ellebedy, Ali H., Fremont, Daved H., Whelan, Sean P. J., Crowe, James E., Purcell, Lisa, Corti, Davide, Boon, Adrianus C. M., and Diamond, Michael S.

Abstract

Rapidly emerging SARS-CoV-2 variants jeopardize antibody-based countermeasures. Although cell culture experiments have demonstrated a loss of potency of several anti-spike neutralizing antibodies against variant strains of SARS-CoV-21–3, the in vivo importance of these results remains uncertain. Here we report the in vitro and in vivo activity of a panel of monoclonal antibodies (mAbs), which correspond to many in advanced clinical development by Vir Biotechnology, AbbVie, AstraZeneca, Regeneron and Lilly, against SARS-CoV-2 variant viruses. Although some individual mAbs showed reduced or abrogated neutralizing activity in cell culture against B.1.351, B.1.1.28, B.1.617.1 and B.1.526 viruses with mutations at residue E484 of the spike protein, low prophylactic doses of mAb combinations protected against infection by many variants in K18-hACE2 transgenic mice, 129S2 immunocompetent mice and hamsters, without the emergence of resistance. Exceptions were LY-CoV555 monotherapy and LY-CoV555 and LY-CoV016 combination therapy, both of which lost all protective activity, and the combination of AbbVie 2B04 and 47D11, which showed a partial loss of activity. When administered after infection, higher doses of several mAb cocktails protected in vivo against viruses with a B.1.351 spike gene. Therefore, many—but not all—of the antibody products with Emergency Use Authorization should retain substantial efficacy against the prevailing variant strains of SARS-CoV-2.

Published
2021
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413. Nasal delivery of an IgM offers broad protection from SARS-CoV-2 variants

Author

Ku, Zhiqiang, Xie, Xuping, Hinton, Paul R., Liu, Xinli, Ye, Xiaohua, Muruato, Antonio E., Ng, Dean C., Biswas, Sujit, Zou, Jing, Liu, Yang, Pandya, Deepal, Menachery, Vineet D., Rahman, Sachi, Cao, Yu-An, Deng, Hui, Xiong, Wei, Carlin, Kevin B., Liu, Junquan, Su, Hang, Haanes, Elizabeth J., Keyt, Bruce A., Zhang, Ningyan, Carroll, Stephen F., Shi, Pei-Yong, and An, Zhiqiang

Abstract

Resistance represents a major challenge for antibody-based therapy for COVID-191–4. Here we engineered an immunoglobulin M (IgM) neutralizing antibody (IgM-14) to overcome the resistance encountered by immunoglobulin G (IgG)-based therapeutics. IgM-14 is over 230-fold more potent than its parental IgG-14 in neutralizing SARS-CoV-2. IgM-14 potently neutralizes the resistant virus raised by its corresponding IgG-14, three variants of concern—B.1.1.7 (Alpha, which first emerged in the UK), P.1 (Gamma, which first emerged in Brazil) and B.1.351 (Beta, which first emerged in South Africa)—and 21 other receptor-binding domain mutants, many of which are resistant to the IgG antibodies that have been authorized for emergency use. Although engineering IgG into IgM enhances antibody potency in general, selection of an optimal epitope is critical for identifying the most effective IgM that can overcome resistance. In mice, a single intranasal dose of IgM-14 at 0.044 mg per kg body weight confers prophylactic efficacy and a single dose at 0.4 mg per kg confers therapeutic efficacy against SARS-CoV-2. IgM-14, but not IgG-14, also confers potent therapeutic protection against the P.1 and B.1.351 variants. IgM-14 exhibits desirable pharmacokinetics and safety profiles when administered intranasally in rodents. Our results show that intranasal administration of an engineered IgM can improve efficacy, reduce resistance and simplify the prophylactic and therapeutic treatment of COVID-19.

Published
2021
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414. Zika Virus Epidemic in Brazil. II. Post-Mortem Analyses of Neonates with Microcephaly, Stillbirths, and Miscarriage

Author

Azevedo, Raimunda S.S., primary, Araujo, Marialva T., additional, Oliveira, Consuelo S., additional, Filho, Arnaldo Jorge Martins, additional, Nunes, Bruno T.D., additional, Henriques, Daniele F., additional, Silva, Eliana V.P., additional, Carvalho, Valéria L., additional, Chiang, Jannifer O., additional, Martins, Lívia C., additional, Vasconcelos, Barbara C.B., additional, Sousa, Jorge R., additional, Araujo, Fernanda Montenegro C., additional, Ribeiro, Erlane M., additional, Castro, Andrezza R.P., additional, de Queiroz, Maria G. L., additional, Verotti, Mariana P., additional, Nunes, Márcio R.T., additional, Cruz, Ana C.R., additional, Rodrigues, Sueli G., additional, Shi, Pei-Yong, additional, Quaresma, Juarez A.S., additional, Tesh, Robert B., additional, and Vasconcelos, Pedro F.C., additional

Published
2018
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415. Treatment of Human Glioblastoma with a Live Attenuated Zika Virus Vaccine Candidate

Author

Chen, Qi, primary, Wu, Jin, additional, Ye, Qing, additional, Ma, Feng, additional, Zhu, Qian, additional, Wu, Yan, additional, Shan, Chao, additional, Xie, Xuping, additional, Li, Dapei, additional, Zhan, Xiaoyan, additional, Li, Chunfeng, additional, Li, Xiao-Feng, additional, Qin, Xiaoling, additional, Zhao, Tongyan, additional, Wu, Haitao, additional, Shi, Pei-Yong, additional, Man, Jianghong, additional, and Qin, Cheng-Feng, additional

Published
2018
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421. A Single-Dose Live-Attenuated Zika Virus Vaccine with Controlled Infection Rounds that Protects against Vertical Transmission

Author

Xie, Xuping, primary, Kum, Dieudonné B., additional, Xia, Hongjie, additional, Luo, Huanle, additional, Shan, Chao, additional, Zou, Jing, additional, Muruato, Antonio E., additional, Medeiros, Daniele B.A., additional, Nunes, Bruno T.D., additional, Dallmeier, Kai, additional, Rossi, Shannan L., additional, Weaver, Scott C., additional, Neyts, Johan, additional, Wang, Tian, additional, Vasconcelos, Pedro F.C., additional, and Shi, Pei-Yong, additional

Published
2018
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423. Peli1 facilitates virus replication and promotes neuroinflammation during West Nile virus infection

Author

Luo, Huanle, primary, Winkelmann, Evandro R., additional, Zhu, Shuang, additional, Ru, Wenjuan, additional, Mays, Elizabeth, additional, Silvas, Jesus A., additional, Vollmer, Lauren L., additional, Gao, Junling, additional, Peng, Bi-Hung, additional, Bopp, Nathen E., additional, Cromer, Courtney, additional, Shan, Chao, additional, Xie, Guorui, additional, Li, Guangyu, additional, Tesh, Robert, additional, Popov, Vsevolod L., additional, Shi, Pei-Yong, additional, Sun, Shao-Cong, additional, Wu, Ping, additional, Klein, Robyn S., additional, Tang, Shao-Jun, additional, Zhang, Wenbo, additional, Aguilar, Patricia V., additional, and Wang, Tian, additional

Published
2018
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424. A Zika virus vaccine expressing premembrane-envelope-NS1 polyprotein

Author

Li, Anzhong, primary, Yu, Jingyou, additional, Lu, Mijia, additional, Ma, Yuanmei, additional, Attia, Zayed, additional, Shan, Chao, additional, Xue, Miaoge, additional, Liang, Xueya, additional, Craig, Kelsey, additional, Makadiya, Nirajkumar, additional, He, Jennifer J., additional, Jennings, Ryan, additional, Shi, Pei-Yong, additional, Peeples, Mark E., additional, Liu, Shan-Lu, additional, Boyaka, Prosper N., additional, and Li, Jianrong, additional

Published
2018
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427. Human IFIT3 Modulates IFIT1 RNA Binding Specificity and Protein Stability

Author

Johnson, Britney, primary, VanBlargan, Laura A., additional, Xu, Wei, additional, White, James P., additional, Shan, Chao, additional, Shi, Pei-Yong, additional, Zhang, Rong, additional, Adhikari, Jagat, additional, Gross, Michael L., additional, Leung, Daisy W., additional, Diamond, Michael S., additional, and Amarasinghe, Gaya K., additional

Published
2018
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428. High-Throughput Fitness Profiling of Zika Virus E Protein Reveals Different Roles for Glycosylation during Infection of Mammalian and Mosquito Cells

Author

Gong, Danyang, primary, Zhang, Tian-Hao, additional, Zhao, Dawei, additional, Du, Yushen, additional, Chapa, Travis J., additional, Shi, Yuan, additional, Wang, Laurie, additional, Contreras, Deisy, additional, Zeng, Gang, additional, Shi, Pei-Yong, additional, Wu, Ting-Ting, additional, Arumugaswami, Vaithilingaraja, additional, and Sun, Ren, additional

Published
2018
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429. Development of a chimeric Zika vaccine using a licensed live-attenuated flavivirus vaccine as backbone

Author

Li, Xiao-Feng, primary, Dong, Hao-Long, additional, Wang, Hong-Jiang, additional, Huang, Xing-Yao, additional, Qiu, Ye-Feng, additional, Ji, Xue, additional, Ye, Qing, additional, Li, Chunfeng, additional, Liu, Yang, additional, Deng, Yong-Qiang, additional, Jiang, Tao, additional, Cheng, Gong, additional, Zhang, Fu-Chun, additional, Davidson, Andrew D., additional, Song, Ya-Jun, additional, Shi, Pei-Yong, additional, and Qin, Cheng-Feng, additional

Published
2018
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431. Zika virus infection elicits auto-antibodies to C1q

Author

Koma, Takaaki, primary, Veljkovic, Veljko, additional, Anderson, Danielle E., additional, Wang, Lin-Fa, additional, Rossi, Shannan L., additional, Shan, Chao, additional, Shi, Pei-Yong, additional, Beasley, David W., additional, Bukreyeva, Natalya, additional, Smith, Jeanon N., additional, Hallam, Steven, additional, Huang, Cheng, additional, von Messling, Veronika, additional, and Paessler, Slobodan, additional

Published
2018
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432. An evolutionary NS1 mutation enhances Zika virus evasion of host interferon induction

Author

Xia, Hongjie, primary, Luo, Huanle, additional, Shan, Chao, additional, Muruato, Antonio E., additional, Nunes, Bruno T. D., additional, Medeiros, Daniele B. A., additional, Zou, Jing, additional, Xie, Xuping, additional, Giraldo, Maria Isabel, additional, Vasconcelos, Pedro F. C., additional, Weaver, Scott C., additional, Wang, Tian, additional, Rajsbaum, Ricardo, additional, and Shi, Pei-Yong, additional

Published
2018
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435. Characterization of a candidate tetravalent vaccine based on 2'-O-methyltransferase mutants

Author

Züst, Roland, primary, Li, Shi-Hua, additional, Xie, Xuping, additional, Velumani, Sumathy, additional, Chng, Melissa, additional, Toh, Ying-Xiu, additional, Zou, Jing, additional, Dong, Hongping, additional, Shan, Chao, additional, Pang, Jassia, additional, Qin, Cheng-Feng, additional, Newell, Evan W., additional, Shi, Pei-Yong, additional, and Fink, Katja, additional

Published
2018
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438. Spike mutation D614G alters SARS-CoV-2 fitness

Author

Plante, Jessica A., Liu, Yang, Liu, Jianying, Xia, Hongjie, Johnson, Bryan A., Lokugamage, Kumari G., Zhang, Xianwen, Muruato, Antonio E., Zou, Jing, Fontes-Garfias, Camila R., Mirchandani, Divya, Scharton, Dionna, Bilello, John P., Ku, Zhiqiang, An, Zhiqiang, Kalveram, Birte, Freiberg, Alexander N., Menachery, Vineet D., Xie, Xuping, Plante, Kenneth S., Weaver, Scott C., and Shi, Pei-Yong

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein substitution D614G became dominant during the coronavirus disease 2019 (COVID-19) pandemic1,2. However, the effect of this variant on viral spread and vaccine efficacy remains to be defined. Here we engineered the spike D614G substitution in the USA-WA1/2020 SARS-CoV-2 strain, and found that it enhances viral replication in human lung epithelial cells and primary human airway tissues by increasing the infectivity and stability of virions. Hamsters infected with SARS-CoV-2 expressing spike(D614G) (G614 virus) produced higher infectious titres in nasal washes and the trachea, but not in the lungs, supporting clinical evidence showing that the mutation enhances viral loads in the upper respiratory tract of COVID-19 patients and may increase transmission. Sera from hamsters infected with D614 virus exhibit modestly higher neutralization titres against G614 virus than against D614 virus, suggesting that the mutation is unlikely to reduce the ability of vaccines in clinical trials to protect against COVID-19, and that therapeutic antibodies should be tested against the circulating G614 virus. Together with clinical findings, our work underscores the importance of this variant in viral spread and its implications for vaccine efficacy and antibody therapy.

Published
2021
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439. The role of sequence context, nucleotide pool balance and stress in 2′-deoxynucleotide misincorporation in viral, bacterial and mammalian RNA

Author

Massachusetts Institute of Technology. Center for Environmental Health Sciences, Massachusetts Institute of Technology. Department of Biological Engineering, Dedon, Peter C, Wang, Jin, Dong, Hongping, Chionh, Yok Hian, McBee, Megan E., Sirirungruang, Sasilada, Cunningham, Richard P., Shi, Pei-Yong, Massachusetts Institute of Technology. Center for Environmental Health Sciences, Massachusetts Institute of Technology. Department of Biological Engineering, Dedon, Peter C, Wang, Jin, Dong, Hongping, Chionh, Yok Hian, McBee, Megan E., Sirirungruang, Sasilada, Cunningham, Richard P., and Shi, Pei-Yong

Abstract

The misincorporation of 2′-deoxyribonucleotides (dNs) into RNA has important implications for the function of non-coding RNAs, the translational fidelity of coding RNAs and the mutagenic evolution of viral RNA genomes. However, quantitative appreciation for the degree to which dN misincorporation occurs is limited by the lack of analytical tools. Here, we report a method to hydrolyze RNA to release 2′-deoxyribonucleotide-ribonucleotide pairs (dNrN) that are then quantified by chromatography-coupled mass spectrometry (LC-MS). Using this platform, we found misincorporated dNs occurring at 1 per 10[superscript 3] to 10[superscript 5] ribonucleotide (nt) in mRNA, rRNAs and tRNA in human cells, Escherichia coli, Saccharomyces cerevisiae and, most abundantly, in the RNA genome of dengue virus. The frequency of dNs varied widely among organisms and sequence contexts, and partly reflected the in vitro discrimination efficiencies of different RNA polymerases against 2′-deoxyribonucleoside 5′-triphosphates (dNTPs). Further, we demonstrate a strong link between dN frequencies in RNA and the balance of dNTPs and ribonucleoside 5′-triphosphates (rNTPs) in the cellular pool, with significant stress-induced variation of dN incorporation. Potential implications of dNs in RNA are discussed, including the possibilities of dN incorporation in RNA as a contributing factor in viral evolution and human disease, and as a host immune defense mechanism against viral infections., National Institutes of Health (U.S.) (Grant ES022858), Singapore. National Research Foundation, Singapore-MIT Alliance for Research and Technology

Published
2017

440. Zika virus: diagnosis, therapeutics, and vaccine

Author

Shan, Chao, Xie, Xuping, Barrett, Alan D. T, Garcia-Blanco, Mariano A, Tesh, Robert B, Vasconcelos, Pedro Fernando da Costa, Vasilakis, Nikos, Weaver, Scott C, and Shi, Pei-Yong

Subjects
Infec??o pelo Zika virus / diagn?stico, Infec??o pelo Zika virus / preven??o & controle, Vacinas Virais, Infec??o pelo Zika virus / terapia, Infec??o pelo Zika virus / imunologia, humanities
Abstract

University of Texas Medical Branch. Department of Biochemistry & Molecular Biology. Department of Phamarcology & Toxicology. Sealy Center for Structural Biology & Molecular Biophysics. Galveston, Texas, USA. University of Texas Medical Branch. Department of Biochemistry & Molecular Biology. Department of Phamarcology & Toxicology. Sealy Center for Structural Biology & Molecular Biophysics. Galveston, Texas, USA. University of Texas Medical Branch. Department of Microbiology & Immunology. Department of Pathology. Sealy Center for Vaccine Development. Galveston, Texas, USA. University of Texas Medical Branch. Department of Biochemistry & Molecular Biology. Department of Phamarcology & Toxicology. Sealy Center for Structural Biology & Molecular Biophysics. Galveston, Texas, USA. University of Texas Medical Branch. Department of Microbiology & Immunology. Department of Pathology. Galveston, Texas, USA / University of Texas Medical Branch. Institute for Human Infections and Immunity. Galveston, Texas, USA. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. University of Texas Medical Branch. Department of Microbiology & Immunology. Department of Pathology. Galveston, Texas, USA / University of Texas Medical Branch. Institute for Human Infections and Immunity. Galveston, Texas, USA. University of Texas Medical Branch. Department of Microbiology & Immunology. Department of Pathology. Galveston, Texas, USA / University of Texas Medical Branch. Institute for Human Infections and Immunity. Galveston, Texas, USA. University of Texas Medical Branch. Department of Biochemistry & Molecular Biology. Department of Phamarcology & Toxicology. Sealy Center for Structural Biology & Molecular Biophysics. Galveston, Texas, USA. The current explosive epidemic of Zika virus in South and Central America, as well as the Caribbean, poses a global public health emergency. Here we comment on the challenges on development of better diagnosis and potential therapeutics and vaccine for Zika virus.

Published
2016

442. BNT162b2-elicited neutralization of B.1.617 and other SARS-CoV-2 variants.

Author

Liu, Jianying, Liu, Yang, Xia, Hongjie, Zou, Jing, Weaver, Scott C., Swanson, Kena A., Cai, Hui, Cutler, Mark, Cooper, David, Muik, Alexander, Jansen, Kathrin U., Sahin, Ugur, Xie, Xuping, Dormitzer, Philip R., and Shi, Pei-Yong

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuing to evolve around the world, generating new variants that are of concern on the basis of their potential for altered transmissibility, pathogenicity, and coverage by vaccines and therapeutic agents1–5. Here we show that serum samples taken from twenty human volunteers, two or four weeks after their second dose of the BNT162b2 vaccine, neutralize engineered SARS-CoV-2 with a USA-WA1/2020 genetic background (a virus strain isolated in January 2020) and spike glycoproteins from the recently identified B.1.617.1, B.1.617.2, B.1.618 (all of which were first identified in India) or B.1.525 (first identified in Nigeria) lineages. Geometric mean plaque reduction neutralization titres against the variant viruses—particularly the B.1.617.1 variant—seemed to be lower than the titre against the USA-WA1/2020 virus, but all sera tested neutralized the variant viruses at titres of at least 1:40. The susceptibility of the variant strains to neutralization elicited by the BNT162b2 vaccine supports mass immunization as a central strategy to end the coronavirus disease 2019 (COVID-19) pandemic globally.Samples of serum from individuals immunized with the BNT162b2 vaccine show neutralization activity against engineered SARS-CoV-2s bearing the spike mutations from B.1.617 and other variants. [ABSTRACT FROM AUTHOR]

Published
2021
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443. A single mutation in the prM protein of Zika virus contributes to fetal microcephaly

Author

Yuan, Ling, primary, Huang, Xing-Yao, additional, Liu, Zhong-Yu, additional, Zhang, Feng, additional, Zhu, Xing-Liang, additional, Yu, Jiu-Yang, additional, Ji, Xue, additional, Xu, Yan-Peng, additional, Li, Guanghui, additional, Li, Cui, additional, Wang, Hong-Jiang, additional, Deng, Yong-Qiang, additional, Wu, Menghua, additional, Cheng, Meng-Li, additional, Ye, Qing, additional, Xie, Dong-Yang, additional, Li, Xiao-Feng, additional, Wang, Xiangxi, additional, Shi, Weifeng, additional, Hu, Baoyang, additional, Shi, Pei-Yong, additional, Xu, Zhiheng, additional, and Qin, Cheng-Feng, additional

Published
2017
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445. High-throughput fitness profiling of Zika virus E protein reveals different roles for N-linked glycosylation during infection of mammalian and mosquito cells

Author

Gong, Danyang, primary, Zhang, Tian-hao, additional, Zhao, Dawei, additional, Du, Yushen, additional, Chapa, Travis J., additional, Shi, Yuan, additional, Wang, Laurie, additional, Contreras, Deisy, additional, Zeng, Gang, additional, Shi, Pei-yong, additional, Wu, Ting-Ting, additional, Arumugaswami, Vaithilingaraja, additional, and Sun, Ren, additional

Published
2017
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447. Functional Analysis of Glycosylation of Zika Virus Envelope Protein

Author

Fontes-Garfias, Camila R., primary, Shan, Chao, additional, Luo, Huanle, additional, Muruato, Antonio E., additional, Medeiros, Daniele B.A., additional, Mays, Elizabeth, additional, Xie, Xuping, additional, Zou, Jing, additional, Roundy, Christopher M., additional, Wakamiya, Maki, additional, Rossi, Shannan L., additional, Wang, Tian, additional, Weaver, Scott C., additional, and Shi, Pei-Yong, additional

Published
2017
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448. A single-dose live-attenuated vaccine prevents Zika virus pregnancy transmission and testis damage

Author

Shan, Chao, primary, Muruato, Antonio E., additional, Jagger, Brett W., additional, Richner, Justin, additional, Nunes, Bruno T. D., additional, Medeiros, Daniele B. A., additional, Xie, Xuping, additional, Nunes, Jannyce G. C., additional, Morabito, Kaitlyn M., additional, Kong, Wing-Pui, additional, Pierson, Theodore C., additional, Barrett, Alan D., additional, Weaver, Scott C., additional, Rossi, Shannan L., additional, Vasconcelos, Pedro F. C., additional, Graham, Barney S., additional, Diamond, Michael S., additional, and Shi, Pei-Yong, additional

Published
2017
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450. Correction: Zika virus has oncolytic activity against glioblastoma stem cells

Author

Zhu, Zhe, primary, Gorman, Matthew J., additional, McKenzie, Lisa D., additional, Chai, Jiani N., additional, Hubert, Christopher G., additional, Prager, Briana C., additional, Fernandez, Estefania, additional, Richner, Justin M., additional, Zhang, Rong, additional, Shan, Chao, additional, Tycksen, Eric, additional, Wang, Xiuxing, additional, Shi, Pei-Yong, additional, Diamond, Michael S., additional, Rich, Jeremy N., additional, and Chheda, Milan G., additional

Published
2017
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